Prescription Drug Abuse and Addiction, SPF-RX• Vicodin $1/mg • Vyvance $8/40mg • Klonopin $2/2mg • Methadone $5/10mg • Ativan $30/mg • Xanax $4/mg • Ritalin $25/20mg

Raj Masih, MD, MPHRegional Coordinator

WV Strategic Prevent ion Framework for Prescr ipt ion Drugs

WV Region 2

PRESCRIPTION DRUG ABUSE & ADDICTION:

SPF-RX

No financial conflict of interest

DISCLOSURE

23 million Americans have Substance Use Disorder (CDC, 2016)

SCOPE OF THE PROBLEM

There is a massive black market for diverted prescription drugs:

$72 BILLION( D E A , 2 0 1 6 )

FINANCIAL CONSIDERATIONS

Ford Motor Company

Annual sales in 2013:

$11.8 BILLION


Purdue Pharma

Annual sales of OxyContin in 2013:

$10.3 BILLION

( p u r d u e p h a r m a . o r g 2 0 1 4 )


Endo Pharmaceuticals

Annual sales of Endocet in 2013:

$1.6 BILLION

( e n d o . o r g 2 0 1 4 )


Street values:


• Oxycodone $1/mg• Hydrocodone $5/mg• Oxycontin $90/80mg• Opana $50/40mg• Dilaudid 4mg $4/20mg• Adderall 10mg $1.69• Adderall 30mg $5• Percocet $9/10mg• Tramadol $5/100mg• Vicodin $1/mg

• Vyvance $8/40mg• Klonopin $2/2mg• Methadone $5/10mg• Ativan $30/mg• Xanax $4/mg• Ritalin $25/20mg• Codeine Syrup $200/pint• Demerol $10/dose• Fentanyl $100/patch• Morphine $60/100mg• Suboxone $25/strip

(streetrx 2017, justice.gov 2017)

DEFINITIONS

Neonate: an infant less than four weeks old

Addiction: a chronic brain disease characterized by inability to consistently abstain, craving, impairment in behavioral control, and diminished recognition of significant problems related to substance use disorder (ASAM).

Dependence: an adaptive state that develops from repeated drug administration, and which results in withdrawal upon cessation of drug use

DEFINITIONS

WHICH DRUGS ARE ABUSED?

Opioids Heroin OxyContin Oxycodone Oxymorphone Hydrocodone Hydromorphone Morphine Fentanyl Methadone Suboxone Codeine

CNS Stimulants

Amphetamines

Methamphetamines

Cocaine

Crack

Ritalin

SPECIFIC DRUGS OF ABUSE

CNS Depressants

Alcohol

Marijuana

Benzodiazepines

Barbiturates

Sedative - Hypnotics

Methaqualone

Chloral Hydrate


Hallucinogens

LSD

Ecstasy

MDA

MMDA

Inhalants

Nitrous Oxide

Paint

Glue

Paint thinner


EPIDEMIOLOGY

160 deaths per day in the United States from opioids (USDOJ, 2017)

WV has the highest drug overdose death rate: 51.1/100000 people (CDC, 2016)

WV has the highest rate of Neonatal Abstinence Syndrome (NAS) 44.3/1000 live births (CDC, 2016)


In 2016 54,000 Americans died from opioid overdoses (CDC, 2017).

BACKGROUND

30,000 people in WV are in Substance Use Disorder treatment (CDC, 2017)


2007-2013

WV HEALTHCARE AUTHORITY UNIFORM BILLING DATA

119,605 newborn admissions

1974 NAS diagnoses


2007 NAS Incidence Rate

7.74 per 1000 live births

2013 NAS Incidence Rate



In 2013 the southeastern part of West Virginia had the highest incidence rate of NAS:



Reported

Unreported

UNREPORTED NAS BIRTHS PROBLEM IS UNDEFINED AND ALARMING

WHY DRUG ABUSE?

GENERAL MECHANISM OF REWARD

Activation of specific neural pathways that originate in the pons and midbrain and project to the pleasure center in the forebrain

VentralTegmental

Area

Nucleus AccumbensVentral PallidumMedial Pre-frontal CortexAmygdala

ANALGESIC MECHANISMS

Dopamine is in neurotransmitter in the central nervous system and an adrenergic agonist in the peripheral nervous system (Blum, 2011).

WHAT IS DOPAMINE?

Dopamine produces psychotropic effects including mood elevation, euphoria, satisfaction and empathy in physiologic doses (Blum, 2011).

WHAT IS DOPAMINE?

Dopamine is synthesized from the amino acids L-tyrosine and phenylalanine by the enzyme amino acid decarboxylase (AADC), in the presence of pyridoxal 5-phosphate, ionic zinc and magnesium (Blum, 2011).

WHAT IS DOPAMINE?

Adequate levels of bioavailable substrate (L-tyrosine) and phenylalanine are needed to synthesize dopamine in the central nervous system.

WHAT IS DOPAMINE?

Director of NIDA

DR. NORAVOLKOW

The decreased metabolism of dopamine in the D2 receptors of the nucleus accumbens and the amygdala results in a decreased dopaminergic reward in response to normal pleasurable stimuli (Volkow, 2007). This condition is known as dopamine deficiency syndrome or reward deficiency syndrome.

BACKGROUND

Individuals with DDS have been shown to have reduced dopamine release (in the physiological “pleasure centers” of the brain

DOPAMINE DEFICIENCY SYNDROME IN ADDICTIONS

Children with DDS may exhibit maladaptive behaviors such as overeating, binge-eating, consuming and craving large quantities of sugary foods and sugary beverages (Volkow, 2007)


Later in life if these susceptible individuals with the genotypes for DDS are exposed to alcohol or other drugs such as marijuana, opioids, cocaine, or methamphetamine, the neuroplastic and neuro-adaptive changes in the mesolimbic system and pre-frontal cortex become attenuated leading to a pattern of craving and recurrent misuse.


GENERAL MECHANISM OF REWARD

Drugs of abuse such as heroin, opioids, and cocaine increase the release of dopamine at the nucleus accumbens which has a rewarding/reinforcing effect on upper centers in the brain

Chronic opiate use induces neuroadaptations (brain expects it)

RELAPSE

PET SCAN IMAGING

DETERMINING AN ACE SCORE

While you were growing up, during your f irst 18 years of life:

1. Did a parent or other adult in the household often or very often, swear at you, insult you, put you down, or humiliate you or act in a way that made you afraid that you might be physically hurt?If yes enter 1___

2. Did a parent or other adult in the household often or very often, push, grab, slap, or throw something at you or ever hit you so hard that you had marks or were injured? If yes, enter 1___



3. Did an adult person at least 5 years older than you ever touch or fondle you or have you touch their body in a sexual way, attempt or actually have oral, anal, or vaginal intercourse with you?If yes enter 1 ___

4. Did you often or very often feel that no one in your family loved you or thought you were important or special, or your family didn’t look out for each other, feel close to each other, or support each other? If yes enter 1 ___



5. Did you often or very often feel that you didn’t have enough to eat, had to wear dirty clothes, and had no one to protect you, or your parents were too drunk or high to take care of you or take you to the doctor if you needed it? If yes enter 1 ___

6. Were your parents ever separated or divorced? If yes enter 1 ___



7. Was your mother or stepmother often or very often pushed, grabbed, slapped, or had something thrown at her, or sometimes, often, or very often kicked, bitten, hit with a fist, or hit with something hard, or ever repeatedly hit at least a few minutes or threatened with a gun or knife? If yes enter 1 ___

8. Did you live with anyone who was a problem drinker or alcoholic or who used street drugs? If yes enter 1 ___



9. Was a household member depressed or mentally ill , or did a household member attempt suicide? If yes enter 1 ___

10. Did a household member go to prison? If yes enter 1 ___

Now add up your “Yes” answers: ___ This is your ACE Score.

WHAT IS AN ADVERSE CHILDHOOD

EXPERIENCE / ACE?

Growing up experiencing any of the following conditions in the household prior to age 18: 1. Recurrent physical abuse

2. Recurrent emotional abuse

3. Contact sexual abuse

4. An alcohol and/or drug abuser in the household

5. An incarcerated household member

6. Family member who is chronically depressed, mentally ill, institutionalized, or suicidal

7. Mother is treated violently

8. One or no parents

9. Physical neglect

10. Emotional neglect

RELAPSE

Changes in reward circuitry can become permanent, leading to an inability to experience pleasure through any event

This is the set up for relapse

Coupling of reward circuitry with visual cortex and memory pathways can cause craving by simply viewing images of drugs

GENETICS OF ADDICTION

OPRM-1 gene Codes for opioid addiction

1189 variant codes for alcoholism

OPRD-1 gene Codes for heroin addiction

Brain imaging studies have confirmed that individuals with OPRD-1 and OPRM-1 genotypes are predisposed to not only dopamine deficiency in the limbic system and nucleus accumbens of the brain, but are also susceptible to opioid and alcohol addiction (Volkow, 2007).


DNA swab that determines genetic susceptibility to addiction High

Intermediate

Low

PROOVE TEST

CRAVINGS“I HAVE TO TAKE A LEAK”

-DR. NORA VOLKOW

NEUROPHYSIOLOGY OF CRAVING

Release of dopamine in the ventral tegmental area (VTA), and the nucleus accumbens (NA) leads to profound euphoria

Animal studies show stimulation of the dopamine system, by a lever press, leads to ignoring water, food and rest

The dopamine system stimulation leads to changes in reward circuitry

PATHOPHYSIOLOGY

Diagnosis

Heritability

Etiology

Course

Pathophysiology

CHARACTERISTICS OF CHRONIC DISEASES

According to the DSM V, addiction must have three or more of seven criteria

Must have tolerance and withdrawal

Compulsive desire, despite serious consequences

DIAGNOSIS

Most treatment strategies view drug addiction as a curable acute condition rather than a chronic disease

Treatment models need to be the same for Type II Diabetes, hypertension and asthma

FALSE TREATMENT MODEL

Twin studies of Hypertension range from 0.25 to 0.50

Twin studies of Diabetes range from 0.30 to 0.55

Twin studies of Asthma range from 0.36 to 0.70

Twin studies of Heroin Addiction range from 0.34 to 0.55

GENETIC HERITABILITY

Less than 60% of patients with Diabetes II adhere to their medication

Less than 30% of patients with Diabetes II adhere to their diet and behavioral changes

Less than 40% of patients with Hypertension and Asthma adhere to their medication

Less than 30% of these patients adhere to their diet and behavioral changes

COMPARISON WITH OTHER CHRONIC DISEASES

Since the use of any drug is voluntary, behavioral control is important

Does the voluntary initiation of the disease process set drug dependence apart from other medical illnesses?

ROLE OF PERSONAL RESPONSIBILITY

Voluntary choice affects initiation of disease, especially when these choices interact with genetic and cultural factors

Salt sensitivity among males

Obesity

Role of inactivity in Hypertension

Role of diet in Diabetes II

PERSONAL RESPONSIBILITY IN OTHER CHRONIC DISEASES

Many substance use disorder treatment models deliver treatment in a manner that is more appropriate for acute care disorders

Many patients receive detox only

Many patients are admitted to specialized treatment programs where the goal is to rehabilitate them much as a surgical patient is rehabilitated following a joint replacement

PARADOX OF ACUTE ILLNESS MODEL

Hypertensive patients would be admitted to a 28 day hypertension rehabilitation program

Patients would receive group and individual counseling regarding behavioral control of diet, exercise, and lifestyle

Very few would be prescribed medications

Discharged patients would follow up with community resources without medical follow-up

APPLYING THIS TREATMENT MODEL TO HYPERTENSION

Evaluation at 6-12 months

Success of the program would be measured by how many patients have normal blood pressure during the entire post-discharge period

APPLYING THIS TREATMENT MODEL TO HYPERTENSION

MEDICATION ASSISTED TREATMENT (MAT)

Methadone

Suboxone

Subutex

Naltrexone

Probuphine

WHAT DRUGS ARE USED IN MAT?

Changes in reward circuitry can become permanent, leading to an inability to experience pleasure through any event

This is the set up for relapse

Coupling of reward circuitry with visual cortex and memory pathways can cause craving by simply viewing images of drugs

WHY MAT MAKES SENSE

Documents

Prescription Drug Abuse and Addiction, SPF-RX• Vicodin $1/mg • Vyvance $8/40mg • Klonopin $2/2mg • Methadone $5/10mg • Ativan $30/mg • Xanax $4/mg • Ritalin $25/20mg