bull Practical basics for most common substances of abuse
bull Key concepts to know in any medical practice
bull Preparation for the board exams Steps 2-3
Addiction ndash As a Brain Disorder
bull Studies of twins adoptees and family cohorts suggest that genetic factors contribute to approximately 50-60 of the variability in the risk for addiction
bull Predictable and persistent structural and functional brain changes are seen
bull More focus on genetics on boards each year Orbitofrontal Cortex
Addiction as a Complex Biopsychosocial Disorder
bull ldquoIt is impossible to understand addiction without asking what relief the addict finds or hopes to find in the drug or the addictive behaviorrdquo Gabor Mate MD
bull Higher rates of addiction in patients with chronic pain psychiatric disorders history of trauma and raised in homes with substance abuse
response to treatment are similar to other chronic diseases (HTN DMII and Asthma)
bull Relapse is commonbull 40-60 of patients treated for a SUD return to
regular use within a year following treatment
Approach
bull Non-judgmental and compassionatendash ldquoTell me about your alcohol (or drug use)rdquondash Discussing their past use can make it easierndash Patients are often embarrassed and vulnerable
bull 75 of primary care patients who screened positive for alcohol misuse showed motivation to change This increased as the severity went up
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
bull Mouse Party ndash (httplearngeneticsutaheducontentaddictionmouse)
Increases over Time in the Potency of Tetrahydrocannabinol (THC) in Marijuana and the Number of Emergency Department Visits Involving Marijuana Cocaine or Heroin
Volkow ND et al N Engl J Med 20143702219-2227
Use of Marijuana in Relation to Perceived Risk and Daily Use of Tobacco Cigarettes or Marijuana among US Students in Grade 12 1975ndash2013
Volkow ND et al N Engl J Med 20143702219-2227
Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana
Volkow ND et al N Engl J Med 20143702219-2227
Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being
Volkow ND et al N Engl J Med 20143702219-2227
A 42 yo man with schizophrenia presents to the ED after being found yelling at cars in traffic On
interview the patient has AVH paranoia and persecutorial delusions Initial toxicology
screening shows only cannabis in urine Patientrsquos only medication is Risperidone Consta 50mg IM q2weeks You call the patientrsquos case manager to
get a sense of baseline Case manager states that current symptoms are clearly worse than usual Chose the correct statement regarding
the case above
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Goals for today
bull Practical basics for most common substances of abuse
bull Key concepts to know in any medical practice
bull Preparation for the board exams Steps 2-3
Addiction ndash As a Brain Disorder
bull Studies of twins adoptees and family cohorts suggest that genetic factors contribute to approximately 50-60 of the variability in the risk for addiction
bull Predictable and persistent structural and functional brain changes are seen
bull More focus on genetics on boards each year Orbitofrontal Cortex
Addiction as a Complex Biopsychosocial Disorder
bull ldquoIt is impossible to understand addiction without asking what relief the addict finds or hopes to find in the drug or the addictive behaviorrdquo Gabor Mate MD
bull Higher rates of addiction in patients with chronic pain psychiatric disorders history of trauma and raised in homes with substance abuse
response to treatment are similar to other chronic diseases (HTN DMII and Asthma)
bull Relapse is commonbull 40-60 of patients treated for a SUD return to
regular use within a year following treatment
Approach
bull Non-judgmental and compassionatendash ldquoTell me about your alcohol (or drug use)rdquondash Discussing their past use can make it easierndash Patients are often embarrassed and vulnerable
bull 75 of primary care patients who screened positive for alcohol misuse showed motivation to change This increased as the severity went up
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
bull Mouse Party ndash (httplearngeneticsutaheducontentaddictionmouse)
Increases over Time in the Potency of Tetrahydrocannabinol (THC) in Marijuana and the Number of Emergency Department Visits Involving Marijuana Cocaine or Heroin
Volkow ND et al N Engl J Med 20143702219-2227
Use of Marijuana in Relation to Perceived Risk and Daily Use of Tobacco Cigarettes or Marijuana among US Students in Grade 12 1975ndash2013
Volkow ND et al N Engl J Med 20143702219-2227
Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana
Volkow ND et al N Engl J Med 20143702219-2227
Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being
Volkow ND et al N Engl J Med 20143702219-2227
A 42 yo man with schizophrenia presents to the ED after being found yelling at cars in traffic On
interview the patient has AVH paranoia and persecutorial delusions Initial toxicology
screening shows only cannabis in urine Patientrsquos only medication is Risperidone Consta 50mg IM q2weeks You call the patientrsquos case manager to
get a sense of baseline Case manager states that current symptoms are clearly worse than usual Chose the correct statement regarding
the case above
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Addiction ndash As a Brain Disorder
bull Studies of twins adoptees and family cohorts suggest that genetic factors contribute to approximately 50-60 of the variability in the risk for addiction
bull Predictable and persistent structural and functional brain changes are seen
bull More focus on genetics on boards each year Orbitofrontal Cortex
Addiction as a Complex Biopsychosocial Disorder
bull ldquoIt is impossible to understand addiction without asking what relief the addict finds or hopes to find in the drug or the addictive behaviorrdquo Gabor Mate MD
bull Higher rates of addiction in patients with chronic pain psychiatric disorders history of trauma and raised in homes with substance abuse
response to treatment are similar to other chronic diseases (HTN DMII and Asthma)
bull Relapse is commonbull 40-60 of patients treated for a SUD return to
regular use within a year following treatment
Approach
bull Non-judgmental and compassionatendash ldquoTell me about your alcohol (or drug use)rdquondash Discussing their past use can make it easierndash Patients are often embarrassed and vulnerable
bull 75 of primary care patients who screened positive for alcohol misuse showed motivation to change This increased as the severity went up
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
bull Mouse Party ndash (httplearngeneticsutaheducontentaddictionmouse)
Increases over Time in the Potency of Tetrahydrocannabinol (THC) in Marijuana and the Number of Emergency Department Visits Involving Marijuana Cocaine or Heroin
Volkow ND et al N Engl J Med 20143702219-2227
Use of Marijuana in Relation to Perceived Risk and Daily Use of Tobacco Cigarettes or Marijuana among US Students in Grade 12 1975ndash2013
Volkow ND et al N Engl J Med 20143702219-2227
Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana
Volkow ND et al N Engl J Med 20143702219-2227
Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being
Volkow ND et al N Engl J Med 20143702219-2227
A 42 yo man with schizophrenia presents to the ED after being found yelling at cars in traffic On
interview the patient has AVH paranoia and persecutorial delusions Initial toxicology
screening shows only cannabis in urine Patientrsquos only medication is Risperidone Consta 50mg IM q2weeks You call the patientrsquos case manager to
get a sense of baseline Case manager states that current symptoms are clearly worse than usual Chose the correct statement regarding
the case above
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Addiction as a Complex Biopsychosocial Disorder
bull ldquoIt is impossible to understand addiction without asking what relief the addict finds or hopes to find in the drug or the addictive behaviorrdquo Gabor Mate MD
bull Higher rates of addiction in patients with chronic pain psychiatric disorders history of trauma and raised in homes with substance abuse
response to treatment are similar to other chronic diseases (HTN DMII and Asthma)
bull Relapse is commonbull 40-60 of patients treated for a SUD return to
regular use within a year following treatment
Approach
bull Non-judgmental and compassionatendash ldquoTell me about your alcohol (or drug use)rdquondash Discussing their past use can make it easierndash Patients are often embarrassed and vulnerable
bull 75 of primary care patients who screened positive for alcohol misuse showed motivation to change This increased as the severity went up
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
bull Mouse Party ndash (httplearngeneticsutaheducontentaddictionmouse)
Increases over Time in the Potency of Tetrahydrocannabinol (THC) in Marijuana and the Number of Emergency Department Visits Involving Marijuana Cocaine or Heroin
Volkow ND et al N Engl J Med 20143702219-2227
Use of Marijuana in Relation to Perceived Risk and Daily Use of Tobacco Cigarettes or Marijuana among US Students in Grade 12 1975ndash2013
Volkow ND et al N Engl J Med 20143702219-2227
Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana
Volkow ND et al N Engl J Med 20143702219-2227
Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being
Volkow ND et al N Engl J Med 20143702219-2227
A 42 yo man with schizophrenia presents to the ED after being found yelling at cars in traffic On
interview the patient has AVH paranoia and persecutorial delusions Initial toxicology
screening shows only cannabis in urine Patientrsquos only medication is Risperidone Consta 50mg IM q2weeks You call the patientrsquos case manager to
get a sense of baseline Case manager states that current symptoms are clearly worse than usual Chose the correct statement regarding
the case above
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
response to treatment are similar to other chronic diseases (HTN DMII and Asthma)
bull Relapse is commonbull 40-60 of patients treated for a SUD return to
regular use within a year following treatment
Approach
bull Non-judgmental and compassionatendash ldquoTell me about your alcohol (or drug use)rdquondash Discussing their past use can make it easierndash Patients are often embarrassed and vulnerable
bull 75 of primary care patients who screened positive for alcohol misuse showed motivation to change This increased as the severity went up
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
bull Mouse Party ndash (httplearngeneticsutaheducontentaddictionmouse)
Increases over Time in the Potency of Tetrahydrocannabinol (THC) in Marijuana and the Number of Emergency Department Visits Involving Marijuana Cocaine or Heroin
Volkow ND et al N Engl J Med 20143702219-2227
Use of Marijuana in Relation to Perceived Risk and Daily Use of Tobacco Cigarettes or Marijuana among US Students in Grade 12 1975ndash2013
Volkow ND et al N Engl J Med 20143702219-2227
Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana
Volkow ND et al N Engl J Med 20143702219-2227
Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being
Volkow ND et al N Engl J Med 20143702219-2227
A 42 yo man with schizophrenia presents to the ED after being found yelling at cars in traffic On
interview the patient has AVH paranoia and persecutorial delusions Initial toxicology
screening shows only cannabis in urine Patientrsquos only medication is Risperidone Consta 50mg IM q2weeks You call the patientrsquos case manager to
get a sense of baseline Case manager states that current symptoms are clearly worse than usual Chose the correct statement regarding
the case above
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Approach
bull Non-judgmental and compassionatendash ldquoTell me about your alcohol (or drug use)rdquondash Discussing their past use can make it easierndash Patients are often embarrassed and vulnerable
bull 75 of primary care patients who screened positive for alcohol misuse showed motivation to change This increased as the severity went up
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
bull Mouse Party ndash (httplearngeneticsutaheducontentaddictionmouse)
Increases over Time in the Potency of Tetrahydrocannabinol (THC) in Marijuana and the Number of Emergency Department Visits Involving Marijuana Cocaine or Heroin
Volkow ND et al N Engl J Med 20143702219-2227
Use of Marijuana in Relation to Perceived Risk and Daily Use of Tobacco Cigarettes or Marijuana among US Students in Grade 12 1975ndash2013
Volkow ND et al N Engl J Med 20143702219-2227
Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana
Volkow ND et al N Engl J Med 20143702219-2227
Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being
Volkow ND et al N Engl J Med 20143702219-2227
A 42 yo man with schizophrenia presents to the ED after being found yelling at cars in traffic On
interview the patient has AVH paranoia and persecutorial delusions Initial toxicology
screening shows only cannabis in urine Patientrsquos only medication is Risperidone Consta 50mg IM q2weeks You call the patientrsquos case manager to
get a sense of baseline Case manager states that current symptoms are clearly worse than usual Chose the correct statement regarding
the case above
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
bull Mouse Party ndash (httplearngeneticsutaheducontentaddictionmouse)
Increases over Time in the Potency of Tetrahydrocannabinol (THC) in Marijuana and the Number of Emergency Department Visits Involving Marijuana Cocaine or Heroin
Volkow ND et al N Engl J Med 20143702219-2227
Use of Marijuana in Relation to Perceived Risk and Daily Use of Tobacco Cigarettes or Marijuana among US Students in Grade 12 1975ndash2013
Volkow ND et al N Engl J Med 20143702219-2227
Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana
Volkow ND et al N Engl J Med 20143702219-2227
Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being
Volkow ND et al N Engl J Med 20143702219-2227
A 42 yo man with schizophrenia presents to the ED after being found yelling at cars in traffic On
interview the patient has AVH paranoia and persecutorial delusions Initial toxicology
screening shows only cannabis in urine Patientrsquos only medication is Risperidone Consta 50mg IM q2weeks You call the patientrsquos case manager to
get a sense of baseline Case manager states that current symptoms are clearly worse than usual Chose the correct statement regarding
the case above
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Cannabis
Mechanism of Action
bull Mouse Party ndash (httplearngeneticsutaheducontentaddictionmouse)
Increases over Time in the Potency of Tetrahydrocannabinol (THC) in Marijuana and the Number of Emergency Department Visits Involving Marijuana Cocaine or Heroin
Volkow ND et al N Engl J Med 20143702219-2227
Use of Marijuana in Relation to Perceived Risk and Daily Use of Tobacco Cigarettes or Marijuana among US Students in Grade 12 1975ndash2013
Volkow ND et al N Engl J Med 20143702219-2227
Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana
Volkow ND et al N Engl J Med 20143702219-2227
Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being
Volkow ND et al N Engl J Med 20143702219-2227
A 42 yo man with schizophrenia presents to the ED after being found yelling at cars in traffic On
interview the patient has AVH paranoia and persecutorial delusions Initial toxicology
screening shows only cannabis in urine Patientrsquos only medication is Risperidone Consta 50mg IM q2weeks You call the patientrsquos case manager to
get a sense of baseline Case manager states that current symptoms are clearly worse than usual Chose the correct statement regarding
the case above
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Mechanism of Action
bull Mouse Party ndash (httplearngeneticsutaheducontentaddictionmouse)
Increases over Time in the Potency of Tetrahydrocannabinol (THC) in Marijuana and the Number of Emergency Department Visits Involving Marijuana Cocaine or Heroin
Volkow ND et al N Engl J Med 20143702219-2227
Use of Marijuana in Relation to Perceived Risk and Daily Use of Tobacco Cigarettes or Marijuana among US Students in Grade 12 1975ndash2013
Volkow ND et al N Engl J Med 20143702219-2227
Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana
Volkow ND et al N Engl J Med 20143702219-2227
Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being
Volkow ND et al N Engl J Med 20143702219-2227
A 42 yo man with schizophrenia presents to the ED after being found yelling at cars in traffic On
interview the patient has AVH paranoia and persecutorial delusions Initial toxicology
screening shows only cannabis in urine Patientrsquos only medication is Risperidone Consta 50mg IM q2weeks You call the patientrsquos case manager to
get a sense of baseline Case manager states that current symptoms are clearly worse than usual Chose the correct statement regarding
the case above
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Increases over Time in the Potency of Tetrahydrocannabinol (THC) in Marijuana and the Number of Emergency Department Visits Involving Marijuana Cocaine or Heroin
Volkow ND et al N Engl J Med 20143702219-2227
Use of Marijuana in Relation to Perceived Risk and Daily Use of Tobacco Cigarettes or Marijuana among US Students in Grade 12 1975ndash2013
Volkow ND et al N Engl J Med 20143702219-2227
Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana
Volkow ND et al N Engl J Med 20143702219-2227
Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being
Volkow ND et al N Engl J Med 20143702219-2227
A 42 yo man with schizophrenia presents to the ED after being found yelling at cars in traffic On
interview the patient has AVH paranoia and persecutorial delusions Initial toxicology
screening shows only cannabis in urine Patientrsquos only medication is Risperidone Consta 50mg IM q2weeks You call the patientrsquos case manager to
get a sense of baseline Case manager states that current symptoms are clearly worse than usual Chose the correct statement regarding
the case above
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Totally safe
Increases over Time in the Potency of Tetrahydrocannabinol (THC) in Marijuana and the Number of Emergency Department Visits Involving Marijuana Cocaine or Heroin
Volkow ND et al N Engl J Med 20143702219-2227
Use of Marijuana in Relation to Perceived Risk and Daily Use of Tobacco Cigarettes or Marijuana among US Students in Grade 12 1975ndash2013
Volkow ND et al N Engl J Med 20143702219-2227
Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana
Volkow ND et al N Engl J Med 20143702219-2227
Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being
Volkow ND et al N Engl J Med 20143702219-2227
A 42 yo man with schizophrenia presents to the ED after being found yelling at cars in traffic On
interview the patient has AVH paranoia and persecutorial delusions Initial toxicology
screening shows only cannabis in urine Patientrsquos only medication is Risperidone Consta 50mg IM q2weeks You call the patientrsquos case manager to
get a sense of baseline Case manager states that current symptoms are clearly worse than usual Chose the correct statement regarding
the case above
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Increases over Time in the Potency of Tetrahydrocannabinol (THC) in Marijuana and the Number of Emergency Department Visits Involving Marijuana Cocaine or Heroin
Volkow ND et al N Engl J Med 20143702219-2227
Use of Marijuana in Relation to Perceived Risk and Daily Use of Tobacco Cigarettes or Marijuana among US Students in Grade 12 1975ndash2013
Volkow ND et al N Engl J Med 20143702219-2227
Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana
Volkow ND et al N Engl J Med 20143702219-2227
Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being
Volkow ND et al N Engl J Med 20143702219-2227
A 42 yo man with schizophrenia presents to the ED after being found yelling at cars in traffic On
interview the patient has AVH paranoia and persecutorial delusions Initial toxicology
screening shows only cannabis in urine Patientrsquos only medication is Risperidone Consta 50mg IM q2weeks You call the patientrsquos case manager to
get a sense of baseline Case manager states that current symptoms are clearly worse than usual Chose the correct statement regarding
the case above
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Use of Marijuana in Relation to Perceived Risk and Daily Use of Tobacco Cigarettes or Marijuana among US Students in Grade 12 1975ndash2013
Volkow ND et al N Engl J Med 20143702219-2227
Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana
Volkow ND et al N Engl J Med 20143702219-2227
Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being
Volkow ND et al N Engl J Med 20143702219-2227
A 42 yo man with schizophrenia presents to the ED after being found yelling at cars in traffic On
interview the patient has AVH paranoia and persecutorial delusions Initial toxicology
screening shows only cannabis in urine Patientrsquos only medication is Risperidone Consta 50mg IM q2weeks You call the patientrsquos case manager to
get a sense of baseline Case manager states that current symptoms are clearly worse than usual Chose the correct statement regarding
the case above
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana
Volkow ND et al N Engl J Med 20143702219-2227
Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being
Volkow ND et al N Engl J Med 20143702219-2227
A 42 yo man with schizophrenia presents to the ED after being found yelling at cars in traffic On
interview the patient has AVH paranoia and persecutorial delusions Initial toxicology
screening shows only cannabis in urine Patientrsquos only medication is Risperidone Consta 50mg IM q2weeks You call the patientrsquos case manager to
get a sense of baseline Case manager states that current symptoms are clearly worse than usual Chose the correct statement regarding
the case above
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being
Volkow ND et al N Engl J Med 20143702219-2227
A 42 yo man with schizophrenia presents to the ED after being found yelling at cars in traffic On
interview the patient has AVH paranoia and persecutorial delusions Initial toxicology
screening shows only cannabis in urine Patientrsquos only medication is Risperidone Consta 50mg IM q2weeks You call the patientrsquos case manager to
get a sense of baseline Case manager states that current symptoms are clearly worse than usual Chose the correct statement regarding
the case above
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
A 42 yo man with schizophrenia presents to the ED after being found yelling at cars in traffic On
interview the patient has AVH paranoia and persecutorial delusions Initial toxicology
screening shows only cannabis in urine Patientrsquos only medication is Risperidone Consta 50mg IM q2weeks You call the patientrsquos case manager to
get a sense of baseline Case manager states that current symptoms are clearly worse than usual Chose the correct statement regarding
the case above
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
A Cannabis use among patients with schizophrenia is associated with more hospital stays and longer episodes of acute care
B It is unknown what if any effect cannabis has on patients with schizophrenia
C Cannabis makes everyone who smokes it prone to transient psychosis
D Δ-9-tetrahydrohydrocannabinol (THC) is the only cannabinoid in marijuana that is psychoactive and it is likely responsible for the acute psychotic presentation of the patient
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Adolescents and MarijuanaGenetic Links
ndash Swedish males using marijuana 6x more likely to be diagnosed with schizophrenia
ndash Catechol-O-methyltransferase (COMT) -degrades dopamine epinephrine and norepinepherine
bull COMT Val108 Met allele homozygotes more likely to develop schizophrenia with THC exposure
bull Carriers of the ValMet allele more sensitive to psychotic effects of THC
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Questions
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Case
bull You are on your family medicine rotation in Spokane Wa working at an outpatient clinic A 24 yo man with history of PTSD his first appointment in this clinic after moving from Alasak for work Your attending says ldquoGo in and get a history then come back and present ndash wersquoll see her together after thatrdquo
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
The patient appears to be in distress saying ldquoI really need help Irsquove run out of my xanax and I need a refill right away My anxiety is out of control and I am not sleepingrdquo As the history unfolds the patient says that he was seeing a psychiatrist previously in Alaska but lost his prescription for xanax during his move He has been out three days and has gone to multiple EDs to attempt getting refills with no avail ldquoAll they do is give me a dose of clonazepam and offer me detox Irsquom not an addict I have PTSD and my doctor prescribes me the medicinerdquo
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
As you attempt to get more history about his use one question you ask is ldquodid you call your doctor in Alaska to ask about a refillrdquo The patient gets upset and says ldquoSo you probably think Irsquom an addict too I tried that and he is out of townrdquo The patient begins to cry and says ldquoare you going to help me or notrdquo His vitals are BP 16085 HR 105 RR 18 Temp 374 You say ldquoIrsquod really like to help you but there are just a few more questions Irsquod like to ask
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
bull What do you want to know
bull What is your attending going to want to know
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
bull Xanax 15 mg TID no other medications or medical problems known
bull Has never run out of meds in the past no history of addiction to other substances no family history of addiction
bull Employed as an asphalt paver has been employed for 5 years consistently
bull PTSD stems from assault he suffered after being beaten severely outside a bar 15 years ago
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Diagnosis
bull You present the information to your attending He says ldquoGreat another straightforward caserdquo
bull What is this patientrsquos diagnosis Do we have enough information to make one
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Physiologic DependenceTolerancebull Patient is in benzodiazepine withdrawal
bull Patient is physiologically dependent on benzodiazepines and has developed tolerance to the medications
bull He does NOT meet criteria for a benzodiazepine use disorder benzodiazepine abuse benzodiazepine dependence in the ldquoaddictionrdquo sense of the termhellipAS OF YET
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Substance use disorderAddictionbull Pathological use of a substance which results in repeated
adverse social consequences related to the drug use ndash Failure to meet work school family obligationsndash Interpersonal conflicts
bull Patients with severe substance use disorders often have features of physiologic dependence and tolerance
bull Having dependence and tolerance does NOT in itself equal substance use disorder ndash see subspecifier in handout
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Opioids
bull What are the signs and symptoms of opiate overdose
bull What are the signs and symptoms of opiate withdrawal
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Medications forOpioid Use Disorder
bull Antagonistndash Naltrexone
bull Agonistsndash Methadone
bull Partial Agonistndash Buprenorphine
Naltrexone forOpioid Use Disorder
bull Most ideal pharmacologic treatment
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Naltrexone forOpioid Use Disorder
bull Most ideal pharmacologic treatment
bull Requires detoxification before initiation or severe withdrawal will be precipitated
bull Requires Naloxone challenge test
bull Risk of OD if medication stopped
bull In general poor patient compliance ( Better with long-acting injection) but superb treatment for selected patients
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Injectable Extended Release Naltrexone for Opioid Dependence
Krupitsky et al 2011
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Methadone Pharmacokineticsand Dosing
bull Rapidly absorbed
bull Peak Levels in 4 hours
bull t12=24 hours
bull Metabolized in liver (p450 3A4)
bull Doses should be individualized but higher doses generally more effective (asymp80-120mg)
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Swedish Methadone StudyBefore
Experimental Group(Methadone)
Control Group(No Methadone)
Gunne amp Gronbladh 1981
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Swedish Methadone Study After 2 YearsExperimental Group
(Methadone)Control Group(No Methadone)
Gunne amp Gronbladh 1981
d
a b
c
d d
a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Methadone Side Effects
bull Minimal sedation once tolerance achievedbull Constipationbull Increased AppetiteWeight Gainbull Lowered Libido May decrease gonadal
hormone levelsbull Prolonged Qtc (screen pts wcardiac disease)bull Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Buprenorphine Pharmacology
Poor oral bioavailability given sublingually (subcutaneous implants experimental patch for pain)
Slow onset (Peak effects 3-6 hrs)
Long duration (24 - 48 hours)
Slow offset
Half life gt 24 hours
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Properties of Buprenorphinea micro-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for micro-opioid receptor
Slowly dissociates from micro-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in temporal proximity to full agonist opioids
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Efficacy
Log Dose of Opioid
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Efficacy Full (Agonist Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone)
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Buprenorphine vs Placebo for Heroin DependenceKakko Lancet 2003
Treatment duration (days)
Rem
aini
ng in
tre
atm
ent
(nr
)
0
5
10
15
20
0 50 100 150 200 250 300 350
Detoxification
Maintenance
4 Subjects in Control Group Died
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Question
In terms of mortality what is the highest risk clinical situation related to opioid use below
A A patient titrated to 90mg of methadone in a methadone clinic
B A patient using 12gram of heroin on a daily basis for 5 years
C A patient who relapses onto heroin after 30 day detoxinpatient treatment episode
D A patient stabilized on 24 mg of daily suboxone who uses heroin on top of the suboxone
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Take Home
bull Life threatening aspect of opioid overdose is respiratory depression ndash stabilize airway and give naloxone (consider t12)
bull Methadone and buprenorphine replacement have been shown to decrease morbidity and mortality while engaging patients in treatment and improving patient outcomes
bull IM naltrexone potentially good option for some patients
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Questions
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Name the Drug
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
What is the primary neurotransmitter involved in cocaine intoxication and
how is it influencedbull A Glutamate cocaine primarily binds to glutamate
receptors blocking stimulation bull B GABA cocaine primarily binds to GABA receptors
blocking stimulationbull C Dopamine cocaine primarily blocks the
transporter responsible for reuptake of dopamine making it over stimulate the cell
bull D Dopamine cocaine stimulates the release of dopamine and blocks the transporter responsible for reuptake making it over stimulate the cell
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Overdose
bull Life threatening conditionndash Vasoconstriction can result in MI and Strokendash Cardiac Arrhythmias and seizures also common
conditions seen on boards
bull Treatmentndash Ensure Cardiac stabilization Supportive Care
symptomatic treatment
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Cocaine + ldquordquobull Levamisole
ndash Antihelminthic adulterant found in up to 70 of cocaine in the US
ndash Potentiates cocaine and adds bulkndash Severe vasculitis
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Long Term Treatment
bull Disulfiram - possibly to help reduce cravings
bull Contingency management ndash most evidencendash Reward positive behavior
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Review
bull A patient presents to the Emergency Department in severe distress Unfortunately the man speaks no English aside from screaming ldquoHelprdquo Vitals are BP 184114 HR 122 RR 18 Temp 378 On physical exam his pupils are dilated he is sweating profusely and clinching his stomach What is the next step in management
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
bull A Give Buprenorphine because patient is in opioid withdrawal
bull B Give Naloxone patient is intoxicated on opioids and at risk for respiratory depression
bull C Start oxygen and obtain EKG because patient is likely intoxicated on cocaine
bull D Give benzodiazepine because patient is likely intoxicated on cocaine
bull E Give 5mg of Haldol and 2mg of lorazepam because patient is likely intoxicated on cocaine
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Amphetaminesbull Similar intoxication syndrome to cocaine but usually
longerbull No vasoconstrictive effectbull Possible neurotoxicity in chronic use possibly from
glutamate and axonal degenerationbull Can see permanent amphetamine psychosis with
long term use
bull Pathogenesisndash Reverses and blocks transport of DA NE Serotoninndash Stimulates release of DAndash Inh monamine oxidase activity
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Treatment ndash amphetamines
bull Withdrawal can last for gt2 weeks and mimic anxiety and depressive disorders
bull CD treatment including support education skills CAndash Treatment similar as for cocaine but no known
substances to reduce cravings
bull No specific medications have been found helpful in treatment
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
ALCOHOL
bull Responsible for 88000 deaths each yearbull 3rd leading preventable cause of death in the US from behavioral factorsbull 40 of all traffic fatalities are related to its use in 2000
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly minor medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo
Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquo
Patient ldquo5rdquo
ConcernsThoughts
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
57yo M with a history of GERD presents to your office for a PPD You have been seeing him for the past 3 years for mostly small medical issues He has recently been diagnosed with hypertension
He presents requesting a TB test to enter court-ordered alcohol treatment after a recent DUI He assures you this was a one-time thing and that he does not have an alcohol problem
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquoPatient ldquoIt is hard to sayrdquoDoctor ldquoOn average how many days a week do you have an alcoholic drinkrdquo Patient ldquo6 out of 7 days It helps me take the edge offrdquoDoctor ldquoOn a typical drinking day how many drinks do you haverdquoPatient ldquo3rdquo
Thoughts Next Steps
Single Item Alcohol ScreenerldquoHow many times in the past year have you had five (four in women) or more drinks in a dayrdquoScoring and Notes Positive response any answer gt0 or difficulty identifying how often Sensitivity 82 Specificity 79 (2) Easy to remember and quick
AUDIT-C (Alcohol Use Disorders Identification Test-Consumption)1 How often do you have a drink containing alcohola Never b Monthly or less c 2-4 times a month d 2-3 times a week e 4 or more times a month
1 How many standard drinks containing alcohol do you have on a typical daya 1 or 2 b 3 or 4 c 5 or 6 d 7 or 9 e 10 or more
1 How often do you have six or more drinks on one occasiona Never b Less than monthly c Monthly d Weekly e Daily or almost daily
Scoring and Notes Scoring a=0 b=1 c=2 d=3 e=4 (3)
o Positive response indicates unhealthy alcohol use Men gt4 Sensitivity 85 Specificity 89 Women gt3 Sensitivity 73 Specificity 91 (4)
o Scores gt7 suggest alcohol dependence (5)
Doctor ldquoHow many times in the past year have you had 5 or more drinks in one dayrdquo
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Healthy Drinking Limits
Healthy Men lt65 years old le 4 drinks in a day and le 14 drinks in a week All Healthy Women and Healthy Men gt 65 years old le 3 drinks in a day and le 7 drinks in a week Abstinence for selected populations Pregnant Medication interactions Health conditions with
contraindications Under 21yo
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Next Steps
bull Make a diagnosis
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Substance use disorderA problematic pattern of substance use leading to clinically significant impairment or distress as manifested
by at least two of the following occurring within a 12-month period bull Failure to fulfill obligations at work school or homebull Use in dangerous situationsbull Cravingbull Continued use despite social or interpersonal problems due to the substance use (fights with significant
other)bull Tolerancebull Withdrawalbull Using more than intendedbull Persistent desire or unsuccessful efforts to cut down or stop usebull Significant time spent getting using or recovering from substance usebull Decreased social or occupational activities due to substance usebull Continued use despite physical or psychological problems
bull Severity specifierbull 2-3 mildbull 4-5 moderatebull 6+ severe
DSM 5-Substance Use Disorders
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
bull On further discussion the patient admits the followingndash His father was a ldquofunctional alcoholicrdquondash He has never been in treatment beforendash This is his first legal issue around drinkingndash He has called in sick to work because of hangoversndash He has thought about drinking at work but is able to resistndash He has never tried to cut backndash Denies increasing amounts but admits to handling his alcohol
much better then when he was youngerndash His ex-wife told him he drank too much and was ldquotoxicrdquo around
his kids but he feels he is fine The kids primarily live with their mother
ndash Drinking helps with his anxiety and sleep
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stability
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Medical Associations of Alcoholbull CV cardiomyopathy afib HTN dysrhythmia coronary artery spasm MI CAD suden death
bull PrenatalPerinatal fetal alcohol effects and syndromebull Hematologic macrocytic anemia pancytopenia leukopenia thrombocytopenia coagulopathy iron
deficiency folate deficienc spur cell anemia burr cell anemiabull Musculoskeletal rhabdo compartment syndromes gout saturnine gout osteopenia osteonecrosisbull Nutritional vitamin and mineral def (B1 B6 Riboflavin Niacin Vit D Mag Ca Folate Phosphate Zinc)
protein
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Psychiatric Associations of Alcohol
Suicide-a real riskRate increased nearly 10 fold in people with an Alcohol Use disorderHeavier drinking days found to be associated with a higher risk
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in change
>
2014
Blues
29649189
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
P R O C H A S K AS T A G E S O F C H A N G E
(the transtheoretical model)
Precontemplation
Contemplation
Preparation
Action
Maintenance
Termination
no intention to take action within next 6 months
intend to take action within next 6 months
intend to take action within 30 days and have already taken some steps to change
behavior has changed for lt 6 months
behavior has changed gt 6 months
not tempted to relapse and certain they will not return to their old behavior
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawal
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
bull Usually 6-8 hours after the last drink (or reduction in heavy drinking)
bull Peaks in 24-48 hours bull Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset
diaphoresis sleep disturbance increases in blood pressure and heart rate
bull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety mood disturbance and poor sleep
Uncomplicated alcohol withdrawal
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
bull High ciwa score (12) elevated vitals with a still elevated Breathalyzer
bull History of complicated withdrawal (DTrsquos)bull Medical issues (heart arrhythmia)bull Unstable psychiatric issues (suicidal)bull Failure of outpatient treatment (not applicable
here)
When to admit for inpatient detox
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
CIWA Scoring
bull Scoringndash Mild lt9ndash Moderate 10-18ndash Severe lt18
bull Do not score if patient is intoxicated
bull Helpful in assessing risk
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Alcohol withdrawal complications
Withdrawal seizures Tonic clonic24-48 hours after last drinkIf multiplefurther work-up requiredRisk factor ho seizures heavy sustained drinking
Delirium tremens Autonomic dysregulation agitation diaphoresis disorientation hallucinations72-96 hours after last drinkMedical Emergencymortality rate 37 if untreatedRisk factor ho DTs heavy sustained drinking concurrent illness
Alcoholic hallucinosis Characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual
Wernickersquos encephalopathy
Encephalopathy paralysis of eye movements and ataxiaAtrophy of mammalar bodies-highly specificReplace thiamine 1st
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Next Steps
bull Make a diagnosisbull Evaluate medical and psychiatric
stabilitybull Evaluate interest in changebull Evaluate risk of withdrawalbull Consider treatment options
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Alcohol Pharmacotherapy Naltrexone-typically 1st line
Opioid receptor blocker cuts back craving and lsquorewardrsquo of useSide effects Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)Cons will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate-often considered 2nd line if on opioids
Structurally similar to GABA may inhibit glutamatergic systemSide effects Diarrhea nausea vomitingPros Can be used in patients with liver disease Cons TID dosing use caution in renal disease
Disulfiram-great for patients with incredible adherence(methadone Disulfiram cocktail)
Blocks aldehyde dehydrogenase blocks breakdown of alcoholWith alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathyMust watch LFTrsquosAVOID in Pregnancy psychosis severe heart disease
Topiramate-consider in pts on opioids or who cannot tolerate disulfiram
Potentiates GABA inhibits glutamate May reduce cravings Side effects sedation decreased appetite weight loss dizziness tremorCaution in renal disease
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Psychosocial Treatments
Brief Interventions Brief 2-4 semi-structured counseling session emphasizing reductionComponents feedback on risk responsibility advice to change goal settingUseful in risky substance use
Harm Reduction Combines compassion and pragmatism to reduce harms of substances User driven ldquoAn attitude more then a procedurerdquo
Motivational therapy Collaborative evocative and autonomy supportive interviewing technique to build motivation to result in change
Cognitive Behavioral Identifies cognitive behavioral and environmental risk factors for relapse prevention Abstinence based
Mutual help groups AA NA CA-abstinence based peer support Dose dependent response Widely available and free
Inpatient Moderate evidence Not found to be consistently better then other approaches May be better for some people
Outpatient A variety of approaches and intensities such as Intensive Outpatient Programs Typically involves regular counseling and monitoring
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
bull Universal screening is recommendedbull Full medical and psychiatric evaluation is
needed if addictedbull Monitor for alcohol withdrawal complicationsbull Long term follow-up is needed
Summary Alcohol
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Nicotine
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
bull Cancers associated with smokingndash Cause proven
bull Colorectalbull Head and neckbull Liverbull Lower urinary tract including renal pelvis ureter and bladderbull Lungbull Mesotheliomabull Myeloid leukemiabull Nasal cavity and paranasal sinusesbull Pancreasbull Penisbull Stomachbull Uterine cervix
Nicotine
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
bull Live longerbull Reduce CV risk after MI by gt 13 over 5 yearsbull Reduce cancer riskbull Improve lung functionbull Reduce risk of infectionsbull Decreased risk for DMIIbull Reduce risk of hip fracturesbull Decrease reproductive disordersbull Etc
Smoking reduction vs cessationndash Maybe helpful for heavy smokers-controversialndash Smokers often compensate-longer puffs etc
Benefits of Stopping
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Varenicline (Chantix)bull A4B2 nicotinic cholinergic receptor (nAChR) partial agonistbull Mimics the action of nicotine amp prevents withdrawal symptomsbull Side effects GI upset psychiatric changesBupropion (zyban)bull Antidepressant that is also a partial agonist at nAChR and inhibitor of
dopamine reuptakebull Helps reduce withdrawal symptoms bull Tremor anxietyNicotine Replacement (gum lozenge inhaler patch)bull Replaces nicotine without additives of tobacco Often used as a combination
of patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
bull Anxiety restlessness GI upset tremor sleep disturbance
Smoking Cessation
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
bull The Five Arsquos Model for facilitating smoking cessation
bull Ask about tobacco use during each visitbull Advise all patients who smoke to quitbull Assess the patientrsquos willingness to quitbull Assist the patient in their quit attemptbull Arrange for follow up
Helping patients QUIT
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
bull Designed to deliver nicotine without tobacco
Good or Bad
e-Cigarettes
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
bull Not found to be a gateway to smoking tobaccobull Content
ndash Propylene glycol glycerolmostly safendash Impurities and toxicants in liquidnot safe but
safer then tobaccondash Nicotine delivered varies
e-Cigarettes current findings
Long term effects of these additives are unknown
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
bull Adverse effects mouth and throat irritation increase in blood pressurendash More serious exploding cartridge lipoid pneumonia afib in eldery ptndash CV increased heart ratendash Resp increased resistance after 5 min of use but deemed not
clinically significantndash Nicotine poisoning 1 report of a child death after drinking e-liquid
bull Less calls to poison control then for tobacco exposure
bull Effect on smoking behaviorndash Reduces urge to smokendash Preliminary evidence for reduction and cessationndash Method choice in England
e-Cigarettes
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Summary Nicotine
bull Donrsquot forget to address nicotine usebull Cessation is the goalbull Multiple quit attempts likely neededbull There are several products that can be helpful
including patches gum bupropion Varenicline and e-cigarettes
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
QUESTIONS
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
THANKS
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
SummarySupplement to Substance Use Disorders ToleranceA need for markedly increased amounts of the substance to achieve intoxication or desired effect ORA markedly diminished effect with continued use of the same amount of the substance WithdrawalThe characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) ORThe substance or one very similar (for example benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid withdrawal symptoms Wernickersquos encephalopathy The ldquoclassic triadrdquo of ataxia nystagmus and mental confusion is a common boards question however in clinical practice all three symptoms are rarely present Wernickersquos is missed in 80 of cases Newer criteria have been proposed bullTwo of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for most of their adult life dietary deficiencies oculomotor abnormalities cerebellar dysfunction and either altered mental status or mild memory impairment Treatment is thiamine
Clinical ManagementClinical PearlsPatients who have had alcohol withdrawal seizures or DTrsquos are considered to have had ldquocomplicated alcohol withdrawalrdquo When getting the clinical history for a patient in alcohol withdrawal it is very important to find outbull how long the patient has been drinking bull how much theyrsquove been drinking bull when their last drink was and bull what their prior symptoms have been when in alcohol withdrawal This helps you stratify their risk during detox make decisions regarding management (Outpatient detox Do they need to be hospitalized) and have a timeline for potential complications of withdrawal Relapse prevention medications following acute medical stabilizationdetoxndash see attached chart 1
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Clinical ManagementUncomplicated alcohol withdrawal bull Begins earlier than the Andreasen textbook suggests usually 6-8 hours after the last drink (or reduction in heavy drinking)bull Peaks in 24-48 hours Subsides within 5-7 days bull Common symptoms anxiety tremor GI upset diaphoresis sleep disturbance increases in blood pressure and heart ratebull There is a lsquoprotracted withdrawal syndromersquo that can continue several months after acute detox is complete this includes anxiety
mood disturbance and poor sleep Alcohol withdrawal seizuresbull Usually occur when patients have had heavy sustained alcohol intakebull Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)bull Tonic-clonicbull Usually one seizure but can be multiple Alcoholic hallucinosisbull As the book notes this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile auditory or visual bull Usually within 48 hours of alcohol cessationbull CLEAR SENSORIUM (if there is altered mental statusmdashconsider DTs)bull Usually resolve within a week but in some cases can be chronic Alcohol - Delirium Tremensbull altered mental status and autonomic dysregulation in the context of alcohol withdrawalbull Rare complication of alcohol withdrawal-5 of hospitalized patients bull MEDICAL EMERGENCY mortality rate if untreated is as high as 25bull Usually emerges 48-96 hours after the last drink patients (and sometimes physicians) can be very confused about what DTrsquos truly are Many patients will tell you they lsquohad the DTrsquosrsquo but will often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal It is important to clarify Were they admitted to the ICU Did a doctor tell them they became very confused or agitated Were they admitted to a hospital and not remember their withdrawal
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Drug-Related DisordersGenetic factors are estimated to contribute to 40-60 of the variability in the risk for addictionReward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens mediated largely by dopamine Underlying mental illness is associated with higher rates of drug use disorder Diagnosis and treatment of these disorders (bipolar psychosis depression anxiety etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board Table 97 Black Signs of intoxicationndash high yield for boards ndash pay particular attention to Eyes Vital signs and Gastrointestinal signs Will be tested Sedatives Hypnotics and Anxiolytics (barbiturates benzodiazepines Alcohol) Clinical Pearlsbull Are all cross-tolerant with one another bull All can cause physical dependence bull Both intoxication and withdrawal are potentially life threatening Neurotransmitter action potentiates effects of Gamma-aminobutyric acid (GABA) inhibitory neurotransmitter by increasing frequency of chloride channel opening
Delirium Tremens ndash disorientation confusion hallucinations (visual and tactile) nystagmus Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)Shorter acting substances are associated with more intense withdrawal symptomsBenzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures DTs)Treatment of sedativealcohol withdrawal (see Black pg 258 key points)bull Patients with history of complicated withdrawal (DTrsquos seizures) should be monitored closely and treated with benzodiazepines to avoid
complications Benzodiazepine overdose (respiratory depression) stabilize airway supportive care On boards ndash give flumazenil Drug not used much clinically ndash can precipitate seizures
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Opioid Use Disorders heroin morphine hydrocodone oxycodone tramadol meperidine Clinical Pearlsbull High mortality rates associated with overdose (respiratory depression) accidental deaths suicide and infections (abscess sepsis
hepatitis C HIV)bull Treatment of acute overdose IV naloxone stabilize airway Neurotransmitters endogenous opiate receptors (mu kappa and delta) Secondary effects on dopamine Withdrawal symptoms (miserable but not life threatening) bull Emerge based on half-life of opiate used If physiologically dependent heroin withdrawal begins 6-12hrs after last use peaking 1-3 days bull Dilated pupils sweating yawning tachycardia hypertension rhinorrhea piloerection hotcold flashes musclejoint pain nausea
vomiting GI crampsdiarrhea Clinical management of acute withdrawal bull Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)bull Symptom management Clonidine for autonomic dysfunction NSAIDs for muscle cramps dicyclomine for GI symptoms bull Replace opiate initiate opiate and taper - methadone suboxone Long-term medical treatment of opiate dependenceMethadone maintenance (only approved in DEA approved methadone programs) Methadone is a full opiate agonist with long half life 24-36 hours on average
Decreases cravings for opiatesBetter results than opiate detoxification aloneEngages patients in treatmentImproves social and occupational functioningDecreases substance use across boardDecreases criminal activity and depressive symptoms
Buprenorphine partial opiate agonist (ceiling effect reduces chances for overdose)Higher binding affinity to opiate receptors than other opiatesSuboxone buprenorphine plus naloxone ndash oral dissolvable tab Naloxone not orally bioavailable so no precipitated withdrawal However if injected naloxone can then precipitate withdrawal Compound prevents misuse of substance Because buprenorphine is a partial opiate agonist with high binding affinity it can precipitate withdrawal in a patient with full opiate agonist on board Must wait to administer until patient in partial opiate withdrawal
Naltrexone full opioid receptor antagonist
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Stimulant use disorders Cocaine Methamphetamine methylphenidate dextroamphetaminePsychological euphoria mediated largely by dopamine cocaine prevents the reuptake of dopaminemethamphetamine stimulates the release and prevents the reuptake of dopamine Intoxication ndash euphoria dilated pupils agitation anxiety possible psychosis vitals signs vary- Treatment of intoxication ndash supportive careOverdose (can be life threatening) ndash acute myocardial infarction andor anoxic brain injury (stroke) secondary to vasoconstriction arrhythmias hyperthermia - Treat secondary disorder MI Stroke hyperthermia Withdrawal ldquocrashrdquo (not life threatening)- extreme fatigue depression intense dysphoria Treatment with supportive care Treatment of dependence contingency management cognitive behavioral therapy can try disulfiram for cravings or relapse prevention but pharmacotherapy options are limited Hallucinogen use disorders peyote mescaline LSD MDMA (Ecstasy) Multiple neurotransmitters dopamine serotonin acetylcholine GABAMDMA (ecstasy) ndash both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndromeIntoxication autonomic hyperarousal perceptual alterations (heightened sensations increase intensity of emotions) Tx Supportive care for intoxicationOverdose tachycardia arrhythmias stroke dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Phencyclidine (PCP) use disorders Neurotransmitters Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neuronsIntoxication out of control behavior violence ataxia hypertension tachycardia hallucinations and depersonalization (Rotatry nystagmus pathognomonic for PCP intoxication - high yield boards)Benzos and antipsychotics for severe agitation or psychotic symptoms Cannabis use disorders Many cannabinoids delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid Secondary effects on dopamineIntoxication (not life threatening) time slowing uarr appetite tachycardia dry mouth paranoia and potential psychotic symptoms Treat with supportive careChronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthoodWithdrawal (not life threatening) insomnia anxiety and nausea Inhalants (toluene acetone benzene found in glue paint gas aerosol cans)Intoxication 5-45 minutes though CNS depressants they can cause euphoria disinhibition excitationAt higher levels can cause respiratory depression slurred speech ataxia delirium Treatment stabilize airway supportive care High Yield Boards - can cause heavy metal poisoning kidney liver and neuromuscular damage
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Nicotine (cigarettes chew and snuff) Up to 25 of adult Americans use regularly More common in people with mental illness (up to 90 in patients with schizophrenia) Leading cause of preventable morbidity and mortality in US Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systemHighly addictive via the dopamine system Withdrawal begins hours after last cigarette peaks in first 24 hours can continue for weeks cravings for months Symptoms include dysphoria anxiety weight gain
Prescribing Practices Medications physicians prescribe such as opiates benzodiazepines and stimulants are drugs of potential abuse and misuse Physicians should consider this risk with all prescriptions given See table 9-8 ndash rationale can be applied to all addictive substances Additional tool Washington Prescription Monitoring Program tracks prescriptions for all controlled substances in the state httpwwwdohwagovForPublicHealthandHealthcareProvidersHealthcareProfessionsandFacilitiesPrescriptionMonitoringProgramPMPaspx
Mimics the action of nicotine amp prevents withdrawal symptoms
GI upset psychiatric changes
Bupropion (zyban) Antidepressant that is also a partial agonist at nAChR and inhibitor of dopamine reuptake
Helps reduce withdrawal symptoms
Tremor anxiety
Nicotine Replacement (gum lozenge inhaler patch)
Same as nicotine Replaces nicotine without additives of tobacco Works best with patch (long acting lsquobasalrsquo nicotine level) and gum or lozenge for break through cravings
Anxiety restlessness GI upset tremor sleep disturbance
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
Nicotine
Benefits of Stopping
Smoking Cessation
Helping patients QUIT
Slide 89
Slide 90
Slide 91
Summary Nicotine
Questions (3)
Thanks
SummarySupplement to Substance Use Disorders
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Slide 101
Slide 102
Chart 1AUD meds
Mechanism of action Side effects Consider avoid
Disulfiram Blocks aldehyde dehydrogenase blocking breakdown of alcohol
With alcohol flushing headache nauseavomiting palpitations shortness of breathWithout alcohol liver failure metallic taste neuropathy
Highly motivated patients those who can be monitored Patients on methadone or other opioids Must watch LFTrsquos
Pregnancy psychosis severe heart disease
Naltrexone Opioid receptor blocker cuts back craving and lsquorewardrsquo of use
Nausea vomiting decreased appetite dizziness Injection site (if using depot formulation)
May work better for patients with a family history of alcohol use disorder Also has a long acting injectable formulation
Opioids wonrsquot work will precipitate withdrawal in those with physiologic dependence on opioids
Acamprosate Structurally similar to GABA may inhibit glutamatergic system
Diarrhea nausea vomiting
Can be used in patients with liver disease TID dosing can make med adherence challenging
Caution in renal disease
Topiramate Anticonvulsant potentiates GABA inhibits glutamate May reduce cravings for alcohol
Sedation decreased appetite weight loss dizziness tremor
Consider in patients on opioids or who cannot tolerate disulfiram
Caution in renal disease Can interact with multiple medications (metformin carbamazepine valproate oral contraceptives)
Substances of Abuse
Goals for today
Addiction ndash As a Brain Disorder
Slide 4
Addiction as a Complex Biopsychosocial Disorder
Addiction as a Chronic Disease
Approach
DSM 5-Substance Use Disorders
Cannabis
Mechanism of Action
Slide 11
Totally safe
Slide 13
Slide 14
Slide 15
Slide 16
A 42 yo man with schizophrenia presents to the ED after being
Slide 18
Adolescents and Marijuana Genetic Links
Slide 20
Questions
Case
The patient appears to be in distress saying ldquoI really need h
Slide 24
Slide 25
Slide 26
Diagnosis
Physiologic DependenceTolerance
Substance use disorderAddiction
Opioids
Opioid Overdose
Slide 32
Medications for Opioid Use Disorder
Naltrexone for Opioid Use Disorder
Slide 35
Slide 36
Methadone Pharmacokinetics and Dosing
Swedish Methadone Study Before
Swedish Methadone Study After 2 Years
Methadone Side Effects
Buprenorphine Pharmacology
Properties of Buprenorphine a micro-Opioid Partial Agonist
Slide 43
Buprenorphine vs Placebo for Heroin Dependence Kakko Lancet 2
Question
Take Home
Questions (2)
Slide 48
What is the primary neurotransmitter involved in cocaine intoxi
Stimulants ndash Cocaine and Methamphetamine
Dopamine Reward
Symptoms
Overdose
Cocaine + ldquordquo
Long Term Treatment
Review
Slide 57
Amphetamines
Treatment ndash amphetamines
Alcohol
Slide 61
Slide 62
Slide 63
Slide 64
Next Steps
DSM 5-Substance Use Disorders (2)
Slide 67
Next Steps (2)
Medical Associations of Alcohol
Psychiatric Associations of Alcohol
Next Steps (3)
Slide 72
Next Steps (4)
Uncomplicated alcohol withdrawal
When to admit for inpatient detox
CIWA Scoring
Alcohol withdrawal complications
Next Steps (5)
Alcohol Pharmacotherapy
Psychosocial Treatments
Summary Alcohol
Nicotine
Slide 83
Leading Preventable Cause of Premature Death in the US
