7/25/2015 49th Annual Meeting Disclosure I do not have a vested interest in or affiliation with any corporate organization offering financial Novel Psychoactive Substances: support or grant monies for this continuing education “Coming soon to an Emergency Department Near You” activity, or any affiliation with an organization whose philosophy could potentially bias my presentation Patrick Aaronson, PharmD, DABAT [email protected] Clinical Pharmacist - Emergency Medicine UF Health - Jacksonville Clinical Assistant Professor, College of Pharmacy OWNING CHANGE: Taking Charge of Your Profession Objectives: Pharmacist Objectives: Technician 1. Describe emerging drugs of abuse 1. List the new emerging drugs of abuse 2. Examine mechanisms of action and clinical effects 2. Describe the pharmacological and clinical effects of for the newer drugs of abuse new drugs of abuse 3. Explore treatment options and supportive care for patients presenting with acute illicit drug intoxication/overdose Common References for Discussion Topics Novel Psychoactive Substances (NPS) NBOMe’s Excited Delirium Methoxetamine and Methoxphenidine Poisindex® 1 7/25/2015 Novel Psychoactive Substances (NPS) “New Things” Clandestine labs (precursor materials) Rebranding Manufacturing capacity (batch size) Different formulations Delivery Vehicles (spiked consumer products) New Combos Analogs Marketing: (websites / search engines) Drug distributors: drug cartels / Gangs Drug distributors: websites www.lycaeum.org www.erowid.org www.dancesafe.org Adapted from: Peredy, TR. “Emerging Drugs of Abuse: Finding the Adapted from: Peredy, TR. “Emerging Drugs of Abuse: Finding the Reality” North American Congress of Clinical Toxicology, New Reality” Orleans, LA. 20 Oct. 2014 North American Congress of Clinical Toxicology, New Pictures to the right: http://www.businessinsider.com/what-is-synthetic-marijuana- Orleans, LA. 20 Oct. 2014 2015-5?op=1 Novel Psychoactive Substances (NPS) Emerging Drugs of Abuse European Epidemiology Emergency Department Visits Poison Centers Media Surveys www.monitoringthefuture.org DEA Emerging Trends www.drugabuse.gov/drugs-abuse/emerging-trends Pooled urine? (United Kingdom) Sewage-based epidemiology QJM. 2013 Feb;106(2):147-52 Clin Toxicol (Phila). 2014 Mar;52(3):160-5 Adapted from: Wood, DM. “NPS What is the Harm” Drug Test Anal. 2015 Feb 6 North American Congress of Clinical Toxicology, New Orleans, LA. 20 Oct. 2014 Hallucinogens NBOMe: characteristics Blotting paper, powder, liquid, IV MDMA 2CB 25I NBOMe 1 Route: Most common: Oral / Sublingual (6-12 hrs) “N-Bomb” Injection, vaginally, rectally, smoked “Smiles” Detected: “Solaris” Liquid chromatography with mass spectrometry 2 “Holland Film” n = 582 (42% drug source was website) “Boom” “Pandora” 1: Biomed Res Int. 2014;2014:734749 NBOMe 1: Neuropharmacology 2014; 77:200-207 2: J Psychopharmacol. 2014 Aug;28(8):780-8 Biomed Res Int. 2014;2014:734749 Right Picture: https://www.erowid.org/chemicals/nbome/nbome_article1.shtml 2 7/25/2015 NBOMe: Proposed Mechanism NBOMe Clinical Effects 2013 – 2015 Case Series / Reports Highly potent 5HT 2A receptor agonist Duration of Clinical effects: 10 hrs – 13 days Serotonergic tone Moderate to Serious Outcomes: n ~ 50 Most Common Agitation Aggression Tachycardia Hyperpyrexia Hallucinogenic Hallucinations Hypertensive Delirium (Excited Delirium) Seizures Rhabdomyolysis ↑ CK Mydriasis gran mal Renal Injury Alpha-adrenergic agonist, Inhibit reuptake of monoamines (DA, NE, 5HT) Coma Metabolic Amnesia Deaths (9) acidosis Sympathomimetic Agitation and Physical Aggression Least Common Leukocytosis Acute lung Lower Extremity Serotonin failure rigidity Syndrome Hyperthermia, metabolic acidosis, rhabdomyolysis Clin Toxicol (Phila). 2013 Mar;51(3):174-7, Clin Toxicol (Phila). 2013 Jul;51(6):487-92, Drug Test Anal. 2014 Jul-Aug;6(7-8):764-9, Forensic Sci Int. 2014 Jan;234:e14-20, Am J Forensic Med Pathol. 2014 Mar;35(1):20-5, J Psychopharmacol. 2014 Aug;28(8):780-8., Med Klin Intensivmed Notfmed. 2014 May;109(4):271-5., Clin Toxicol (Phila). 2014 Jun;52(5):561-5, Drug Clin Toxicol (Phila). 2014 Jun;52(5):561-5 Chem Toxicol. 2015 Jan;38(1):113-9, Am J Emerg Med. 2014 Nov;32(11):1444.e3-5, Biomed Res Int. 2014;2014:734749, J Addict Dis. 2014;33(3):196-201, J Med Toxicol. 2014 Nov J Med Toxicol. 2014 Nov 12 12, Psychosomatics. 2015 Mar-Apr;56(2):129-39, Forensic Sci Int. 2015 Jun;251:e1-8. Eur J Pharmacol 2007 559:132–137 NBOMe Exposures Florida 2015 Excited delirium 4 cases Delirium with agitation Ages 14 – 17 y/o Violence, hyperactivity, and hyperthermia Clinical Effects Agitation / irritable Result: Sudden and unexpected cardiopulmonary Hallucinations / delusions arrest Seizures Fever / hyperthermia Pathophysiology: abnormal dopamine processing Hypertension / tachycardia Unable to compensate for rapid increase in dopamine Rhabdomyolysis Renal Failure levels J Med Toxicol. 2013 9:172-178 J Emerg Med 2012 43:897–905 FPICN Query Builder Arch Gen Psychiatry 1998 55:793–799 Ann Neurol 1996 40:428-430 Phencyclidine and Ketamine: Epidemiology U.S. Dissociatives Ketamine1,2 Health Care Facility Moderate to Severe Outcomes - Ketamine 2012 150 67 2013 147 68 - Phencyclidine - Methoxetamine Phencyclidine1,2 Health Care Facility Moderate to Severe Outcomes - Methoxphenidine 2012 348 183 2013 282 140 1ClinicalToxicology 2013; 51:949 -1229 2ClinicalToxicology 2014; 52:1032 - 1283 3 7/25/2015 Arycyclohexylamines (Dissociatives) Clinical Manifestations: Dissociatives Pathophysiology Common Findings 2 Nystagmus , blank stare (diplopia) “Dissociate" the somatosensory cortex from higher centers 1 Lack of response to external stimuli (Dissociated) NMDA receptor antagonists psychosis, analgesia, anesthesia Hypertension 3 Inhibit biogenic amine reuptake sympathomimetic Violent/agitated/bizarre behavior Concentrations Stimulation of sigma receptors coma Hallucinations / delusions Drug 4 Higher concentrations associated with death Rhabdomyolysis renal failure Nicotinic Large Doses coma Increasing Cholinergic Opioid 1Adv Exp Med Biol. 1990;268:27-33 2Anesth Analg. 1966;45:29-40 Ann Emerg Med. 1981;10:237-242 3Synapse. 1991;8:289-300 4Brain Res. 1978;152:176-182 Clinical Manifestations: Neuropsychiatric Dissociatives Hallmark of PCP – delusion of “superhuman strength” Ketamine Methoxetamine Invulnerability Jumping MXE Fighting large crowds or police Mexxy Self mutilation MKet Ketamine Arch Intern Med 1992; 152:859-860 Methoxetamine Methoxetamine Methoxetamine Clinical Effects Characteristics Ketamine analog (Dissociative) 2011 – 2015 Case Series / Reports Moderate to Severe Outcomes: (n ~ 15) Slower onset / longer duration than ketamine Most Common Dissociative Hallucinations Catatonic Rotary NMDA receptor antagonist, Serotonin agonist, Dopamine Psychosis Nystagmus reuptake inhibition Agitation Mydriasis Tachycardia / Stupor Hypertensive Route: Oral, Insufflation, IM, IV, Rectal Cerebellar Amnesia Deaths (4) Detected: ataxia Coma Reparatory Hyperthermia Rhabdomyolysis Liquid chromatography Failure With mass spectrometry Least Common Acute Renal and ↑ Creatinine Hyponatremia Seizures Liver failure Kinase FPICN Query Builder, Clin Toxicol (Phila). 2011 Nov;49(9):874-5., Eur J Clin Pharmacol. 2012 May;68(5):853-6, Ann Emerg Med. 2012 Jul;60(1):97-9, Clin Toxicol (Phila). 2012 Jun;50(5):438-40, Med Hypotheses. 2012 Oct;79(4):504-7. , J Anal Toxicol. 2013 Jan-Feb;37(1):43-6, Emerg Med J. 2014 Jan;31(1):45-7. , Neurosci Ther. 2013 Jun;19(6):454-60 , Picture to the right: Przegl Lek. 2013;70(8):671-3., Ned Tijdschr Geneeskd. 2014;158, J Anal Toxicol. 2014 Sep;38(7):410-5. Int J Occup Med Environ Health. 2014 Aug;27(4):683-90, J Forensic Sci. 2015 Jan;60 Suppl 1:S264-8., philadelphia.cbslocal.com/2014/01/17/customs-officials- seize-dangerous-drug-at-philadelphia-ups-facility CNS Neurosci Ther. 2013 Jun;19(6):454-60 Clin Toxicol (Phila). 2011 Nov;49(9):874-5. 4 7/25/2015 Methoxphenidine / Diphenidine Dissociatives Characteristics Phencyclidine Methoxphenidine Route: nasal, IV, smoked (vaporized), rectal Oral (“bombed”) in ∼50–150 mg doses MXP Onset delayed ~ 1 hr (risk for overdosing) Phencyclidine Duration: 3 – 7 hrs PCP Detected: Liquid chromatography with mass spectrometry Methoxphenidine Clin Toxicol (Phila). 2015 Jun;53(5):446-53 Methoxphenidine Clinical Effects Legal High? 2014 Case Series Federal Schedule State Schedule n = 14 (diphenidine), n = 3 (methoxphenidine) 25I NBOMe Temporary Schedule I FL, GA, LA, VA Hallucinations Disoriented Anxiety Dissociation 25B NBOMe Coma (n=3) Agitated 20% 25C NBOMe Mydriasis Nystagmus Tachycardia Hypertension Horizontal and Vertical Methoxetamine Not Federally Regulated Al, AZ, FL, IN, LA, MN, ND, OH, VA, UT Urinary Retention Muscle Rigidity Prolonged activated partial Methoxphenidine Not Federally Regulated Not Regulated thromboplastin time (n=2) Clin Toxicol (Phila). 2015 Jun;53(5):446-53 J Anal Toxicol. 2015 May;39(4):287-93 Fed Regist. 2014 Mar 7;79(45):12938-43 Clin Toxicol (Phila). 2014 Dec;52(10):1288-91 Treatment Primarily supportive Management: Clinical Pearls Hallucinogens and Dissociatives Think about adulterants Quiet supportive environment Hydration, sedation, quiet environment (minimal stimuli) Agitation (“bad trip”) “talking the patient down” Benzodiazepines www.emsworld.com/article/10324064/ 5 7/25/2015 Treatment Treatment: Excited delirium Benzodiazepines: Seizures, Agitation Rapid sedation, IV fluids, decrease hyperthermia Caution