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Current drugs of abuse

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J Laes
Medical Toxicology

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Current drugs of abuse

  1. 1. JoAn Laes, MD Medical Toxicology Fellow HealthPartners Institute for Graduate Medical Education September 2013 Current Drugs of Abuse
  2. 2. › Diagnosis, management and prevention of poisoning and other adverse health effects due to medications, occupational and environmental toxins, and biological agents Medical Toxicology
  3. 3. › Division of Emergency Medicine at Regions Hospital › The Regions Toxicology Service is actively engaged in patient consultations throughout the Twin Cities as well as education and research – Bedside consultation at Regions Hospital – Medical direction at Hennepin Regional Poison Center Medical Toxicology Fellowship HealthPartners Institute for Graduate Medical Education
  4. 4. › Current Drugs of Abuse and Epidemiology – Focus on emerging synthetic drugs › Pharmacology and clinical effects › Pre-Hospital Management of Drug Overdose – Synthetic drug abuse diagnosis and management – EKG in toxicology – Naloxone administration Outline
  5. 5. › Recent dramatic increase in unregulated synthetic psychoactive substances – Wide availability due to › Loopholes in legality › Easy to obtain from headshops or internet › Promoted by discussion boards/self study on internet › Many can cause life threating health effects – Unknown ingredients – No consistency in manufacturing Synthetic Drugs
  6. 6. › Dopamine and Norepinephrine: Sympathomimetic effects › Serotonin: Hallucinogenic effects › There is overlap between the neurotransmitter effects and many drugs affect several neurotransmitters Neurotransmission
  7. 7. Sympathomimetic Effects
  8. 8. Hallucinogenic Effects
  9. 9. Synthetic Cannabinoid
  10. 10. › Synthetic Cannabinoids – synthesized chemicals placed on dried plant material and smoked – HU210 first synthesized in 1988 › potency more than 100x THC – ‘CP’ compounds › Developed as potential analgesic in 1980 by a pharmaceutical company – ‘JWH’ compounds › Developed for research › JWH-018 Synthetic Cannabinoids
  11. 11. › Functionally (NOT structurally) similar to tetrahydrocannabinol (THC) Synthetic Cannabinoid
  12. 12. › Other effects – Tachycardia – Postural hypotension Clinical Effects: Cannabinoids
  13. 13. › Faster onset, quicker elimination › Additional mechanism of action – Serotoninergic effects › Nausea/vomiting › Hypertension › Tachycardia › Seizures Synthetic Cannabinoids Effects
  14. 14. › Hennepin Regional Poison Center – 9/1/2012 – 9/1/2013 › Received calls about 90 exposures to THC homologues Minnesota Trends
  15. 15. › Consumers becoming more experienced with use › Clinicians becoming more experienced with effects of synthetic drugs › Legislation has decreased availability and use Why the decline in calls?
  16. 16. › Federal DEA Scheduled – AKB48 (APINACA) and 5F- AKB48 (5F-APINACA) – CP 47,497 and homologues – HU-210 – JWH-018 – JWH-073 – UR-144 and XLR11 Legal i. Naphthoylindoles, 1-Pentyl-3-(1-naphthoyl)indole (JWH-018 and AM-678); 1-Butul-3-(1- naphthoyl)indole (JWH-073);1-Pentyl-3-(4-methoxy-1-naphthoyl)indole (JWH- 081); 1-[2-(4-morpholinyl)ethyl]-3-(1-naphthoyl)indole (JWH-200) (ii) Napthylmethylindoles, 1-Pentyl-1H-indol-3-yl-(1-naphthyl)methane (JWH-175);1-Pentyl-1H-indol-3-yl- (4-methyl-1-naphthyl)methan (JWH-184). (iii) Naphthoylpyrroles, (5-(2-fluorophenyl)-1-pentylpyrrol-3-yl)-naphthalen-1-ylmethanone (JWH- 307). (iv) Naphthylmethylindenes, E-1-[1-(1-naphthalenylmethylene)-1H-inden-3-yl]pentane (JWH-176). (v) Phenylacetylindoles, :1-(2-cyclohexylethyl)-3-(2-methoxyphenylacetyl)indole (RCS-8); 1-pentyl-3-(2- methoxyphenylacetyl)indole (JWH-250);1-pentyl-3-(2- methylphenylacetyl)indole (JWH-251); 1-pentyl-3-(2- chlorophenylacetyl)indole (JWH-203). (vi) Cyclohexylphenols, 5-(1,1-dimethylheptyl)-2-[(1R,3S)-3-hydroxycyclohexyl]-phenol (CP 47,497); 5- (1,1-dimethyloctyl)-2-[(1R,3S)-3-hydroxycyclohexyl]-phenol (Cannabicyclohexanol or CP 47,497 C8 homologue) (vii) Benzoylindoles,. 1-Pentyl-3-(4-methoxybenzoyl)indole (RCS-4); 1-(5-fluoropentyl)-3-(2- iodobenzoyl)indole (AM-694); (4-methoxyphenyl-[2-methyl-1-(2-(4- morpholinyl)ethyl)indol-3-yl]methanone (WIN 48,098 or Pravadoline). (viii) Others specifically named: (6aR,10aR)-9-(hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl) - 6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol (HU-210);(6aS,10aS)-9- (hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl) -6a,7,10,10a- tetrahydrobenzo[c]chromen-1-ol (Dexanabinol or HU-211); 2,3-dihydro-5- methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de] -1,4-benzoxazin-6-yl-1- naphthalenylmethanone (WIN 55,212-2). Minnesota Statute
  17. 17. Phenethylamines
  18. 18. › Backbone molecular structure Phenethylamines
  19. 19. › Amphetamine, methamphetamine, 3,4-methylenedioxy- methamphetamine (MDMA), mescaline “Original” Phenethylamines
  20. 20. › Substitutions on backbone structure – Structural variation alters spectrum of activity, potency and effects › “Hallucinogenic” versus “Stimulant” properties “New” Phenethylamines 2C-I 25I-NBOMe
  21. 21. › Neurotransmitters – 5-HT (Serotonin) receptor agonists – Norepinephrine and dopamine Phenethylamines
  22. 22. – Cardiovascular › tachycardia, hypertension, palpitations, chest pain – Autonomic › Diaphoresis, hyperthermia, hyper-reflexia, clonus – Psychiatric › aggression , agitation, anxiety, Phenethylamines Clinical Presentation – Neurological › psychosis, hallucinations , seizures – Muscular › tremors, muscle hyperactivity, hyperthermia, Gastrointestinal – Gastrointestinal › Abdominal pain, nausea and vomiting, diarrhea
  23. 23. › Review of 17 calls regarding exposures to “Hallucinogenic Amphetamines” – Tachycardia : 80% › ~110-130bpm – Hallucinations: 50% – Seizure: 25% – Elevated CK: 25% › 300-900 – Benzodiazepines given : 60% › Lorazepam 2mg – Mydriasis: 25% – Hyperthermia: 10% › 101-103F Hennepin Regional Poison Center
  24. 24. Hennepin Regional Poison center 20 teenagers from a Minnesota suburb were on a “Party Bus” and were partying with 25-I • One teenager seemed to have taken more than his party-mates • Had two seizures and EMS was called • Intubated and sedated and admitted to intensive care unit • 5/1/13-9/19/13 • 5 calls about exposure to 25-I
  25. 25. › Male patient being seen in southern Minnesota, reportedly ingested LSD 2 hours prior to call to poison center – The hit was on a piece of Paper he dissolved under his tongue › Symptoms – agitation, dilated pupils, hr 110 › Treatment – agitation improved with 2mg lorazepam › Follow up – Patient reports the drug was 25-NBOMe 25I-NBOMe
  26. 26. › “purer” form of MDMA – May contain other synthetic stimulants › 2013:Hennepin Regional Poison Center 11 calls about Molly – Poison Center also is seeing a resurgence in Ecstasy › 2013 more than double the calls than in 2012
  27. 27. Ecstasydata.org
  28. 28. › Two teenagers partying on the beach – Reported drinking liquid “Molly” – Family member called EMS after noting one of the teenagers to be hallucinating, shaking, and flushed – EMS › Shaking, rigidity, pupils 8mm and sluggish › Muttering nonsensically and agitated – Hospital › 16 mg lorazepam – Became more altered but still tremulous and rigid › Intubated – Temp increased to 106.4, HR 200 › Benzodiazepine drip and external cooling initiated › Extubated hospital day 2 – No permanent sequelae Tales from St.Paul
  29. 29. › “Failed” pharmaceuticals – Potential antidepressant › Similar effect as amphetamines and MDMA – Dopamine, norepinephrine, serotonin – Frequently sold as ecstasy Piperazines
  30. 30. › Phencyclidine derivatives – 3-methoxyeticyclidine (3-MeO-PCE) – 4-MeO-PCP › Europe 2011 – Minnesota Regional Poison Center › PCP – 9/2011-9/2013 › 62 exposures Phencyclidine (PCP) and ketamine derivatives (Arylcyclohexylamines)
  31. 31. › Methoxetamine – First reported 2011 – Very similar effects as ketamine Ketamine Derivatives 0 2 10 2011 2012 2013 Hennepin regional Poison Center Methoxetamine Exposures Methoxetamine
  32. 32. › 1,3-Dimethylamine (DMAA) – Also called: methylhexanamine or geranium extract) – Uses › Recreational party drug › Dietary supplements – Jack3d › FDA received 86 adverse event reports thought to be related to DMAA – Adverse events: depression, anxiety, vomiting, loss of consciousness, chest pain, death Ketamine and Derivatives
  33. 33. Ketamine and PCP Effects › Affects Several neurotransmitters – NMDA, Opioid, Norepinephrine, Serotonin › Clinical Effects – Dissociative – Alteration of pain perception – Potential stimulation of the cardiovascular system
  34. 34. Tryptamines
  35. 35. Synthetic Tryptamines
  36. 36. › Euphoria › Time distortion › Hallucination, Religious experience › Gi: nausea and vomiting › Neuro: Seizures – Risk of serotonin syndrome Tryptamine Clinical Effects
  37. 37. › 9/2012-9/2013 – 4 exposures › Foxy methoxy › DMT › 4-ACO-DMT Hennepin Regional Poison Center › Life in Suburbia – 2 teenagers bought 4-ACO- DMT off internet › Snorted 10 lines › Paranoia, tremulous, hallucin ations › Emergency Department – Hr 95, BP 120/70, T 98.6 – Mental status: mildly altered
  38. 38. › Management of a patient you suspect has had a toxic ingestion Now…
  39. 39. › Sympathetic/Autonomic – Agitation, increased motor activity, tachycardia, hypertension › Hyperthermia, rhabdomyolysis, acidosis › Cardiovascular – Arrhythmia › Usually sinus tachycardia – Acute coronary syndrome, aortic dissection, intracranial hemorrhage › Neurological and Psychiatric – Seizures – Psychosis, hallucinations Medical Complications of Synthetic Drugs
  40. 40. › Benzodiazepines, benzodiazepines, benzodiazepines – Decrease catecholamine excess › Could consider vasodilators › Phentolamine (alpha-antagonist) › Nitroglycerin › Avoid artificial modulation of heart rate – Beta blockers – Calcium channel blockers – Anti-arrhythmics › Lidocaine is potential option however Treatment: Sympathetic Activation and Cardiovascular
  41. 41. › Benzodiazepines, benzodiazepines, benzodiazepines › Other agents – Neuroleptics › Example: holperidol (Haldol), Droperidol, Olanzapine (Zyprexa) – may paradoxically worsen symptoms – No randomized placebo studies comparing benzodiazepines to neuroleptics in phenethylamine intoxication – Avoid if patient has qt prolongation – Ketamine › Benefit: rapid onset, lack of respiratory depression › Risks: laryngospasm, stimulatory cardiovascular effects resulting in increased tachycardia and hypertension Treatment: Neurologic and Psychiatric Symptoms
  42. 42. › Fluid Resuscitation › Reduction of Hyperthermia – External cooling- ice packs – Reduction of muscle activity with sedation – Severe: intubate, paralyze, internal cooling – Do not recommend › Antipyretics – lower the hypothalamic set point – don’t decrease catecholamine excess Treatment: Hyper-metabolic state
  43. 43. Cardiovascular Toxicology Principles
  44. 44. › QTc>500 ms is associated with a 2- to 3-fold higher risk for TdP Prolonged QT interval
  45. 45. Torsades des Pointes
  46. 46. › If QTc>500ms – Administer 2 grams magnesium sulfate › stabilizes cardiac membranes › Corrects hypomagnesemia › If torsades de pointes occurs – Address correctable factors › Give more magnesium, consider potassium – Do not administer qt prolonging antiarrhythmics › Example: Amiodarone Prolonged QTc Management
  47. 47. › Increased Adrenergic tone – Sympathomimetics › Myocardial Sensitization – Halogenated hydrocarbons › Dust-off › Altered repolarization/conduction abnormalities – Sodium channel blockade › Tricyclic antidepressants › Cocaine › Diphenhydramine › Antidysrhythmics Ventricular Tachyarrhythmias
  48. 48. › If QRS>100msec – Sodium Bicarbonate 1-2 meq/kg › ~2-3 amps for average male – Use caution with anti-arrhythmics › Especially class 1a (procainamide) and 1c (flecainide), beta blockers, amiodarone – Sodium channel blockers: prolong the qrs › Class 1b may be acceptable – Lidocaine Management of Prolonged QRS
  49. 49. › Wide variation in recommended dosing – Poisin-dex: .4-2mg – Goldfrank Toxicology: .04mg-> .4mg->2mg->10mg › Reasons for variability – Amount needed depends on amount of receptors occupied by opioid › 1mg naloxone occupy 50% receptors › low dose may prolong time to improvement of ventilation – Precipitation of acute withdrawal in chronic users › .4mg – Half life of naloxone 60-90 minutes › Re-narcotized if discharged early
  50. 50. › Route – Studies conclude that intramuscular, subcutaneous, intranasal and nebulized naloxone viable alternatives if no intravenous access but note potential erratic absorption › May affect time to onset and total dose received › Viable alternatives if no intravenous access Naloxone
  51. 51. › National Survey of Drug Use and Health, 2012 report › American Association of Poison Control Centers › United Nations Office on Drugs and Crime › Emerging Drugs of Abuse Presentation, Katie Adams, MSE (2013) › New and Emerging Drugs of Abuse, Greg Janis, Med Tox (2012) Select References
  52. 52. › Dean, Be Vang, et al. "2C or not 2C: phenethylamine designer drug review."Journal of Medical Toxicology (2013): 1-7. › Seely, Kathryn A., et al. "Spice drugs are more than harmless herbal blends: A review of the pharmacology and toxicology of synthetic cannabinoids." Progress in Neuro- Psychopharmacology and Biological Psychiatry 39.2 (2012): 234-243. › Stellpflug, Samuel J., et al. "2-(4-Iodo-2, 5-dimethoxyphenyl)- N-[(2-methoxyphenyl) methyl] ethanamine (25I-NBOMe): Clinical Case with Unique Confirmatory Testing." Journal of Medical Toxicology (2013): 1-6. Selected References
  53. 53. › and Questions? Thank You

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