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Update in Toxicology 2013

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  1. 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

  2. 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

  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 1-800-222-1222 Designer Drugs

  10. 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 poisonings Initial Management Designer Drugs

  11. 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

  12. 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

  13. Asphyxiant Cholinergic Anticholinergic Cyclic Antidepressant Opiod Sedative Stimulant Hallucinogenic Serotonergic Hepatotoxic Heavy Metal Irritant gas Caustic Salicylates Toxic Alcohols Hydrocarbons Calcium antagonists Toxicologic Syndromes 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. Vital Signs Mental Status Pupils Mucus membranes Respiratory Gastrointestinal Skin T, P, R, BP Seizures Dilated & reactive Moist Rate, depth Motility Pink, warm, moist Physical ExaminationStimulant Syndrome 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 • 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. CannabinoidsSigns & 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 AM-2201 29% JWH – 250 12% 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 AgentsMechanisms of Action - ? Designer Drugs

  42. Stimulant AgentsMechanisms of Action

  43. 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

  44. Designer Drugs

  45. Stimulant Toxicity Clinical Management - ? Designer Drugs

  46. 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

  47. 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

  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