Update in Toxicology 2013 K2, Spice, Bath Salts,

& the New Designer Drugs

William Hurley, MD FACEP Harborview Medical

Center Washington Poison Center

– hurleyw@uw.edu– hurley@wapc.org– (800) 222-1222– (800) 709-0911

Update in Toxicology 2013 Goal

– Increase knowledge in management of the poisoned patient

Objectives– Describe manifestations &

management of the stimulant syndrome

– List new designer drugs, their mechanisms, & their sourcesDesigner Drugs

Tox Update 2012

Designer Drugs

Designer Drugs

Designer Drugs

Poisoning Case A 20 year-old female is found agitated &

confused by family in her dormitory room. She has no significant past medical history,

but the family suspects she has been “experimenting” with alcohol & marijuana since starting school.

She is agitated & aggressively ordering care providers to leave her exam room. Family explains this is not like her at all.

She is tachycardic, hypertensive, hot, & diaphoretic – (P 128, BP 180/110)

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 1-800-222-1222Designer Drugs

Initial Management WA Poison

Center 1-800-222-

1222 1-800-709-

0911

Airway Breathing Circulation

– 80% of poisonings Disability/

Decontamination– 90% of poisonings

Exposure/Elimination– Antidotes– 100% of poisoningsDesigner Drugs

20 Year Old Female Anxious & Agitated Agitated, responding to loud

verbal A – Open with intact gag reflex B - RR 20-24 / minute, clear lungs C - Tachycardic (Sinus - 130’s)

Hypertensive (180/110) D - No Seizure, Glucose 108 Decontamination? E – Elimination?

Designer Drugs

Poisoning Management

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 Asphyxiant Cholinergic Anticholinergic Cyclic

Antidepressant Opiod Sedative Stimulant Hallucinogenic

Serotonergic Hepatotoxic Heavy Metal Irritant gas Caustic Salicylates Toxic Alcohols Hydrocarbons Calcium

antagonistsDesigner Drugs

Poisoning Management

Physical Examination – Toxicologic Syndrome

Designer Drugs

Poisoning Management

Physical Examination – Toxicologic Syndrome– 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, moistureDesigner Drugs

Poisoning Case A 20 year-old female

“crazy” Tachycardic, hypertensive,

warm, & wet – (P 130, BP 185/110)

Synthetic marijuana?

Designer Drugs

Poisoning Case A 20 year-old female

“crazy” Tachycardic,

hypertensive, warm, & wet – (P 130, BP 185/110)

Synthetic marijuana? Toxicologic Syndrome?

Designer Drugs

Physical ExaminationStimulant Syndrome Vital Signs Mental Status Pupils Mucus

membranes Respiratory Gastrointestina

l Skin

T, P, R, BP Seizures Dilated &

reactive Moist Rate, depth Motility Pink, warm,

moistDesigner Drugs

Spice Case Roomate produces packets of

incense purchased at a local “head shop.”

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, phentermine

Decongestants– Ephedrine, Pseudo-

ephedrine Beta Stimulators

– Albuterol, caffeine, theophylline

Withdrawal States– EtOH, benzodizepine, GHB

Designer Drugs

Designer Drugs

Cannabinoids

Cannabinoids Spice products - Europe in 2004 “Herbal smoking blend” “Not for Human Consumption” Synthetic agents, created to

simulate effects of cannabis CNS cannabinoid receptors

Derived from cathinones (“Khat”)Designer Drugs

Cannabinoids Sold in small

packets Variety of names

– K2, Spice Gold, Spice Diamond, Spice Silver, Spice of Life

Retail U. S. $25-$40

Designer Drugs

Plant & Herbal Blends Marketed as

incense Desire for ‘legal

high’ Ability to avoid

detection on drugs-of-abuse testing (THC)

Designer Drugs

What’s up with the Eye?

Designer Drugs

What’s up with the Eye? Wide-open-eye

imprint Allusion to

‘‘Dune’’ Fictional drug

‘‘Melange’’ Called ‘‘the

spice” Excessive use

caused blue sclera

Designer Drugs

Cannabinoids Heterogeneous structured

compounds– Agonize endogenous cannabinoid

receptors– Include phytocannabinoids derived

from Cannabis sativa (delta 9-THC)– Endogenous cannabinoids– Synthetics

Designer Drugs

Synthetic Cannabinoids Synthesized 1960s at

Hebrew University (HU)– HU-210

Pfizer 1970s; Cyclohexylphenol series

J W Huffman (JWH) 80s– JWH-018, JWH-073,

JWH-200

Designer Drugs

Cannabinoids Signs & Symptoms

Tachycardia Hypertension Hyperthermia Anxiety Seizures Paranoia &

hallucinationsDesigner Drugs

European Experience Within weeks of

regulatory control

Non-prohibited cannabinoids found in products

Structures heterogeneous– No THC rxn

Designer Drugs

Synthetic Cannabinoids 2010

U.S. DEA, Office of Diversion Control

JWH – 7311%

JWH – 25013%

U.S. DEA Activity March, 2011 Temporary Schedule I

– unsafe, highly abused, no medical usage

Five synthetic cannabinoids– JWH-018, JWH-073, JWH-200– CP-47,497 & Cannabicyclohexanol– HU-210 all ready Schedule I

Designer Drugs

Synthetic Cannabinoids 2011

U.S. DEA, Office of Diversion Control

JWH – 25012%

JWH – 2109%

JWH-12212%

JWH-1814%

AM-220129%

Synthetic Drug Abuse Prevention Act of 2012 Signed into law July 9, 2012 Adds certain classes of synthetic

cannabinoids & two substituted cathinones —mephedrone and MDPV—to the federal controlled substances act.

Designer Drugs

Designer Drugs

Stimulant Agents Cocaine Amphetamines Decongestants Beta Stimulators Withdrawal States Cannabinoids

– JWH-018, JWH-073, JWH-200– CP-47,497,

Cannabicyclohexanol– HU-210

Designer Drugs

Stimulant AgentsMechanisms of Action - ?

Designer Drugs

Stimulant AgentsMechanisms of Action

Stimulant AgentsMechanisms of Action Central inhibition of

catecholamine reuptake– Epinephrine, norepinephrine

Peripheral stimulation of alpha & beta receptors

Additional effects (nuances)– Na channel / local anesthetic

(cocaine)– Serotonin reuptake inhibition

(MDMA) Designer Drugs

Designer Drugs

Stimulant Toxicity Clinical Management - ?

Designer Drugs

Stimulant ToxicityClinical Management

Central inhibition of catecholamine reuptake– Benzodiazepines (GABA receptor agonists)

0.1-0.2 mg/kg Diazepam IV (5-10 mg) 0.05 mg/kg Lorazepam or Midazolam IV

or 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 Droperidol

Designer Drugs

Stimulant ToxicityManagement

Peripheral stimulation of alpha & beta receptors– Benzodiazepines

(cardiac receptors)– Vasodilators;

phentolamine, nitroprusside

– Cardiac monitoring Additional effects

– Benzodiazepines– Hydration, Cooling,

Neuromuscular paralysis Designer Drugs

Spice Case A 20 year-old female

“crazy” Tachycardic,

hypertensive, warm, & wet – (P 140, BP 185/110)

Diazepam 5 mg IV X 2 Temp 104.4o

– Urine reddish brown– IV ½ NS with 2 amps

NaHCO3

Designer Drugs

Spice Case CT head negative Urine Tox negative Admitted ICU

– Continuous EEG monitoring

Awakens next morning– Admits binge of

“Spice”– Peak CPK 14,000– No renal failure– Discharged home

intact day #3Designer Drugs

Smoking ‘Bath Salts’ 26 y.o. male –

agitated & confused

3 day binge – Smoking

‘Bolivian Bath Salts’

Roomate found him face-down on floor Designer Drugs

26 Year Old Male Agitated & Confused Management?

Designer Drugs

Initial Management WA Poison

Center 1-800-222-

1222 1-800-709-

0911

Airway Breathing Circulation

– 80% of poisonings Disability/

Decontamination– 90% of poisonings

Exposure/Elimination– Antidotes– 100% of poisoningsDesigner Drugs

26 Year Old Male Agitated & Confused Agitated, responding to loud

verbal A – Open with intact gag reflex B - RR 28 / minute, clear lungs C - Tachycardic (Sinus - 130’s)

Hypertensive (160/100) D - No Seizure, Glucose 120 Decontamination? E – Elimination?

Designer Drugs

‘Bath Salts’ Case Agitated, responds to loud verbal

stimuli No trauma Pupils 6 mm P 130 BP 160/100 Diaphoretic & Hot

Designer Drugs

Physical ExaminationStimulant Syndrome Vital Signs Mental Status Pupils Mucus

membranes Respiratory Gastrointestina

l Skin

T, P, R, BP Seizures Dilated &

reactive Moist Rate, depth Motility Pink, warm,

moistDesigner Drugs

“Bath Salts” “White Ice, Ocean

Snow, Lunar Wave, Purple Wave, Ivory Wave, Ivory Soft, Vanilla Sky, Bliss”

$20 packets from convenience stores, truck stops & via Internet

Designer Drugs

“Bath Salts” - Compounds Very similar to amphetamines Side effects largely the same we

see with amphetamines in large dose– Jeffrey Baldwin, University of

Nebraska Medical Center Typically snorted, smoked, injected Can be mixed with water as a

beverage Designer Drugs

Snorting & Smoking Bath Salts

Designer Drugs

“Bath Salts” - Contents Mephedrone MDPV (3,4-

methylenedioxypyrovalerone)

Designer Drugs

Mephedrone - Europe Cathinone derivative Marketed as ‘plant

feeder’ ‘not for human consumption’

Potentially addictive & Increasingly popular legal

substitute for cocaine & ecstasy

Designer Drugs

MDPV – 3,4 methylendioxypyrovalerone

Epinephrine & Nor-epinephrine re-uptake inhibitor

Designer Drugs

MDPV – 3,4 methylendioxypyrovalerone

Epinephrine & Norepinephrine re-uptake 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

hrsDesigner Drugs

MDPV Toxicity -?

Designer Drugs

“Bath Salts” Toxicity 35 patients, Michigan ED’s 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

hours at hospital Tachycardia resolves

with IV benzos & fluids

Temp 104.1 Urine (+) benzos

only CK Peak 6500Designer Drugs

Cannabinoids & Bath Salts 2010 - 2011

Designer Drugs

Olives TD, et al. Bath salts: the ivory wave of trouble.West J Emerg Med. 2012 Feb;13(1):58-62.

“Bath Salts” - Banned DEA Temporary Schedule I (Oct

2011)– Up to 12 months for permanent

Louisiana, Florida, North Dakota, WA– New York, Kentucky, Mississippi -

Pending PC calls fell with Louisiana ban

– Now ordering by Internet – Shipping to Mississippi

Executive Health February 04, 2011

Designer Drugs

Stimulant Agents Cocaine Amphetamines Decongestants Beta Stimulators Withdrawal States Cannabinoids ‘Bath Salts’

– Mephedrone– MDPV

Designer Drugs

New “Rave” (2 C agents) 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-phenethylamine

Designer Drugs

2, 5, I-NBOMe DeathsErowid.org (Extracts)

March 2012 – Adult male South Australia – 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

ingestionDesigner Drugs 2011

2 Ci Blotter Paper

Designer Drugs

Designer Drugs

2 C-I

Designer Drugs

PhenethylaminesChemical Name Street Name

3,4,5-trimethoxy-phenethylamine

Mescaline

2C-E 2,5-dimethoxy-4-ethyl-phenethylamine

Europa

2C-B 2,5-dimethoxy-4-bromo-phenethylamine

Bees, Bromo, Bromo mescaline, Nexus, Spectrum, Toonies, Venus

2C-I 2,5-dimethoxy-4-iodo-phenethylamine

N-Bomb

2C-T7 2,5-dimethoxy-4-propylthio-phenethylamine

Blue Mystic, Vanilla Aroma

Designer Drugs

Phenethylamines Agonist/antagonist 5-HT receptor

– Hallucinations– Over-stimulation & agitation

(amphetamines) Multiple forms

– Tablets, capsules, powder for insufflation

Kinetics– Onset 20 min, peak 2 hrs, duration 6-

12 hrs Designer Drugs

Designer Drugs

Phenethylamines Clinical Effects

– Hallucinations, agitation, seizures– Hyperthermia, tachycardia, hypertension,

tachypnea– Extreme/rapid cycling emotions– Mydriasis, flushing, diaphoresis– Nausea, vomiting, – Facial dystonia (teeth grinding, grimacing)– Rhabdomyolysis

Designer Drugs

Phenethylamines (cont)

– Insufflation - immediate pain nasal mucosa

– 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 AgentsMechanisms of Action Central inhibition of

catecholamine reuptake– Epinephrine, norepinephrine

Peripheral stimulation of alpha & beta receptors

Additional effects (nuances)– Na channel / local anesthetic

(cocaine)– Serotonin reuptake inhibition

(MDMA) Designer Drugs

Poisoning Management

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 - Expanded, Urine Test (8756U)– Methamphetamine, Amphetamine, O-Desmethyltramadol – MDMA, MDEA, MDA, DOM– Mephedrone, MDPV, Pyrovalerone,, Ethylone, Flephedrone,

Buphedrone, 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 - Expanded, Urine (Forensic) Test (9562U)– AM-2201, JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-

210, JWH-250, & RCS-4 metabolites

Tox Update 2012

Stimulant Toxicity - Key Points Central & Peripheral catecholamine surge

– Characteristic clinical toxicological syndrome Specific agents

– Cocaine, amphetamines, decongestants, cannabinoids, Mephedrone, MDPV, phenethylamines

– Often unavailable for decontamination & detection

– Treat the patient, not the agent Importance - reduce severity of poisoning

(avoid complications)– Benzodiazepines & Hyperthermia preventionDesigner Drugs

“Spice” References– Gunderson EW, et al. "Spice" and "K2" herbal

highs: a case series and systematic review of the clinical effects and biopsychosocial implications of synthetic cannabinoid use in humans. Am J Addict. 2012 Jul-Aug;21(4):320-6.

– Simmons JR, et al. Intoxication from smoking "spice”. Ann Emerg Med. 2011 Feb;57(2):187-8.

– Vardakou I, et al. Spice drugs as a new trend: mode of action, identification & legislation. Toxicol Lett 2010 Sep 1;197(3):157-62.

– Schneir AB, et al. "Spice" Girls: Synthetic Cannabinoid Intoxication. J Emerg Med 2010 Dec 15.

Designer Drugs

“Bath Salts” - References

Designer Drugs

o Borek HA, et al. Hyperthermia and multiorgan failure after abuse of "bath salts" containing 3,4-methylenedioxypyrovalerone. Ann Emerg Med. 2012 Jul;60(1):103-5.

o Prosser JM, Nelson LS. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol. 2012 Mar;8(1):33-42.

o Murray BL, et al. Death following recreational use of designer drug "bath salts" containing 3,4-Methylenedioxypyrovalerone (MDPV). J Med Toxicol. 2012 Mar;8(1):69-75.

o 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.

o Emergency department visits after use of a drug sold as "bath salts"--Michigan, November 13, 2010-March 31, 2011. MMWR 2011 May 20;60(19):624-7.

o Psychonaut WebMapping Research Group, Mephedrone Report, Institute of Psychiatry, King's College London, London, UK (2009).

Update in Toxicology 2013 Goal

– Increase knowledge in management of the poisoned patient

Objectives– Describe manifestations &

management of the stimulant syndrome

– List new designer drugs, their mechanisms, & their sources

Designer Drugs

Update in Toxicology 2013 K2, Spice, Bath Salts,

& the New Designer Drugs

William Hurley, MD FACEP Harborview Medical

Center Washington Poison Center

– hurleyw@uw.edu– hurley@wapc.org– (800) 222-1222– (800) 709-0911