Download - Update in Toxicology 2013
Update in Toxicology 2013 K2, Spice, Bath Salts,
& the New Designer Drugs
William Hurley, MD FACEP Harborview Medical
Center Washington Poison Center
– [email protected]– [email protected]– (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
– [email protected]– [email protected]– (800) 222-1222– (800) 709-0911