Update in Toxicology 2 013 K2, Spice, Bath

Update in Toxicology 2 013 K2, Spice, Bath

Update in Toxicology 2 013 K2, Spice, Bath Salts, & the New Designer Dr ugs William Hurley, MD FACEP Harborview Medical Cente r Washington Poison Center [email protected] [email protected]

(800) 222-1222 (800) 709-0911 Update in Toxicology 201 3 Goal Increase knowledge in managemen t of the poisoned patient

Objectives Describe manifestations & manage ment of the stimulant syndrome List new designer drugs, their mec hanisms, & their sources Designer Drugs Tox Update 2012 Designer Drugs Designer Drugs Poisoning Case

A 20 year-old female is found agitated & conf used by family in her dormitory room. She has no significant past medical history, b ut the family suspects she has been experi menting with alcohol & marijuana since star ting school. She is agitated & aggressively ordering care providers to leave her exam room. Family ex plains this is not like her at all. She is tachycardic, hypertensive, hot, & diap horetic

(P 128, BP 180/110) Designer Drugs How would you manage this encounter? 20 Year Old Female Anxious & Agitated Initial Evaluation ? Designer Drugs

20 Year Old Female Anxious & Agitated Mental Status A B C D E

Designer Drugs 20 Year Old Female Anxious & Agitated Mental Status A Open & Protected ? B Ventilating & Oxygenating ? C Rhythm, Perfusion ?

D - Disability / Seizures Decontamination, Dextrose ? E Exposure, Elimination ? Poison Center 1-800-222-1222 Designer Drugs Initial Management Airway

Breathing Circulation WA Poison Cen ter 1-800-222-122 2 80% of poisonings 1-800-709-091 Disability/Decontami 1 nation 90% of poisonings

Exposure/Elimination Antidotes Designer Drugs 100% of poisonings 20 Year Old Female Anxious & Agitated

Agitated, responding to loud verb al A Open with intact gag reflex B - RR 20-24 / minute, clear lungs C - Tachycardic (Sinus - 130s) Hypertensive (180/110) D - No Seizure, Glucose 108 Decontamination? E Elimination? Designer Drugs Poisoning Managemen t

ABCDE Safety Net IV, Monitors (ECG & O2) Focused History What, when, why, what has been done? What else is available? Focused Physical Examination Toxicologic Syndrome? Designer Drugs

Toxicologic Syndromes Serotonergic Asphyxiant Hepatotoxic Cholinergic Anticholinergic Heavy Metal

Cyclic Antidepr Irritant gas Caustic essant Salicylates Opiod Toxic Alcohols Sedative Hydrocarbons Stimulant Hallucinogenic Designer Drugs Calcium antag Poisoning Managemen t

Physical Examination Toxicologic Syndro me Designer Drugs Poisoning Managemen t Physical Examination Toxicologic Syndro me Vital Signs Mental Status

confused, stimulated, depressed Pupils; small or large, reactive or not Mucus membranes; color, moisture Respiratory rate & depth, bronchospasm, pulmonary edema Gastrointestinal Tract; hyper- or hypoactive Skin; color, temperature, moisture Designer Drugs Poisoning Case

A 20 year-old female craz y Tachycardic, hypertensive, warm, & wet (P 130, BP 185/110) Synthetic marijuana? Designer Drugs Poisoning Case

A 20 year-old female cra zy Tachycardic, hypertensiv e, warm, & wet (P 130, BP 185/110) Synthetic marijuana? Toxicologic Syndrome? Designer Drugs

Physical Examination Stimulant Syndrome Vital Signs T, P, R, BP

Mental Status Seizures Dilated & react Pupils ive Mucus membra Moist nes Respiratory Rate, depth Gastrointestina Motility Pink, warm, mo l Designer Drugs

Skin ist Spice Case Roomate produces packets of ince nse purchased at a local head sh op. Designer Drugs Designer Drugs Spice Case

A 20 year-old female crazy Begins screaming & struggling Attempting IV Has 3 minute seizure Management? Designer Drugs Stimulant Agents - ? Designer Drugs

Stimulant Agents Cocaine Amphetamines Methamphetamine, Ecstasy, methylphenidate, phentermi ne Decongestants Ephedrine, Pseudo-ephedrin e

Beta Stimulators Albuterol, caffeine, theophyll ine Designer Drugs Withdrawal States Designer Drugs

Cannabinoids Cannabinoids Spice products - Europe in 2004 Herbal smoking blend Not for Human Consumption Synthetic agents, created to simul ate effects of cannabis

CNS cannabinoid receptors Derived from cathinones (Khat) Designer Drugs Cannabinoids Sold in small pack ets Variety of names K2, Spice Gold, S pice Diamond, Spi

ce Silver, Spice of Life Retail U. S. $25-$ 40 Designer Drugs Plant & Herbal Blends

Marketed as incen se Desire for legal hi gh Ability to avoid det ection on drugs-ofabuse testing (TH C) Designer Drugs Whats up with the Ey e? Designer Drugs Whats up with the Ey

e? Wide-open-eye i mprint Allusion to Dun e Fictional drug M

elange Called the spice Excessive useDesigner ca Drugs Cannabinoids Heterogeneous structured compo unds Agonize endogenous cannabinoid re ceptors Include phytocannabinoids derived fr om Cannabis sativa (delta 9-THC) Endogenous cannabinoids

Synthetics Designer Drugs Synthetic Cannabinoid s Synthesized 1960s at Hebrew University (H U) HU-210

Pfizer 1970s; Cyclohe xylphenol series J W Huffman (JWH) 80 s JWH-018, JWH-073, Designer Drugs JW Cannabinoids Signs & Symptoms

Tachycardia Hypertension Hyperthermia Anxiety Seizures Paranoia & hallu cinations Designer Drugs European Ex perience

Within weeks of regulatory contr ol Non-prohibited c annabinoids fou nd in products Structures heter ogeneous No THC rxn Designer Drugs Synthetic Cannabinoid s 2010

JWH 250 13% JWH 73 11% U.S. DEA, Office of Diversion Control U.S. DEA Activity March, 2011 Temporary Schedule I unsafe, highly abused, no medical usa ge

Five synthetic cannabinoids JWH-018, JWH-073, JWH-200 CP-47,497 & Cannabicyclohexanol HU-210 all ready Schedule I Designer Drugs Synthetic Cannabinoid s 2011 JWH 250 12% AM-2201 29%

JWH 210 9% JWH-122 12% U.S. DEA, Office of Diversion Control JWH-18 14% Synthetic Drug Abuse Prevention Act of 2012 Signed into law July 9, 2012

Adds certain classes of synthetic cannabinoids & two substituted c athinonesmephedrone and MDP Vto the federal controlled subst ances act. Designer Drugs Designer Drugs Stimulant Agents

Cocaine Amphetamines Decongestants Beta Stimulators Withdrawal States Cannabinoids JWH-018, JWH-073, JWH-200 CP-47,497, Cannabicyclohexan ol HU-210 Designer Drugs Stimulant Agents Mechanisms of Action - ?

Designer Drugs Stimulant Agents Mechanisms of Action Stimulant Agents Mechanisms of Action Central inhibition of catecholamin e reuptake Epinephrine, norepinephrine

Peripheral stimulation of alpha & beta receptors Additional effects (nuances) Na channel / local anesthetic (cocain e) Serotonin reuptake inhibition (MDM A) Designer Drugs Designer Drugs Stimulant Toxicity Clinical Management - ? Designer Drugs

Stimulant Toxicity Clinical Management Central inhibition of catecholamine reup take Benzodiazepines (GABA receptor agonists) 0.1-0.2 mg/kg Diazepam IV (5-10 mg) 0.05 mg/kg Lorazepam or Midazolam IV o r IM (2-5 mg) Repeat every 5-10 minutes for seizures, every 10 minutes until calm Neuroleptics (monitor the QT interval) 2-5 mg IM or slow IV Haloperidol or Drop eridol

Designer Drugs Stimulant Toxicit y Management Peripheral stimulatio n of alpha & beta rec eptors Benzodiazepines (ca rdiac receptors) Vasodilators; phentola mine, nitroprusside Cardiac monitoring

Additional effects Benzodiazepines Hydration, Cooling, Ne uromuscular paralysis Designer Drugs Spice Case A 20 year-old female cra zy

Tachycardic, hypertensiv e, warm, & wet (P 140, BP 185/110) Diazepam 5 mg IV X 2 Temp 104.4o Urine reddish brown IV NS with 2 amps NaHC O3 Designer Drugs Spice Case

CT head negative Urine Tox negative Admitted ICU Continuous EEG moni toring Awakens next morni ng Admits binge of Spic e Peak CPK 14,000

No renal failure Designer Discharged home int Drugs Smoking Bath Sal ts 26 y.o. male a gitated & confuse d 3 day binge

Smoking Bolivi an Bath Salts Roomate found him face-down on floor Designer Drugs 26 Year Old Male Agitated & Confused Management?

Designer Drugs Initial Management Airway Breathing Circulation WA Poison Cen ter 1-800-222-122

2 80% of poisonings 1-800-709-091 Disability/Decontami 1 nation 90% of poisonings Exposure/Elimination Antidotes Designer Drugs 100% of poisonings

26 Year Old Male Agitated & Confused Agitated, responding to loud verb al A Open with intact gag reflex B - RR 28 / minute, clear lungs C - Tachycardic (Sinus - 130s)

Hypertensive (160/100) D - No Seizure, Glucose 120 Decontamination? E Elimination? Designer Drugs Bath Salts Case Agitated, responds to loud verbal sti muli

No trauma Pupils 6 mm P 130 BP 160/100 Diaphoretic & Hot Designer Drugs Physical Examination Stimulant Syndrome

Vital Signs T, P, R, BP Mental Status Seizures Dilated & react Pupils ive Mucus membra Moist nes

Respiratory Rate, depth Gastrointestina Motility Pink, warm, mo l Designer Drugs Skin ist Bath Salts White Ice, Ocean Sno w, Lunar Wave, Purple

Wave, Ivory Wave, Ivor y Soft, Vanilla Sky, Bliss $20 packets from conv enience stores, truck st ops & via Internet Designer Drugs Bath Salts - Compou nds Very similar to amphetamines Side effects largely the same we se e with amphetamines in large dose

Jeffrey Baldwin, University of Nebrask a Medical Center Typically snorted, smoked, injected Can be mixed with water as a beve rage Designer Drugs Snorting & Smoking Bath Salt s Designer Drugs

Bath Salts - Contents Mephedrone MDPV (3,4-methylenedioxypyrovaler one) Designer Drugs Mephedrone - Europe

Cathinone derivative Marketed as plant feeder not for human consum ption Potentially addictive & Increasingly popular legal substitute for cocaine & e cstasy Designer Drugs MDPV 3,4 methylendioxypyrovaler

one Epinephrine & Nor-epine phrine re-u ptake inhibi tor Designer Drugs MDPV 3,4 methylendioxypyrovaler one

Epinephrine & Norepinephrine re-up take inhibitor Beta ketone research chemical Intake (Dose 5-15 mg); Oral (capsule, bombing, beverage) Rectal, Insufflation, Smoking, IV Onset 1 hr, Peak 1.5 hr, Duration 3-12 hrs Designer Drugs MDPV Toxicity -?

Designer Drugs Bath Salts Toxicity 35 patients, Michigan EDs Agitation - 23 patients (66%) Tachycardia - 22 (63%) Delusions/hallucinations - 14 (40%) 17 patients hospitalized, 1 DOA MDPV Identified

MMWR / May 20, 2011 / Vol. 60 / No. 19 Designer Drugs Bath Salts Case Agitated for 18 hour

s at hospital Tachycardia resolves with IV benzos & flui ds Temp 104.1 Urine (+) benzos onl y CK Peak 6500 Designer Drugs Cannabinoids & Bath Salts 2010 - 2011 Olives TD, et al. Bath salts: the ivory wave of trouble. West J Emerg Med. 2012 Feb;13(1):58-62. Designer Drugs

Bath Salts - Banned DEA Temporary Schedule I (Oct 2 011) Up to 12 months for permanent Louisiana, Florida, North Dakota, WA New York, Kentucky, Mississippi - Pen ding

PC calls fell with Louisiana ban Now ordering by Internet Designer Drugs Shipping to Mississippi Stimulant Agents Cocaine Amphetamines

Decongestants Beta Stimulators Withdrawal States Cannabinoids Bath Salts Mephedrone MDPV Designer Drugs New Rave (2 C agent s) Minneapolis, MN 17 March 2011 Eleven hospitalized (16-21 y.o.) 2 critical, 1 dead

Konawa, OK 7 May 2011 Seven hospitalized (19-20 y.o.) 2 critical, 1 dead 2,5-dimethoxy-4-ethyl-phenethyla mine Designer Drugs 2, 5, I-NBOMe Deaths Erowid.org (Extracts)

March 2012 Adult male South A ustralia 2C-I-NBOMe & 2C-B-NBOMe (MVC) June 2012 17 & 18 yo males MN Mixed 25i with chocolate candy July 2012 - 25 yo female, NC 25i pills, died >12 hours after ingesti on Designer Drugs 2011

2 Ci Blotter Paper Designer Drugs Designer Drugs 2 C-I Designer Drugs Phenethylamines Chemical Name Street Name

3,4,5-trimethoxyphenethylamine Mescaline 2C-E 2,5-dimethoxy-4-ethylphenethylamine Europa 2C-B 2,5-dimethoxy-4-bromophenethylamine Bees, Bromo, Bromo mescaline, Nexus, Spectrum, Toonies, Venus

2C-I 2,5-dimethoxy-4-iodophenethylamine N-Bomb 2C-T7 2,5-dimethoxy-4- propylthio-phenethylamine Blue Mystic, Vanilla Aroma Designer Drugs Phenethylamine

s Agonist/antagonist 5-HT receptor Hallucinations Over-stimulation & agitation (ampheta mines) Multiple forms Tablets, capsules, powder for insufflati on Kinetics

Onset 20 min, peak 2 hrs, duration 6-1 Designer Drugs 2 hrs Designer Drugs Phenethylamines Clinical Effects Hallucinations, agitation, seizures Hyperthermia, tachycardia, hypertension, ta chypnea Extreme/rapid cycling emotions Mydriasis, flushing, diaphoresis Nausea, vomiting, Facial dystonia (teeth grinding, grimacing)

Rhabdomyolysis Designer Drugs Phenethylamines (con t) Insufflation - immediate pain nasal muc osa Law enforcement officers Phenethylamine laboratories Mucous membrane & respiratory symptoms Designer Drugs Phenethylamines

Legal control 2C-B & 2C-T7 Schedule I 2C-E & 2C-I - not scheduled controlled substance analogs Bad trips ?alleviated by SSRIs? Not studied nor recommended Designer Drugs Stimulant Agents

Cocaine Amphetamines Decongestants Beta Stimulators Withdrawal States Cannabinoids Bath Salts

Phenethylamines 2 CE & 2 CI Designer Drugs Stimulant Agents Mechanisms of Action Central inhibition of catecholamin e reuptake Epinephrine, norepinephrine Peripheral stimulation of alpha &

beta receptors Additional effects (nuances) Na channel / local anesthetic (cocain e) Serotonin reuptake inhibition (MDM A) Designer Drugs Poisoning Managemen t ABCDE Poison Center (1-800-222-1222) Safety Net IV, Monitors (ECG & O2)

Focused History What, when, why, what has been done? What else is available? Focused Physical Examination Toxicologic Syndrome? Laboratory Studies? Designer Drugs

Bath Salts and Stimulants Designer Drugs - E xpanded, Urine Test (8756U) Methamphetamine, Amphetamine, O-Desmethyltramadol MDMA, MDEA, MDA, DOM Mephedrone, MDPV, Pyrovalerone,, Ethylone, Flephedrone, Buph edrone, Methedrone, Methylone, Cathinone, Methcathinone 2C-B 2C-C 2C-E 2C-H 2C-I 2C-N 2C-P 2C-T-2 2C-T-7 Synthetic Cannabinoid Metabolites Screen - E xpanded, Urine (Forensic) Test (9562U) AM-2201, JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH210, JWH-250, & RCS-4 metabolites

Tox Update 2012 Stimulant Toxicity - Key Poi nts Central & Peripheral catecholamine surge Characteristic clinical toxicological syndrome Specific agents Cocaine, amphetamines, decongestants, cann abinoids, Mephedrone, MDPV, phenethylamine s Often unavailable for decontamination & detec

tion Treat the patient, not the agent Importance - reduce severity of poisoning (avoid complications) Designer Drugs Benzodiazepines & Hyperthermia prevention Spice References Gunderson EW, et al. "Spice" and "K2" herbal high s: a case series and systematic review of the clinic al effects and biopsychosocial implications of synt hetic cannabinoid use in humans. Am J Addict. 20

12 Jul-Aug;21(4):320-6. Simmons JR, et al. Intoxication from smoking "spic e. Ann Emerg Med. 2011 Feb;57(2):187-8. Vardakou I, et al. Spice drugs as a new trend: mod e of action, identification & legislation. Toxicol Lett 2010 Sep 1;197(3):157-62. Schneir AB, et al. "Spice" Girls: Synthetic Cannabi noid Intoxication. J Designer Emerg Med 2010 Dec 15. Drugs Bath Salts - Referen ces o Borek HA, et al. Hyperthermia and multiorgan failure after o

o o o abuse of "bath salts" containing 3,4methylenedioxypyrovalerone. Ann Emerg Med. 2012 Jul;60(1):103-5. Prosser JM, Nelson LS. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol. 2012 Mar;8(1):33-42. Murray BL, et al. Death following recreational use of designer drug "bath salts" containing 3,4Methylenedioxypyrovalerone (MDPV). J Med Toxicol. 2012 Mar;8(1):69-75. Kasick DP, et al. "Bath salt" ingestion leading to severe intoxication delirium: two cases and a brief review of the

emergence of mephedrone use. Am J Drug Alc Abuse. 2012 Mar;38(2):176-80. Emergency department visits after use of a drug sold as Designer Drugs "bath salts"--Michigan, November 13, 2010-March 31, Update in Toxicology 201 3 Goal Increase knowledge in management of the poisoned patient

Objectives Describe manifestations & managem ent of the stimulant syndrome List new designer drugs, their mecha nisms, & their sources Designer Drugs Update in Toxicology 2 013 K2, Spice, Bath Salts, & the New Designer Dr ugs

William Hurley, MD FACEP Harborview Medical Cente r Washington Poison Center [email protected] [email protected] (800) 222-1222 (800) 709-0911

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