1. Update in Toxicology 2013
K2, Spice, Bath Salts, & the New Designer Drugs
William Hurley, MD FACEP
Harborview Medical Center
Washington Poison Center
(800)
(800)

2. Update in Toxicology 2013 Goal Objectives
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

3. Tox Update 2012

4. Designer Drugs

5. Designer Drugs

6. 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?
Designer Drugs

7. 20 Year Old Female Anxious & Agitated
Initial Evaluation ?
Designer Drugs

8. 20 Year Old Female Anxious & Agitated
Mental Status
A –
B –
C –
D –
E –
Designer Drugs

9. 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
Designer Drugs

10. Initial Management Airway Breathing Circulation
80% of poisonings
Disability/Decontamination
90% of poisonings
Exposure/Elimination
Antidotes
100% of poisonings
WA Poison Center
Designer Drugs

11. 20 Year Old Female Anxious & Agitated
Agitated, responding to loud verbal
A – Open with intact gag reflex
B - RR / minute, clear lungs
C - Tachycardic (Sinus - 130’s)
Hypertensive (180/110)
D - No Seizure, Glucose 108
Decontamination?
E – Elimination?
Designer Drugs

12. Poisoning Management Focused History Focused Physical Examination
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

13. Toxicologic Syndromes
Asphyxiant
Cholinergic
Anticholinergic
Cyclic Antidepressant
Opiod
Sedative
Stimulant
Hallucinogenic
Serotonergic
Hepatotoxic
Heavy Metal
Irritant gas
Caustic
Salicylates
Toxic Alcohols
Hydrocarbons
Calcium antagonists
Designer Drugs

14. Poisoning Management Physical Examination – Toxicologic Syndrome
Designer Drugs

15. 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, moisture
Designer Drugs

16. Poisoning Case A 20 year-old female “crazy”
Tachycardic, hypertensive, warm, & wet
(P 130, BP 185/110)
Synthetic marijuana?
Designer Drugs

17. Poisoning Case A 20 year-old female “crazy”
Tachycardic, hypertensive, warm, & wet
(P 130, BP 185/110)
Synthetic marijuana?
Toxicologic Syndrome?
Designer Drugs

18. Physical Examination Stimulant Syndrome
Vital Signs
Mental Status
Pupils
Mucus membranes
Respiratory
Gastrointestinal
Skin
T, P, R, BP
Seizures
Dilated & reactive
Moist
Rate, depth
Motility
Pink, warm, moist
Designer Drugs

19. Spice Case
Roomate produces packets of incense purchased at a local “head shop.”
Designer Drugs

20. Designer Drugs

21. Spice Case A 20 year-old female “crazy” Begins screaming & struggling
Attempting IV
Has 3 minute seizure
Management?
Designer Drugs

22. Stimulant Agents - ?
Designer Drugs

23. Stimulant Agents Cocaine Amphetamines Decongestants Beta Stimulators
Methamphetamine, Ecstasy, methylphenidate, phentermine
Decongestants
Ephedrine, Pseudo-ephedrine
Beta Stimulators
Albuterol, caffeine, theophylline
Withdrawal States
EtOH, benzodizepine, GHB
Designer Drugs

24. Designer Drugs

25. Cannabinoids

26. 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

27. 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

28. Plant & Herbal Blends Marketed as incense Desire for ‘legal high’
Ability to avoid detection on drugs-of-abuse testing (THC)
Designer Drugs

29. What’s up with the Eye?
Designer Drugs

30. 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

31. Cannabinoids Heterogeneous structured compounds
Agonize endogenous cannabinoid receptors
Include phytocannabinoids derived from Cannabis sativa (delta 9-THC)
Endogenous cannabinoids
Synthetics
Designer Drugs

32. 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

33. Cannabinoids Signs & Symptoms
Tachycardia
Hypertension
Hyperthermia
Anxiety
Seizures
Paranoia & hallucinations
Designer Drugs

34. European Experience Within weeks of regulatory control
Non-prohibited cannabinoids found in products
Structures heterogeneous
No THC rxn
Designer Drugs

35. Synthetic Cannabinoids 2010
JWH – 250
13%
JWH – 73
11%
U.S. DEA, Office of Diversion Control

36. 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

37. Synthetic Cannabinoids 2011
JWH – 250
12%
AM-2201
29%
JWH – 210 9%
JWH-18
14%
JWH-122
12%
U.S. DEA, Office of Diversion Control

38. 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

39. Designer Drugs

40. Stimulant Agents Cocaine Amphetamines Decongestants Beta Stimulators
Withdrawal States
Cannabinoids
JWH-018, JWH-073, JWH-200
CP-47,497, Cannabicyclohexanol
HU-210
Designer Drugs

41. Stimulant Agents Mechanisms of Action - ?
Designer Drugs

42. Stimulant Agents Mechanisms of Action

43. Stimulant Agents Mechanisms 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

44. Designer Drugs

45. Stimulant Toxicity Clinical Management - ?
Designer Drugs

46. Stimulant Toxicity Clinical Management
Central inhibition of catecholamine reuptake
Benzodiazepines (GABA receptor agonists)
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

47. Stimulant Toxicity Management
Peripheral stimulation of alpha & beta receptors
Benzodiazepines (cardiac receptors)
Vasodilators; phentolamine, nitroprusside
Cardiac monitoring
Additional effects
Benzodiazepines
Hydration, Cooling, Neuromuscular paralysis
Designer Drugs

48. 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

49. 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 #3
Designer Drugs

50. 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

51. 26 Year Old Male Agitated & Confused
Management?
Designer Drugs

52. Initial Management Airway Breathing Circulation
80% of poisonings
Disability/Decontamination
90% of poisonings
Exposure/Elimination
Antidotes
100% of poisonings
WA Poison Center
Designer Drugs

53. 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

54. ‘Bath Salts’ Case Agitated, responds to loud verbal stimuli No trauma
Pupils 6 mm
P 130 BP 160/100
Diaphoretic & Hot
Designer Drugs

55. Physical Examination Stimulant Syndrome
Vital Signs
Mental Status
Pupils
Mucus membranes
Respiratory
Gastrointestinal
Skin
T, P, R, BP
Seizures
Dilated & reactive
Moist
Rate, depth
Motility
Pink, warm, moist
Designer Drugs

56. “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

57. “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

58. Snorting & Smoking Bath Salts
Designer Drugs

59. “Bath Salts” - Contents
Mephedrone
MDPV (3,4-methylenedioxypyrovalerone)
Designer Drugs

60. Mephedrone - Europe Cathinone derivative
Marketed as ‘plant feeder’ ‘not for human consumption’
Potentially addictive &
Increasingly popular legal substitute for cocaine & ecstasy
Designer Drugs

61. MDPV – 3,4 methylendioxypyrovalerone
Epinephrine & Nor-epinephrine re-uptake inhibitor
Designer Drugs

62. 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 hrs
Designer Drugs

63. MDPV Toxicity -?
Designer Drugs

64. “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

65. ‘Bath Salts’ Case Agitated for 18 hours at hospital
Tachycardia resolves with IV benzos & fluids
Temp 104.1
Urine (+) benzos only
CK Peak 6500
Designer Drugs

66. Cannabinoids & Bath Salts 2010 - 2011
Olives TD, et al. Bath salts: the ivory wave of trouble.
West J Emerg Med Feb;13(1):58-62.
Designer Drugs

67. “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

68. Stimulant Agents Cocaine Amphetamines Decongestants Beta Stimulators
Withdrawal States
Cannabinoids
‘Bath Salts’
Mephedrone
MDPV
Designer Drugs

69. 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.)
2,5-dimethoxy-4-ethyl-phenethylamine
Designer Drugs

70. 2, 5, I-NBOMe Deaths Erowid.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 yo female, NC
25i pills, died >12 hours after ingestion
Designer Drugs 2011

71. 2 Ci Blotter Paper
Designer Drugs

72. Designer Drugs

73. 2 C-I
Designer Drugs

74. Phenethylamines Mescaline Europa N-Bomb 2C-E 2C-B 2C-I 2C-T7
Chemical 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

75. Phenethylamines Agonist/antagonist 5-HT receptor Multiple forms
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

76. Designer Drugs

77. 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

78. Phenethylamines (cont)
Insufflation - immediate pain nasal mucosa
Law enforcement officers
Phenethylamine laboratories
Mucous membrane & respiratory symptoms
Designer Drugs

79. Phenethylamines Legal control “Bad trips” ?alleviated by SSRIs?
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

80. Stimulant Agents Cocaine Amphetamines Decongestants Beta Stimulators
Withdrawal States
Cannabinoids
‘Bath Salts’
Phenethylamines
2 CE & 2 CI
Designer Drugs

81. Stimulant Agents Mechanisms 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

82. Poisoning Management Focused History Focused Physical Examination
ABCDE – Poison Center ( )
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

83. 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

84. 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 prevention
Designer Drugs

85. “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 Jul-Aug;21(4):320-6.
Simmons JR, et al. Intoxication from smoking "spice”. Ann Emerg Med 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):
Schneir AB, et al. "Spice" Girls: Synthetic Cannabinoid Intoxication. J Emerg Med Dec 15.
Designer Drugs

86. “Bath Salts” - References
Borek HA, et al. Hyperthermia and multiorgan failure after abuse of "bath salts" containing 3,4-methylenedioxypyrovalerone. Ann Emerg Med Jul;60(1):103-5.
Prosser JM, Nelson LS. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol Mar;8(1):33-42.
Murray BL, et al. Death following recreational use of designer drug "bath salts" containing 3,4-Methylenedioxypyrovalerone (MDPV). J Med Toxicol 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 Mar;38(2):
Emergency department visits after use of a drug sold as "bath salts"--Michigan, November 13, 2010-March 31, MMWR 2011 May 20;60(19):624-7.
Psychonaut WebMapping Research Group, Mephedrone Report, Institute of Psychiatry, King's College London, London, UK (2009).
Designer Drugs

87. Update in Toxicology 2013 Goal Objectives
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

88. Update in Toxicology 2013
K2, Spice, Bath Salts, & the New Designer Drugs
William Hurley, MD FACEP
Harborview Medical Center
Washington Poison Center
(800)
(800)