Learning Objectives Based Care...Alice in Toxland: Case‐Based Treatment and Transitions of Care...

Alice in Toxland: Case‐Based Treatment and Transitions of Care for

Hallucinogen, Stimulant, and Depressant Overdoses

Megan Corrigan, PharmD, BCPS

Phillipe Mentler, PharmD, BCPS

Learning Objectives

• Identify hallucinogens and describe treatment for overdose situations

• Summarize the treatment for overdose situations of stimulants

• Explain the treatment for overdose situations for opiates and depressant drugs

Disclaimer

• We have never done illicit drugs

• What is our experience?

• Journal publications and books

• Work in the Emergency Department

• Friends, colleagues, and users

• Internet

Internet Resources• Erowid

• erowid.org

• The users site

• American Association of Poison Control Centers

• aapcc.org

• Poison control center data; useful alerts, statistics, somewhat limited/dated info

• National Institute on Drug Abuse

• nida.nih.gov

• Lay person level info, nice pictures, dated info

• Community Epidemiology Work Group (CEWG): monitors regional trends but 6 month+ delay

Internet Resources

• The Substance Abuse and Mental Health Services Administration

• dawninfo.samhsa.gov

• Drug Abuse Warning Network (DAWN): National/Regional Data based on ED visits but 1 year+ delay

• National Drug Early Warning System (NDEWS)

• http://www.drugabuse.gov

• Initiated July 2014

• Goal to offer “real time” information on emerging trends

The Mad Hatter: Hallucinogens

Megan Corrigan, PharmD, BCPSEmergency Medicine Clinical PharmacistAdvocate Illinois Masonic Medical Center

2014 Midyear Clinical Meeting Alice in Toxland: Case-Based Treatment and Transitions of Care for Hallucinogen, Stimulant, and Depressant Overdoses

© 2014 American Society of Health-System Pharmacists 1

Hallucinogens• Alter and distort perception, thought, and mood• Natural or synthetic• Structural Classes

• Lysergamides• Tryptamines• Amphetamines• Arylhexamines• Cannabinoids• Harmine alkaloids• Belladonna alkaloids• Tropane alkaloids• Miscellaneous

Babu, K. (2010). Goldfrank’s Toxicologic Emergencies, 9th Edition: Hallucinogens. New York: McGraw Hill Medical.

Historical Use• Historically, largely during religious ceremonies

• Naturally occurring hallucinogens

• Synthetic use began in Medieval Ages (5th‐15th Centuries)

• 1938: LSD‐25 was synthesized

• 1950s: Medicinally used in psychiatry

• 1960s: Increased use by the public

• 1966: Banned by the FDA

• 1990s: Resurgence of use

• Current: Often used at raves as well as recreational use from internet sales of “herbal” products

Woolf AT, et al. J Toxicol Clin Toxicol. 2000;38:457‐460. Schwarz RH. Pediartc Emerg Clin North Am. 1995;42:403‐413.Neill JR. J Psychoactive Drugs. 1987;19:39‐45. Bellis MA, et al. Addiction. 2003;98:1713‐1721. O’Malley P, et al. Pediatr Clin North Am. 1995;42:241‐260. Dennehy CE, et al. Ann Pharmacother. 2005;39:1634‐39.

Current Use

• About 1% of Emergency Room visits from illicit drug use are due to hallucinogens

• Excluding cannabinoids and amphetamines

• Poison Center Data

• Over 3,000 calls for hallucinogen drug overdoses

Drug Abuse Warning Network. (2011). Drug Abuse Warning Network, 2011: National Estimates of Drug‐Related Emergency Department Visits. Retrieved from: http://samhsa.gov/data/2k13/DAWN2k11ED/DAWN2k11ED.htm. Mowry JB, et al. Clin Toxicol. 2013:51;949–1229.

CASE• 19 YO male dropped off to the ED after ingestion of “cold medicine” 12 hours ago

• Vitals: RR: 18 HR: 128 BP: 177/113 Temp: 38.5°C • Physical exam

• Pupils dilated• Skin warm to touch, + bowel sounds, patellar and achilles deep tendon reflexes were increased compared to upper extremities

• Bilateral sustained ankle clonus• Hallucinations• Uncooperative

• ECG• Sinus tachycardia, normal PR, QRS, QT, and QTcintervals

What would you order next?

Restrain the patient in hard restraints

Administer a benzodiazepine

Administer an antipsychotic

Do nothing and get a urine drug screen

Lysergic acid diethylamide (LSD)• Synthetic lysergamide: lysergic acid diethylamide (LSD)

• Derived from fungus Claviceps purpurea

• LSD

• Dissolved in mouth

• Other routes available

• Use is primarily abuse for its

hallucinogenic properties

• Most “papers” contain 25‐150 mcg

• Historically, experimented in treatment of alcoholics

• Onset: 30 min

• Duration: 10‐12 hoursSmith DE, et al. J Psychoactive Drugs. 2014;46(1):3‐10.Babu, K. (2010). Goldfrank’s Toxicologic Emergencies, 9th Edition: Hallucinogens. New York: McGraw Hill Medical.



Lysergic acid diethylamide (LSD)

• Mechanism of Action

• Stimulates 5‐HT2 receptors

• Alters activity of serotonin and dopamine in brain

• Presentation

• Anxiety

• Psychosis

• Dilated pupils

• Hyperthermia

Smith DE, et al. J Psychoactive Drugs. 2014;46(1):3‐10.Babu, K. (2010). Goldfrank’s Toxicologic Emergencies, 9th Edition: Hallucinogens. New York: McGraw Hill Medical.

Lysergic acid diethylamide (LSD)• “Bad trip”

• Paranoid• Bizarre behavior• Combative• Tearful• Sympathomimetic side effects

• Life‐threatening• Seizures• Cardiac arrhythmias• Hyperthermia• Hypertension

Smith DE, et al. J Psychoactive Drugs. 2014;46(1):3‐10.Babu, K. (2010). Goldfrank’s Toxicologic Emergencies, 9th Edition: Hallucinogens. New York: McGraw Hill Medical.

Lysergic acid diethylamide (LSD)• Treatment

• Agitation• Diazepam • Midazolam• Haloperidol

• Hyperthermia• Rapid cooling• Treat shivering if occurs

• Hyperthermia• Anti‐hypertensives

• Caution with co‐ingestionSmith DE, et al. J Psychoactive Drugs. 2014;46(1):3‐10.Babu, K. (2010). Goldfrank’s Toxicologic Emergencies, 9th Edition: Hallucinogens. New York: McGraw Hill Medical.

Phencyclidine (PCP) and Ketamine

• Mechanism of Action• Dissociative anesthetic first used in veterinary practice• Loss of pain perception without airway compromise• Stimulate sigma opioid receptors, inhibit gaba reuptake

of dopamine, norepinephrine, and serotonin• Doses

• PCP: 1‐6 mg/tablet• 6‐10 mg causes psychosis• 150‐200 mg can cause death

• Ketamine: 10‐250 mg intranasally, 40‐450 mg orally or rectally, 10‐100 mg intramuscular• “K‐hole” occurs at higher doses

Babu, K. (2010). Goldfrank’s Toxicologic Emergencies, 9th Edition: Hallucinogens. New York: McGraw Hill Medical.Bey T, et al. Calif J Emerg Med. 2007;8(1):9‐14


• Mild Presentation

• Lethargy

• Euphoria

• Hallucinations

• Bizarre behavior

• Hypersalivation

• Vertical and horizontal nystagmus

• Severe Presentation

• Adrenergic hyperactivity

• Hyperthermia

• Self‐destructive behavior

* Chronic ketamine use can cause memory impairment *

Babu, K. (2010). Goldfrank’s Toxicologic Emergencies, 9th Edition: Hallucinogens. New York: McGraw Hill Medical.Bey T, et al. Calif J Emerg Med. 2007;8(1):9‐14Pappachan JM, et al. Proc (Bayl Univ Med Cent). 2014;27(3):223‐225.


• Treatment • Agitation

• Diazepam • Midazolam• Haloperidol• ** No physostigmine **

• Hyperthermia• Rapid cooling• Treat shivering if occurs

• Hyperthermia• Anti‐hypertensives• Caution with co‐ingestion

Babu, K. (2010). Goldfrank’s Toxicologic Emergencies, 9th Edition: Hallucinogens. New York: McGraw Hill Medical.Bey T, et al. Calif J Emerg Med. 2007;8(1):9‐14



Dextromethorphan

• Dextromethorphan

• Coricidin Cough and Cold®

• CCC, Triple C, DXM, Poor Man’s PCP, Skittles, Robo

• Typically abused by teenagers

• Can be “free based” or taken orally in liquid/pill form

Dextromethorphan

• Mechanism of Action

• Acts in the medulla oblongata to raise the cough threshold (therapeutic)

• No activity at mu or delta receptors

• Antagonizes serotonin receptors

• Metabolized to dextrophan

• Acts like PCP and ketamine

• Non‐competitively antagonizes the NMDA receptor

Amaladoss A, et al. Can J Emerg Med. 2011;13(1):53‐56. Cooper RJ. J Subst Abuse. 2013;18(2):82‐107.Bryner JK, et al. Arch Pediatr Adolesc Med. 2006;160(12):1217‐1222. Reissig CJ, et al. Psychopharmacology (Berl). 2012;223(1):1‐15. Logan BK, et al. J Forensic Sci. 2012;57(5):1388‐94. Bodmer M. Br J Clin Pharmacol. 2010;70(6):794‐798,Romanelli F, et al. Pharmacy Today. 2009;15(3):48‐55. Burns JM, et al. Sub Abuse and Rehab. 2013;4:75‐82.

DextromethorphanDoses

• Stage 1 (1.5‐2.5 mg/kg)

• Increased alertness

• Restlessness

• Visual and auditory sensitization

• Generalized euphoria

• Stage 2 (2.5‐7.5 mg/kg)

• Exaggerated auditory and visual sensations

• Hallucinations

• Increased energy

• Stage 3 (7.5‐15 mg/kg)

• Visual and auditory disturbances

• Impaired cognition

• Mania

• Partial disassociation

• Stage 4 (>15 mg/kg)

• Complete disassociation

• Hallucination/delusions

• Ataxia


Dextromethorphan• Bromide Toxicity

• Effects seen at levels >50‐100 mg/dL

• CNS effects

• Hypotension

• Tachycardia

• Chronic abuse

• Serotonin Syndrome

• Altered mental status

• Rigidity

• Hyperthermia

• Seizures

• Drug interactions –serotonergic drugs

• Caution: Co‐ingestants


Dextromethorphan

• Treatment

• Decontamination

• Activated charcoal• Agitation

• Lorazepam• Haloperidol, risperidone, quetiapine• Trazodone or sleep aid

• Naloxone (?)

• Treat serotonin syndrome if presentAmaladoss A, et al. Can J Emerg Med. 2011;13(1):53‐56. Cooper RJ. J Subst Abuse. 2013;18(2):82‐107.Bryner JK, et al. Arch Pediatr Adolesc Med. 2006;160(12):1217‐1222. Reissig CJ, et al. Psychopharmacology (Berl). 2012;223(1):1‐15. Logan BK, et al. J Forensic Sci. 2012;57(5):1388‐94. Bodmer M. Br J Clin Pharmacol. 2010;70(6):794‐798,Romanelli F, et al. Pharmacy Today. 2009;15(3):48‐55. Burns JM, et al. Sub Abuse and Rehab. 2013;4:75‐82.

Naturally Occurring Hallucinogens

• Lysergamides

• Morning glory (lpomoea violacea)

• Hawaiian baby woodrose (Argyreia nervosa)

• Psilocybin

• Found in some mushrooms‐ “magic mushrooms”

• Psilocybe caerulescens• Psilocybe cubensis• Panaeolus foenisecii• Conocybe cyanopus

• Amanita muscaria

• MushroomGoldfrank LR. (2010). Goldfrank’s Toxicologic Emergencies, 9th Edition: Mushrooms. New York: McGraw Hill Medical.Babu, K. (2010). Goldfrank’s Toxicologic Emergencies, 9th Edition: Hallucinogens. New York: McGraw Hill Medical.



• Toad‐licking

• Nutmeg

• Myristica fragrans

• Salvia

• Salvia divinorum

• Member of the mint family

• Jimson Weed

• Datura stramonium

Naturally Occurring Hallucinogens

Goldfrank LR. (2010). Goldfrank’s Toxicologic Emergencies, 9th Edition: Mushrooms. New York: McGraw Hill Medical.Babu, K. (2010). Goldfrank’s Toxicologic Emergencies, 9th Edition: Hallucinogens. New York: McGraw Hill Medical.

Naturally Occurring Hallucinogens:Lysergamides

• Morning Glory• Morning Glory: Seeds are chewed and swallowed or can

be ground into a drink• Commercial seeds are treated and cause severe nausea and vomiting

• Dose: 25‐50 seeds, most people use at least 100 seeds• Reports of 100‐400 seeds ingested by routine users

• Presentation• Onset usually within 1 hour of consumption• Similar to LSD

• Treatment• Similar to LSD (control agitation with benzodiazepines)

Babu, K. (2010). Goldfrank’s Toxicologic Emergencies, 9th Edition: Hallucinogens. New York: McGraw Hill Medical.

• “Magic Mushrooms”• Mushrooms are consumed or smoked• Psychoactive component

• Hydrolyzed into psilocin• Acts at 5‐HT2 receptor• Effects within 1 hour of ingestion• Presentation

• Hyperkinesis• Anxiety• Hallucinations• Renal failure• Seizures

• Treatment for agitation is benzodiazepines (supportive)

Naturally Occurring Hallucinogens: Psilocybins

Goldfrank LR. (2010). Goldfrank’s Toxicologic Emergencies, 9th Edition: Mushrooms. New York: McGraw Hill Medical.

• Sought out for hallucinogenic effects• Psychoactive component

• Small amounts of ibotenic acid and muscimol• Ibotenic acid: structurally similar to glutamic acid• Muscimol: similar to GABA

• Presentation:• Somnolence• Hallucinations• Seizures

• Treatment: benzodiazepines during excitatory phase (supportive)

Naturally Occurring Hallucinogens: Amanita muscaria

Goldfrank LR. (2010). Goldfrank’s Toxicologic Emergencies, 9th Edition: Mushrooms. New York: McGraw Hill Medical.

Naturally Occurring Hallucinogens: Toad Licking

• False information• Some toads contain bufotenin

• Does not cross blood brain barrier• No hallucinogenic effects

• Psychoactive component• 5‐MeO‐DMT in some secretions

• Bufo alvarius (Sonoran Desert toad/Colorado River toad)

• Extraction of the secretions for smoking is the only way to produce effects

• Problem…• Can cause cardiac toxicity

Babu, Kavita. (2010). Goldfrank’s Toxicologic Emergencies, 9th Edition: Hallucinogens. New York: McGraw Hill Medical.

• Psychoactive component• Myristicin

• Dose: 5‐30 g (1 tablespoon = 7 g)• Onset: 1 hour• Duration: 24 hours• Mechanism of action:

• Act at serotonin receptors (similar to amphetamines)

• Weak MAO‐I• Anticholinergic properties

Naturally Occurring Hallucinogens: Myristica fragrans

Mckenna A, et al. Eur J Emerg Med. 2004;11:240‐241.Forrester MB. Hum Exp Toxicol. 2005;24:563‐566.



• Presentation• Euphoria• Hallucinations• Drowsiness• Tachycardia/hypotension• Sweating• Hypothermia

• Treatment• Activated charcoal (?)• Benzodiazepines ‐ supportive

Naturally Occurring Hallucinogens: Myristica fragrans

Mckenna A, et al. Eur J Emerg Med. 2004;11:240‐241.Forrester MB. Hum Exp Toxicol. 2005;24:563‐566

Naturally Occurring Hallucinogens:Salvia divinorum

• Most potent of natural hallucinogens• Desired effect is achieved by chewing wet leaves

• Smoking dried leaves does not produce effect• Most people do not enjoy the effects• Dose: 15‐20 g chewed wet leaf (6‐30 leaves)

• Extract is available• Onset: immediate• Duration: 1‐2 hours• Psychoactive component

• Salvinorin A and B• Mechanism of action

• Binds to the kappa‐opioid receptor


• “Medicinal Purpose”• Depression

• Presentation• Diaphoresis• Hallucinations• “Catatonic state”• Psychosis• Emotional swings

• Treatment• Supportive

Naturally Occurring Hallucinogens:Salvia divinorum


Naturally Occurring Hallucinogens:Datura stramonium

• “Loco weed”• Psychoactive component

• Atropine, hyoscyamine, scopolamine• Seeds are ingested

• Abused by adolescents• Unintentional deaths from anticholinergic toxicity• Dose

• 10 seeds (ingested)• Onset: 20‐30 minutes


• Duration: 2‐3 hours• Presentation

• Hyperthermia• Tachycardia• Mydriasis• Hallucinations• Agitation• Delirium

• Treatment• Benzodiazepines• ** Physostigmine **

Naturally Occurring Hallucinogens:Datura stramonium


The Case Re‐visited…

Restrain the patient in hard restraints

Administer a benzodiazepine

Administer an antipsychotic

Do nothing and get a urine drug screen



The Late Rabbit: Stimulants

Philippe Mentler PharmD BCPSPharmacy Implementation Manager

VHA Inc.

Case

© Milosducati | Dreamstime.com ‐ Chest Pain Photo

• 32 YO male presents with chest pain and anxiety

• Admits to cocaine use prior to arrival

CASE Case

• 32 YO male presents with chest pain andanxiety after cocaine use

• Vitals: RR:20 HR:104 BP:189/98 Temp:100.1 F

• Pupils dilated

• Visibly anxious, restless, perspiring

• Pain: 10/10, diffuse, radiates to jaw

• STAT ECG ordered

What initial pharmacologic interventions should be taken?

Case

• 32 YO male presents with chest pain andanxiety after cocaine use

• Vitals: RR:20 HR:104 BP:189/98 Temp:100.1 F

• Pupils dilated

• Visibly anxious, restless, diaphoretic

• Pain: 10/10, diffuse, radiates to jaw

The sympathimometic toxidrome

What is the initial pharmacologic intervention?

Metoprolol 5mg IV, nitroglycerin 0.4mg SL, lorazepam2mg (or equivalent) IV, aspirin

Labetalol 20mg IV, nitroglycerin 0.4mg SL, aspirin

Nitroglycerin 0.4mg SL, lorazepam 2mg (or equivalent) IV, aspirin

Midazolam 5mg IM



Stimulants General Mechanisms

• Enhances synaptic availability of neurotransmitters

• Type and amount depends on stimulant

• Epinephrine

• Norepinephrine

• Dopamine

• Serotonin

Stimulants General Mechanisms

• Effects both centrally and peripherally

• CNS mediated effects

• Euphoria, reduced inhibition, agitation, psychosis, seizures

• Peripherally mediated effects

• Hypertension, tachycardia, dysrhythmias, hyperthermia, diaphoresis

Cocaine

• Street Names:

• Coke, blow, snow, nose candy ,bump, toot

• Medicinal Value: CII

• Local anesthetic and vasoconstrictive

• Nose bleeds

• Absorbed by mucosal surfaces or injected

• Onset ~2 minutes when snorted

• Duration ~30‐60 minutes

© Robotek | Dreamstime.com Drug Trafficking Photo

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Cocain

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Crack Cocaine

• “Freebase” form of cocaine

• Cocaine cooked in a base (NaHCO3)

• Can be smoked or injected

• quicker onset, shorter duration

• Cheaper

http://commons.wikimedia.org/wiki/Category:Crack_cocaine#mediaviewer/File:Rocks_of_crack_cocaine.jpg

Cocaine: Presentation

• Chest Pain: most common ED presentation

• Vasospasm and accelerated atherogenesis

• Hypertensive crises

• Dysrhythmias

• Seizures

• Dose dependant anxiety, agitation, hallucinations

What if…



Methamphetamine

• Street names

• Meth, crank, ice, chalk, glass, speed

• Regional problem but national concern

PD‐USGOV‐DEA

http://www.drugabuse.gov/sites/default/files/cewg_jan2014_execsumm.pdf

San DiegoSan FranciscoLos Angeles

Atlanta

United States

MiamiNYCPhiladelphiaDCBostonChicago

Why Meth (vs Cocaine)

• Cheap

• Can be used by many routes

• Oral, Intravenous, Inhalational

• Lasts longer than cocaine

• T1/2: 19‐34 hours

• Several hours (smoked)

• Easy and cheap to make

PD‐USGOV

Meth Presentation (vs Cocaine)

• Presentation primarily to CNS Effects

• Paranoia, psychosis, frequently violent

• Seizures less common

• Chest Pain less common

• Dysrhythmias less common

http://copypast.ru/2009/07/18/page,2,smotret_sjuda_ulybatelnaja_podborka.html

Other Stimulants

• Khat: plant based

• Synthetic Cathinones “Bath Salts, Ivory Wave”

• Mephedrone

• MDPV “Molly”

• Methylone “MDMC, bk‐MDMA,

Explosion, Molly”

• MDMA “Ecstasy, Molly, X, Adam”

• Prescription stimulants

Managing Stimulant Toxicity

• Symptom specific supportive care

• Chest Pain

• Dysrhythmias

• Hypertension

• Hyperthermia

• Anxiety

• Seizures

• Psychosis




• Chest Pain

• Benzodiazepines

• Nitrates

• Hypertension

• Benzodiazepines

• Calcium Channel Blockers

• Phentolamine

• NO BETA‐BLOCKER (BB) in acute toxicity

• Chart Review of 376 subjects with positive urine for cocaine.

• 166 got BB within 24 hours of presentation

• Results: No difference in efficacy/safety when BB’s used vs not used

• Authors: “BB treatment in cocaine‐induced chest pain may be safer than previously stated”

Am J Cardiol 2014;113:1802‐1806

• Phil’s retort (backed by Hoffman, Howland, et al)

• Duration of cocaine action is 2 hours

• Cocaine urine tests can remain positive for 72+ hours

• Beta Blocker admin could have been delayed up to 24 hours after presentation

• Value on BB administration in ED for ACS is in question

Am J Cardiol 2014;113:1802‐1806, Am J Emer Med 2013; 31: 983–994


• Tachycardia

• Benzodiazepines IV

• Hydration

• Dysrhythmias

• Atrial: Diltiazem IV or equivalent (no BB)

• Ventricular

• Bicarbonate IV

• Lidocaine IV


• Hyperthermia

• Benzodiazepines

• Hydration: goal urine output 1‐2ml/kg/hr

• Seizures

• Benzodiazepines, propofol

• Agitation, Psychosis

• If Violent: Midazolam 5mg IM

• Benzodiazepines (rapid titration)

Back to Case

32 YO male presents with chest pain and anxiety

A. Give aspirin 325mg PO, metoprolol 5mg IV, nitroglycerin 0.4mg SL, lorazepam 2mg IV

B. Give aspirin 325mg PO, labetalol 20mg IV, nitroglycerin 0.4mg SL

C. Give aspirin 325mg PO, nitroglycerin 0.4mg SL, lorazepam 2mg IV

D. Give midazolam 5mg IM



Back to the Case

32 YO male presents with chest pain and anxiety

Metoprolol 5mg IV, nitroglycerin 0.4mg SL, lorazepam 2mg (or equivalent) IV, aspirin

Labetalol 20mg IV, nitroglycerin 0.4mg SL, aspirin

Nitroglycerin 0.4mg SL, lorazepam 2mg (or equivalent) IV, aspirin

Midazolam 5mg IM

References• Bajaj NJ, D’Angelo T, Howland M, Hoffman M, et al. The In response to “Safety of beta‐blockers in the acute management of cocaine‐

associated chest pain”. American Journal of Emergency Medicine. 2013; 31(6 ):986 – 987

• Baumann BM, Perrone J, Hornig SE, et al. Randomized, double‐blind, placebo‐controlled trial of diazepam, nitroglycerin, or both for treatment of patients with potential cocaine‐associated acute coronary syndromes. Acad Emerg Med. 2000;7:878–85.

• Chiang WK. Amphetamines. In LR Goldfrank (ed), Goldfrank's toxicologic emergencies. New York : McGraw‐Hill Medical, c2011

• Fanari Z, Kennedy KK, Lim MJ, Laddu AA, Stolker JM. Comparison of in‐hospital outcomes for beta‐blocker use versus non‐beta blocker use in patients presenting with cocaine‐associated chest pain. Am J Cardiol. 2014;113(11):1802‐6.

• Hoffman RS, Prosser JM. Cocaine. In LR Goldfrank (ed), Goldfrank's toxicologic emergencies. New York : McGraw‐Hill Medical, c2011

• Ibrahim M, Maselli DJ, Hasan R, Hamilton A. Safety of beta‐blockers in the acute management of cocaine‐associated chest pain. Am J of Emerg Med.2013; 31:613–616.

• Maraj S, Figueredo VM, Morris DL. Cocaine and the Heart. Clin.Cardiol. 2010;33(5):264–269

• Martel M, Sterzinger A, Miner J, Clinton J, Biros M. Management of Acute Undifferentiated Agitation in the Emergency Department: A Randomized Double‐ Blind Trial of Droperidol, Ziprasidone, and Midazolam. Acad Emerg Med. 2005;12(12):1167‐1172

• Matsumoto RR, Seminerio MJ, Turner RC, Robson MJ, Nguyen L, Miller DB,O'Callaghan JP. Methamphetamine‐induced toxicity: An updated review on issuesrelated to hyperthermia. Pharmacol Ther. 2014 Oct;144(1):28‐40.

• McCord J, Jneid H, Hollander JE, et al. Management of cocaine‐associated chest pain and myocardial infarction: a scientific statement from the American Heart Association acute cardiac care committee of the council on clinical cardiology. Circulation 2008;117(14):1897–907.

• Paillet‐Loilier M, Cesbron A, Le Boisselier R, Bourgine J, Debruyne D. Emerging drugs of abuse: current perspectives on substituted cathinones Substance Abuse and Rehabilitation 2014:5 37–52.

• Panenka WJ, Procyshyn RM, Lecomte T, MacEwan GW, Flynn SW, Honer WG, Barr AM Methamphetamine use: a comprehensive review of molecular, preclinical and clinical findings. Acad Emerg Med. 2000 Aug;7(8):873‐7.

• Spiller HA, Hays HL, Aleguas A Jr Overdose of drugs for attention‐deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management. CNS Drugs. 2013;27(7):531‐43.

• Weber JE, Chudnofsky CR, Boczar M, Boyer EW, Wilkerson MD, Hollander JE. Cocaine‐associated chest pain: how common is myocardialinfarction?

• Zimmerman JL. Cocaine Intoxication. Crit Care Clin.2012;28:517–526.

The Smoking Caterpillar: Opiates and Depressants

Philippe Mentler PharmD BCPSPharmacy Implementation Manager

VHA Inc.

• EMS presents with a 32 yo ♂ who has who was found unresponsive. He is noted to have several dime sized scars all over his body and a tattoo of a monkey on his back.

• BP: 100/64 HR: 68 RR: 6 O2 Sat: 70% RA

• Pupils: pinpoint, equal

Case


• BP: 100/64 HR: 68 RR: 6 O2 Sat: 70% RA


What is this likely a picture of?


• BP: 100/64 HR: 68 RR: 6 O2 Sat: 70% RA


Case

The opiate toxidrome

Other routes: Skin Popping

• SubQ injections

• Offers longer highs

• Done with heroin, cocaine and others

• Infections, scarring

© 2001‐2011, DermAtlas





• BP: 100/64 HR: 68 RR: 6 O2 Sat: 70% RA


Case


• BP: 100/64 HR: 68 RR: 6 O2 Sat: 70% RA



What are the initial pharmacologic interventions?

Naloxone 0.04mg‐0.08mg IV q30sec

Naloxone 2mg IV q2min

Flumazenil 0.2mg IV q2min

Intubate first, then give naloxone 0.4mg IV

Heroin

• Street Names: Dope, Junk, Smack, H

• Commonly insufflated or injected in USA

• Injection declined at onset of HIV/AIDS

• Can be smoked: “chasing the dragon”

http://commons.wikimedia.org/wiki/Heroinhttp://commons.wikimedia.org/wiki/File:Heroin_asian.jpg

Heroin is a problem

• 17 of 20 Community Epidemiology Work Group (CEWG) regions believe heroin is, “the most, or one of the most, important drug abuse concerns affecting their area”

Opiate Toxicity Presentation

• Classic Triad: miosis, respiratory depression, altered mental status

• Others

• Bradycardia

• Hypotension

• Hypothermia

• Also: consider toxicity from combination Rx products

Managing Opioid Toxicity

• Naloxone: the wonder drug

• Onset: 1‐2 minutes

• Dosing (IV): what’s your goal?

• 2mg bolus almost always too much

• Can cause acute withdrawal

• May unmask co‐ingestants

• Opioid dependent: 0.04mg 0.08mg 0.4mg Q30sec then 2mg Q1min



Managing Opioid Toxicity

• What about other routes?

• Intranasal, SubQ, IM possible but slower and less predictable

• What about a Naloxone Drip?

• Consider if long acting opioid or recurrent respiratory depression

• Start at 2/3 the effective bolus dose per hour

• NOTE: only a starting point, intensive monitoring is still required

What if…

http://upload.wikimedia.org/wikipedia/commons/d/d8/Bolletjes.jpg

Body Packers/Drug Mules

• Smuggle “professionally” packaged drugs across borders

• Done with heroin, cocaine and others

• Treatment

• GI Decontamination:

• PEG‐3350 2 liters q1h until all packets out

• +/‐ Activated charcoal

• If symptomatic: Naloxone if opiate. Immediate surgical intervention if cocaine.

N Engl J Med. 2003;349(26): 2519–26

What if…

http://www.proceso.com.mx/?p=361469

Desomorphine

• Street Name: Krokodil (homemade desomorphine)

• Made from mixing Codeine with gasoline, HCL, iodine, phosphorus and paint thinner

• Cheaper than Heroin

• Problem in Russia

• 100,000 users

• Life expectancy after starting drug: 2‐3 years

• Cases reported in the US, not lab confirmed

• Primary concern is tissue necrosis/infection

Life Sciences 102 (2014) 81–87, Am J Med.2014;127(7):e25

Heroin is a problem but…

• 17 of 20 Community Epidemiology Work Group regions believe heroin is, “the most, or one of the most, important drug abuse concerns affecting their area”

Figure 3. Drug-Related Emergency Department (ED) Visits, by Type of Visit: 2004 to 2009*



Sedative‐Hypnotics

• Benzodiazepines

• Mortality rare with lone benzo ingestions

• Respiratory depression is rare

• General Supportive care

• Flumazenil generally not recommended

• Exception would be in benzo naïve overdoses

Sedative‐Hypnotics

• Barbiturates

• Can cardiovascular collapse and respiratory arrest

• Hypothermia may be noted

• Blisters may be noted

• Treatment is supportive care

• Airway support

• Hemodynamic support

What are the initial pharmacologic interventions?

Naloxone 0.04mg‐0.08mg IV q30sec

Naloxone 2mg IV q2min

Flumazenil 0.2mg IV q2min

Intubate first, then give naloxone 0.4mg IV

Back to the Case

• EMS presents with a 32 yo ♂ who has who was found unresponsive.

• EDRPh recommends naloxone 0.04mg IV to start but MD wants 2mg IV

• RN gives 2mg, pt wakes and becomes violent

• Assaults 2 nurses and the pharmacist before security arrives

• Moral of the Story?

References• Boyer EW. Management of opioid analgesic overdose. N Engl J Med. 2012 Jul12;367(2):146‐55.

• Cantwell K, Dietze P, Flander L. The relationship between naloxone dose andkey patient variables in the treatment of non‐fatal heroin overdose in theprehospital setting. Resuscitation. 2005 Jun;65(3):315‐9.

• Davis CS, Banta‐Green CJ, Coffin P, Dailey MW, Walley AY. Intranasal Naloxonefor Opioid Overdose Reversal. Prehosp Emerg Care. 2014 Aug 25.

• Dixon P. Managing acute heroin overdose. Emerg Nurse. 2007 May;15(2):30‐5.

• Erickson TB, Thompson TM, Lu JJ. The Approach to the Patient with an Unknown Overdose. Emerg Med Clin N Am. 2007;25:249–281.

• Katselou M, Papoutsis J, Nikolaou P, Spiliopoulou C, Athanaselis S. A “Krokodil” emerges from the murky waters of addiction. Abuse trends of an old drug. Life Sciences. 2014; 102:81–87.

• Kerr D, Dietze P, Kelly AM. Intranasal naloxone for the treatment of suspectedheroin overdose. Addiction. 2008 Mar;103(3):379‐86.

• Kreshak AA, Cantrell FL, Clark RF, Tomaszewski CA. A poison center's ten‐year experience with flumazenil administration to acutely poisoned adults. J EmergMed. 2012 Oct;43(4):677‐82..

• Lee DC, Ferguson KL. Sedative‐Hypnotics. In LR Goldfrank (ed), Goldfrank's toxicologic emergencies. New York : McGraw‐Hill Medical, c2011

• Matsumoto RR, Seminerio MJ, Turner RC, Robson MJ, Nguyen L, Miller DB,O'Callaghan JP. Methamphetamine‐induced toxicity: An updated review on issuesrelated to hyperthermia. Pharmacol Ther. 2014 Oct;144(1):28‐40.

• Mullins ME, Schwarz ES, To the Editor: ‘Krokodil’ in the United States Is an Urban Legend and Not a Medical Fact “The American Journal of Medicine. 2014;127(7):e25.

• Nelson LS, Olson D. Opioids. In LR Goldfrank (ed), Goldfrank's toxicologic emergencies. New York : McGraw‐Hill Medical, c2011

• Ngo AS, Anthony CR, Samuel M, Wong E, Ponampalam R. Should a benzodiazepineantagonist be used in unconscious patients presenting to the emergencydepartment? Resuscitation. 2007 Jul;74(1):27‐37.

• Panenka WJ, Procyshyn RM, Lecomte T, MacEwan GW, Flynn SW, Honer WG, Barr AM. Methamphetamine use: a comprehensive review of molecular, preclinical andclinical findings. Drug Alcohol Depend. 2013 May 1;129(3):167‐79.

• Sabzghabaee AM, Eizadi‐Mood N, Yaraghi A, Zandifar S. Naloxone therapy inopioid overdose patients: intranasal or intravenous? A randomized clinical trial.Arch Med Sci. 2014 May 12;10(2):309‐14.

• Seger DL. Flumazenil‐‐treatment or toxin. J Toxicol Clin Toxicol.2004;42(2):209‐16.

• Traub SJ, Hoffman RS, Nelson LS. Body Packing‐The Internal Concealment of Illicit Drugs. NEJM.2003;349(26):2519‐252.

• Veiraiah A, Dyas J, Cooper G, Routledge PA, Thompson JP. Flumazenil use inbenzodiazepine overdose in the UK: a retrospective survey of NPIS data. Emerg MedJ. 2012 Jul;29(7):565‐9.

Key Takeaways• Key Takeaway #1

• Most hallucinogen overdoses can be managed with supportive care including benzodiazepines

• Caution with co‐ingestants• Key Takeaway #2

• Cocaine is to cardiovascular issues like methamphetamine is to behavior issues

• Key Takeaway #3

• Naloxone is very effective so use carefully

• Start with low doses in opioid dependant cases• Always consider co‐ingestants



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