Hyperdynamic Drugs

ACCESS – CE – 2016 07 Hyperdynamic Drugscc: Leo Reynolds - https://www.flickr.com/photos/49968232@N00

Objectives

• Discuss the Hyperdynamic/Sympathomemetic toxidrome

• Describe and differentiate the following Hyperdynamic Drugs

• Amphetamines • Methamphetamines, Amphetamines, MDMA

• Synthetic Cathinone's

• Cocaine Derivatives

• Discuss pitfalls in the treatment of hyperdynamic crisis

• Lethal H’s

• Haldol

• Restraint

• Agitated / Excited Delirium

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PATHOPHYSIOLOGY

Stimulants or Hyperdymanics?

What is a Toxidrome?

• syn·drome (ˈsinˌdrōm/)

• noun• 1. a group of symptoms that

consistently occur together or a condition characterized by a set of associated symptoms.

• tox·i·drome (ˈtäksiˌdrōm/)

• noun• 1. a group of signs and

symptoms constituting the basis for a diagnosis of poisoning.

In other words: A toxidrome is a “syndrome” that specifically relates to a specific toxinBe cautious, many syndromes/toxidromes are subtle and overlap their symptoms. Thorough assessment is essential

What are the:

Similarities? Most cause….• Pupils (dilated)• Decreased Sleep/Insomia• Increased Heart Rate• Increased B/P• Increased Body Temp• Increased CO2 production ( ↑

ETCO2)– Decreased pH over Time

• Increased O2 consumption(may or may not affect SPO2)

Differences?• Route• Onset• Mental Status

– Hallucinations– Mania– Agitation– Paranoia– Somnolence?

• Cardio Toxic vs. Simply Cardio stressful?

• Neuro-toxic? – Seizures?

• Primary and secondary causes of Mortality

Remember…

• Other problems can cause stimulant like behavior…

• Drug withdrawal

• Psychosis/Behavioral Conditions

• Delirium

• Other Toxins– Dissascoiatives (i.e. PCP)

– Drug side effects

• Other Medical Conditions

Sympathomimetic Toxidrome

• Drug Specific• Mydriasis

– Dilation of Pupil

• Tachycardia• Cardiac Stress

– Chest Pain, SOB, etc– CHF

• HTN– Increased risk of stroke– Aneurysms– Head Ache– Cerebral Bleeds

• Abd Pain– Mesenteric Ischemia

• Diaphoresis– May not occur in severe

hyperthermia and dehydration

• Acute psychosis– Paranoia– Combative– SOB– Anxiety

• Delirium• Bruxism

The Lethal H’s

Hypoxia

Hypercarbia

H+ (Acidosis)

Hyperthermia

Additional Complications• Route/Use Specific

• IV use-• Rapid Onset

• Increased intensity

• Increased mortality

• Smoking-• Rapid Onset

• Wheezing

• Intra-nasal• Rapid Onset

• Mucosal Damage

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Additional Complications

• Multiple Day Use– Increased risk of

hyperthermia and

delirium

– Increased paranoia and agitation

– Increased mortality

• Lack of sleep = Psychosis and Paranoia

Additional Complications

• Restraint related deaths• Do not restrain prone

STREET TIP: NAKED and AGITATED = consider sympathomimetic toxin

Hyperdynamic Drugs in Pregnancy

Don’t forget about the safety of the children….

And yourselves…

TREATMENT

Remember…

• If they are altered in their mental status…

– Stroke Assessment

– Check for head trauma and spontanous head bleeds

– Check BG

– Check Temp

– A.E.I.O.U. T.I.P.S.

The Lethal H’s

Hypoxia

Hypercarbia

H+ (Acidosis)

Hyperthermia

Essential Treatment

“…If removal of noxious stimulus fails to resolve episode,

pharmacologic therapy is indicated.”

- ACP/ACCESS SWO’s M-14

Benzodiazepines

“ Management of agitated or combative patients: Use of sedatives (Benzodiazepines) is highly recommended for even moderate agitation from hyperdynamic use, and may decrease heat production, decrease cardiac toxicity, and improve outcomes, as well as improve provider safety”

-ACP/ACCESS SWO R-3 “Hyperdynamic Crisis/Overdose” dates May 1, 2016

Benzo Doses

• All Benzo’s require SPO2 and EKG – (and should also strongly consider Nasal ETCO2)

• High potentiation with opioids and ETOH– use with caution

• Diazepam– 2.5-5 mg

• Lorazepam– 0.5-2 mg

• Midazolam– 0.5-1 mg

Antipsychotics

Why the caution on Haldol?

Adjunctive Medications

• Adjunctive medications: These medications are given for their potentiation of other drugs effects or for the prevention/treatment of certain side effects (nausea, EPS, etc) of drugs used in sedation.

• Zofran (ondansetron) IV /IM/IO

– Adult: 4 mg

– Pediatric: 0.1 mg/kg to a maximum of 4 mg

The NEW Saturday Night Special ?

• Diazepam

– 2.5-5 mg

• SPO2, EKG, and ETCO2 monitoring

• Temperature

Ketamine

What do our docs say?

• “Benzodiazepines are still first line for the agitation and hyper dynamic crisis. “

• Dr. Ben Cornett 5/2016

• “There is some discussion at a national level of what exactly is best. I don't think we need to rush off and do something because it is trendy without evaluating what is right.”

• Dr. Ian Butler-Hall 06/2016

Ketamine(NOT CURRENTLY IN OUR SWOs)

• NOT CURRENTLY IN OUR SWO”S• Dose is different from RSI!!!

– 0.5-1 mg / kg

• Advantages– Very rapid onset, – Airway Reflexes tend to remain intact– Multiple Routes (IM, IV)– Typically effective in one dose

• Disadvantages– No SZ suppression– Increased monitoring– Must monitor SPO2 and ETCO2 closely

• Misc– DEA Schedule III– Often successful when other drugs fail– Yes it increases HR and B/P, but this was rarely clinically significant– SPO2 decreases have been reported, but this may be due to restraint position rather than the

drug.

Fluids and Cooling

“Obtain patient’s temperature and cool/warm as necessary”

-ACP/ACCESS SWO R-3 “Hyperdynamic Crisis/Overdose” dated

May 1, 2016

“Initiate passive cooling for temperature < 103 F or 39.5 C “ and “Promote cooling; initiate active cooling for significant hyperthermia for temperature > 103 F or 39.5 C “

-ACP/ACCESS SWO R-3 “Adult Heat Emergencies” dated OCT 15,

2014

Restraint

Restraints may be used for patient and/or rescuer safety:• Do not restrain prone. • 4 point restraints are recommended • Observe and prevent positional asphyxia. • Monitor airway and respirations closely. • If restrained, do not release restraints until at the hospital

unless required for essential patient care • Do not leave patient unattended • Allow for adequate heat dissipation

KEY POINT!!!!!

DO NOT RESTRAIN PRONE

Chest Pain and Stimulants

• Chest pain and anginal equilivents (such as SOB, chest pressure, left arm pain) are a common result of stimulant use.

• Some drugs are directly toxic to the heart. Some are merely stressful on the heart, aggravating pre-existing coronary artery disease.

• Nitrates remain indicated for chest pain and Angina equivalents.

• Benzodiazepines are acceptable adjunctive therapies as well in addition to nitrates.

Drug Induced Symptomatic Tachycardia

• Cooling

• Fluid Boluses (If no sign of CHF)

• Benzodiazepines

• Symptomatic tachycardias refractory to Benzodiazepines: – Lidocaine is the anti-arrhythmic of choice for

refractory monomorphic ventricular tachycardia (VT).

– Magnesium Sulfate remains the antiarrhythmic of choice for polymorphic VT (Torsades), although should be used with caution when hypotension is present.

Drug Induced Symptomatic Tachycardia

• Cooling

• Fluid Boluses (If no sign of CHF)

• Benzodiazipines

• Symptomatic tachycardias refractory to Benzodiazepines: Lidocaine is the anti-arrhythmic of choice for refractory monomorphic ventricular tachycardia (VT). Magnesium Sulfate remains the antiarrhythmic of choice for polymorphic VT (Torsades), although should be used with caution when hypotension is present.

REMEMBER: overdoses are AMS calls first, overdoses last

• A - alcohol, alcohol withdrawal, and anoxia• E - epilepsy and other neurological disorders• I - insulin (Hyper or Hypo-glycemia)• O- overdose (Poly-pharmacy?)• U - uremia, underdose of current medications.• T- trauma• I - infection• P - psychiatric• S - stroke, shock states

AMPHETAMINES

This includes….• Amphetamine• METHamphetamine• Prescription Amphetamines• And…• Ecstasy (MDMA)

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How Long has Meth and other Amphetamines been around?

• Jan 18, 1887-Amphetamine was first synthesized by a German chemist

• 1919- Methamphetamine is first synthesized (in Japan)

• WWII -Both Amphetamine and Methamphetamine (by the Japanese mostly)are widely distributed to soldiers to help improve performance. This led to addiction problems in Japan after the war.

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Background- Meth and other Amphetamines

• “Meth" is methamphetamine, which is a type of amphetamine.

• The chemical Methamphetamine is composed of an amphetamine molecule with an additional methyl group attached to its nitrogen (amine group).

• For Methamphetamine, the methyl allows it a little better fat solubility and thus better penetration into the brain.

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MDMA

• Developed in Germany in early 1900’s• Patent in 1913 as potential

• Dormant recreationally until 1970s

• Banned by DEA in 1985 – Schedule I

• Demographic- HS through mid 30’s

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Meth vs. MDMA

• Duration• 6-12 hrs

• Sympathetic Effects• Strong

• Recreational Effects• Energy, Mania• Paranoia

• Risk Profile• Strong for HTN,

Hyperthermia,• toxins from Productions

• Duration• 2-6 hrs

• Sympathetic Effects• Moderate

• Recreational Effects• Energy, Empathy• Hallucinations

• Risk Profile• Strong for Hyperthermia

and Dehydration• Poly-substance

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MDMA…What is does…

• MDMA is best described as an _____________ with _____________ properties.

• Many of the effects are dose dependent.– Auditory and/or visual hallucinations are not commonly

observed.

– Tactile hallucinations and Tactile euphoria more common.

– Much of the abuse potential lies in its pleasurable subjective effects (eg, empathy, euphoria, disinhibition, increased sensuality).• AKA: “The Hug Drug”

AmphetamineHallucinogenic

What Kills…• LETHAL H’s• HYPERTHERMIA

• HYPOXIA

• Hypercarbia

• H+ (Acidosis)

• Restraint related deaths• Do not restrain prone

• No not promote the lethal H’s

• Other Causes

• Dehydration

• Kidney Failure

• Misadventure

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Long term effects

• Methamphetamine is an anorexant, This is considered a benefit

for many light users, but in regular or heavy users can lead to

malnutrition.

• Methamphetamine is also believed to be neurotoxic.It’s use

causes damage to the neurons in the dopamine portions of the

brain.

• Some possible effect on the serotonin producing parts of the

brain is also suspected.

• Lead Poisoning

• Psuedo-Parkinson's D/O

SYNTHETIC CATHINONES(AKA BATH SALTS)

3, 4-Methylenedioxypyrovalerone (MDPV) and other Synthetic Cathinones

(AKA Bath Salts)

(a.k.a. “Bath Salts”)

What are Cathinones?

• Cathinone, a central nervous system stimulant found in the leaves of the “khat” bush (Catha edulis) is also known as African salad, bushman's tea, gat, kat, miraa, qat, chat, tohai, and tschat

• Khat (Catha edulis) is Ethiopia’s fourth biggest export (after coffee, leather & oil seeds) and is growing every year.

• It is a traditional narcotic and is exported mainly to Somalia and Djibouti and then to the U.S. and Europe.

– Degrades rapidly in its natural form

• Causes stimulation, then euphoria and then depression.

What are Synthetic Cathinones?

• Synthetic cathinone's are related to the parent compound cathinone. They are created synthetically (in a lab) resulting in much more potent stimulant effect.

• These products are usually encountered as highly pure white or brown powders.

• Cathinone derivatives are claimed to have effects similar to those of cocaine, amphetamine or MDMA (ecstasy). Some of the Synthetic Cathinones have properties tied to some dissassociatives like PCP and Ketamine. – Like many stimulants increases secretion of dopamine on the brain,

and blocks it reuptake as well, dramatically increasing levels.

Synthetic Cathinones

• Route: Intranasal most common

• Also: oral, smoking, rectal, and IV

• White to light brown crumbly powder

• Degrades if exposed to air for significant periods of time

http://www.stompin-gardeners.com/index.

MDMA

Synthetic Cathinones and MDMA

Types of Bath Salts

2nd / 3rd Generation Cathinones

• Naphyrone (AKA O-2482, NRG-1)) • “Triple Re-uptake Inhibitor” similar to Cocaine

– Dopamine– Norepinephrine– Serotonin

• “Substituted Cathinones”• Result:

– Stronger Stimulation– Longer effects– Higher Mortality

Product Marketing

• Mtv

• MDPK

• Magic

• Super Coke

• Peevee

• Energy-1 (NRG1)

• Charge Plus

• White Lightning

• Scarface

• Cloud 9

• Ocean

• Ivory Wave

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Alcohol and Bath Salts

What makes Synthetic Cathinones different from other sympathomimetics?

• Duration – Shorter, requiring more frequent “bumps”

• Recreational Effects- More intense, less enjoyable

• Clinical Effects – More intense, more clinically significant

– Sympathomimetic toxidrome AND:

• Disassociation

• Impulse/Anger control compromises

• Hallucinations

Duration of effects:

• Note: Duration of effects is highly dose-dependent.

Bath Salts and the Zombie Apocalypse

Nom Nom Nom!

Not Zombies … Yet Bath Salts are deadly

More recent rash of bizarre and deadly bath salts incidents

• - A man was found in the middle of a busy street shouting incoherently at oncoming traffic that swerved to miss him. Police finally got him out of the traffic when he “displayed signs of excited delirium” before he stopped breathing. He was pronounced dead at the hospital and had bath salts on him.

• June 15, 2012. Robinson, Illlinois - A naked man grabs onto random car hood while naked and surfs car hood for 4 miles. The driver calls 911 and drives 4 miles to meet police who then arrested the man, who had vials purportedly containing bath salts on him. He was “hallucinating wildly” … as opposed to hallucinating modestly.

• June 14, 2012. Miami, Florida - A naked woman punched and choked her 3 year old son before the son was rescued by onlookers. She then grabbed her dog and did the same before the police came and tasered. She died from cardiac arrest shortly thereafter

KEY POINT

• Many of these behaviors fit in with classic “Excited Delirium” and are not specific to Synthetic Cathinones

• Use caution when restraining

• Use lots of benzodiazipines, cooling, etc.

COCAINE DERIVATIVES

Everybody loves cocaine

• “…Woe to you my Princess, when I come, I will kiss you quite red and feed you till you are plump. And if you are forward, you shall see who is the stronger, a gentle little girl who doesn't eat enough or a big wild man who has cocaine in his body."-- Sigmund Freud, On Coca

Background- Cocaine

Background

• Sold commercially since 1860’s.

• Cocaine Hydrochloride is available on the

street generally at 30% to 40% purity and

retails at prices ranging from $10.00 to $50.00

per quarter gram.

• Cocaine metabolites are excreted in the urine

and can be detected for between 2 to 4 days

after the drug has been consumed.

Physiological effects

• Sodium Blockade Stimulant effects due to increased Dopamine excretion in the brain (like most hyperdynamics)

• Stimulant effects to due to reuptake inhibition of Dopamine, Serotonin, and Norepinephrine.– Causes central and peripheral effects, including the

release of epinepherine, and hypertension from vasoconstriction

– Increases nor-epi and epi levels 5x!

• Unlike other hyperdynamics, Cocaine also causes sodium blockade similar to TCA’s.

Types of Cocaine

• Cocaine

• Crack

• Low Potency

Main routes of administration

Insufflated Cocaine

• Bioavailability depends on administration

– IN: 60-80% (25-40% nasal spray)

– Rapid onset

– Duration 90-120 minutes

Comments about IV Use

• Rapid Onset with high bioavailability and short duration (60 minutes) due to rapid metabolism– Peak in 3-5 minutes

• Highest incidence of side effects

• “Bell Ringer” – Tinnitus

– Auditory Distortion

• Risk of stroke from circulatory emboli of undissolved particulates

Comment about Crack and Smoking

• Faster onset than IV (surprisingly)

– 1.5 min vs. 3 min

• Acute Pulmonary Effects

– Atrophy of mucosal membrains

– Wheezing

– Impairs Pulmonary Blood flow due to vasoconstriction

– Pneumothorax

– Pulmonary HTN and Edema

• Chronic Pulmonary Effects: “Crack Lung”

Low Potency Cocaine

Cocaine and Alcohol

• Co-imbibing cocaine and alcohol form toxic metabolite cocaethylene– Decreases excretion by 50% = 2-2.5 x longer

duration of effects

• Cocaethylene is also directly cardiotoxic. – Lower LD50 compared to cocaine alone

– Increased stimulation effects

– Decrease in cardiac output by 45-50%

– Increase in ventricular dysrythmias

Cocaine and Alcohol

• “Cocaine and ethanol in combination were more toxic than either substance alone. Co-administration resulted in prolonged cardiac toxicity and was dysrhythmogenic. Peak serum cocaethylene concentrations were associated with prolonged myocardial depression.”

– Wilson, L. D.; Jeromin, J; Garvey, L; Dorbandt, A (2001). "Cocaine, ethanol, and cocaethylene cardiotoxity in an animal model of cocaine

and ethanol abuse". Academic Emergency Medicine 8 (3): 211–22.

Cocaine induced chest pain

• MI rates in cocaine induced chest pain between 15-40%. – High rate of N-STEMI

– MI may occur up to 2 weeks after cocaine use due to recurrent coronary vasospasm.

– All cocaine induced chest pain should be transported to PCI capable facilities

• Like other hyperdynamics, benzodiazepines and NTG are first-line agents in drug-induced acute coronary syndromes.

KEY POINT

• The Sympathetic Toxidrome common to most hyperdynamic drugs may not be present with cocaine induced chest pain due to delayed ischemia and myocardial infarction up to 2 weeks later.

Aspirin?

• Aspirin use in cocaine induced chest pain is poorly studied.

• Aspirin should generally be given to patients with cocaine-associated chest pain.

• It should only be withheld if there is a suspicion of intracranial hemorrhage or aortic dissection.

– Both are real concerns

Pleuratic Pain is misleading

• The character of the pain is not helpful because between 1% and 29% of patients with cocaine-associated myocardial infarction complain of pleuritic pain.

• Relatively young age of patient also misleading.

Cocaine induced dysthymias

• Three (likely causes)

– Adrenergic Stimulation causing ischemia and irritability

– Sodium channel blockade causing conduction problems (similar to TCA’s)

– Chronic cocaine use causes structural abnormalities in conduction pathways leading to re-entry issues.

Cocaine induced dysthymias

• Like all hyperdynamics, Benzodiazepines are first line agents

• Consider Sodium Bicarb for wide complex dysrhythmias (QRS > 100 ms).

• Cocaine induced dysrhythmias will typically notrespond to Adenocard

• Ca+ channel blockers not well studied in this setting.

• Amiodarone and procainamide should be avoided.

• Lidocaine may be considered for refractory wide complex dysrhythmias

Cocaine induced stroke

• Embolic/TIA– Vasoconstriction

– IV cocaine = Risk of stroke from circulatory emboli of undissolved particulates

• Hemorrhagic– powdered cocaine is four times more likely to

cause hemorrhagic strokes than crack

– Cocaine-induced hemorrhagic strokes are generally either subarachnoid (SAH) or intracerebral.

Summery of Treatment

The Lethal H’s

Hypoxia

Hypercarbia

H+ (Acidosis)

Hyperthermia

Beware of In custody Death

• Quiet is bad

• Prone is bad

Questions?