Designer Drugs: New ways of achieving old highs
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1 Designer Drugs: New ways of achieving old highs Jen Stephani, MD Oregon Poison Center/OHSU PeaceHealth Southwest WA Medical Center Department of Emergency Medicine Objectives Discuss social & legal evolution of designer drugs Discuss emerging stimulant drugs of abuse that may lead to severe agitation & aggression Understand the importance of early recognition and resuscitation in synthetic stimulant abuse Discuss emerging synthetic opioids being abused and management The culprits Stimulants Synthetic cannabinoids Synthetic cathinones Substituted phenethylamines Opioids Kratom Loperamide Fentanyl/Carfentanyl Flakka Salvia 1
2 The Problem with Synthetic Drugs Clandestinely manufactured to mimic effects of cocaine, meth and marijuana Product mislabeling & inconsistency Changing ingredients over time Safety unknown Dependence Regulation of synthetic drugs 1986: Controlled Substances Analogue Enforcement Act requires intent that a drug analog be manufactured or sold "for human consumption" before becoming prosecutable. Analogue Act, cont. A controlled substance analogue is a substance which is intended for human consumption and is structurally or pharmacologically substantially similar to or is represented as being similar to a Schedule I or II substance and is not an approved medication in the United States 2
3 Common designer stimulants Synthetic Drug Class Mimics effect of: Examples Cannabinoids Marijuana K2 Spice Phenyethylamines Phencyclidines or Arylcyclohexamines Stimulants & hallucinogens PCP Tryptamines Hallucinogens AMT DMT Piperazines Hallucinogens BZP MDMA/amphetamines Cathinones 2C series NBOMe Ketamine Methoxetamine 4-Me-PCP Synthetic cannabinoids Synthetic Cannabinoids Functionally similar but structurally dissimilar to THC Act directly on CB-1 & CB-2 receptors Varying degrees of affinities for receptors and pharmacologic profiles 3
4 Synthetic Cannabinoids Not your parent s pot Psychological Neurological Cardiovascular Metabolic GI Renal Autonomic Anxiety, aggression, agitation, confusion, dysphoria, paranoia, hallucinations Seizures Tachycardia, hypertension, chest pain Hypokalemia, hyperglycemia Nausea, vomiting Acute kidney injury Hyperthermia, mydriasis Synthetic Cannabinoids Phenethylamines 4
5 Phenethylamine Cathinone Methamphetamine 2C-I 25I-NBOMe The Godfather of Ecstasy MDMA, it was beginning to be apparent, could be all things to all people. 2C drugs (2-CI) Club drug/young males Similar to amphetamines, created by multiple substitutions/additions to make more hallucinogenic Common substituent in ecstasy (polypharmacy) Unknown pharmacology, but most work at serotonin receptors +/- other receptors Many are Schedule 1 5
6 2C drugs Clinical effects 2C-B: diffuse cerebral vasculopathy likely from vasospasm 2C-I: recurrent seizures & serotonin syndrome with hyperthermia Deaths have been reported Psychiatric CNS Cardiovascular Gastrointestinal Other Hallucinations, psychosis, confusion, depression Dizziness, HA, seizures, cerebral vasospasm Tachycardia, hypertension, cardiac arrest Nausea, vomiting, diarrhea Body aches, serotonin syndrome 25-NBOMe N-bomb, I-Beam, 25I, 25C, 25B Linked to at least 19 deaths (ages 15-29) Mar 2012 Aug 2013 No human use before 2010 Sold as LSD as liquid on blotter paper Agitation, aggression, self-harming behavior Tachycardia, HTN, tachypnea, hyperthermia Metabolic acidosis, rhabdo, kidney injury, seizures, and death Piperazines Fully synthetic Substituted as ecstasy; polydrug abuse Benzylpiperazine (BZP) most common Clinically, BZP produces effects similar to meth Combo BZP/TFMPP mimics actions of MDMA Insomnia, anxiety, HA, N/V, tremor, diaphoresis, confusion, hallucinations, paranoia, seizures, QT prolongation, hyponatremia, serotonin syndrome, hyperthermia, rhabdo, renal failure 6
7 Tryptamines Psilocybin & Psilocin are naturally occurring tryptamine compounds in magic mushrooms Psilocybe caerulescens Tryptamines Already hallucinogenic but let s make it even better!!! Adding methoxy groups increases hallucinogenic properties Foxy methoxy (5-methoxy-N,Ndiisopropyltryptamine) Cathinones 7
8 What are cathinones? Khat Cathinone Methamphetamine Street Names for Bath Salts Bath salts, plant food, jewelry cleaner Arctic Blast Cloud 9 Lady Bubbles Snow Day Aromatherapy Cloud 10 Lunar Wave Snow Leopard Bayou Ivory Flower Cotton Cloud Mr. Nice Tranquility Bliss Dynamite Mystic Vanilla Sky Bloom Dynamite Plus Ocean Snow Whack Blue Magic Euphoria Pure Ivory White Blue Silk Gold Rush Pure White White Girls Bolivian Hurricane Purple Rain White Horse Bonsai Winter Boost Ivory Fresh Red Dove White Lightning C Original Ivory Wave Route 69 Wicked X Charge Plus Ivory Wave Ultra Scarface Zoom Synthetic Cathinones Readily available White clumpy powder or pill form Most commonly insufflated or ingested 8
9 Actual substances in bath salts Methcathinone Mephedrone Methylenedioxypyrovalerone (MDPV) Methylone Butylone Brephedrone Pyovalerone Dimethylecathinone Ethcathinone Ethylone Methedrone Naphyrone 3-Fluoromethcathinon 4-Fluoromethcathinone Pyrrolidinovalerophenone MDPPP Molly or is it? Flakka (alpha-pvp) Also known as gravel Synthetic cathinone Outbreak in 2016, mostly in SE US Associated with cases of bizarre behavior/agitation/aggression 9
10 Cathinones clinical effects CNS Cardiovascular Gastrointestinal Renal Metabolic Ophthalmologic Other AMS, seizures, headache, tremors, nystagmus Tachycardia, hypertension, palpitations, chest pain, myocardial infarction, dysrhythmias Abdominal pain, nausea/vomiting Acute kidney injury Hyponatremia, acidosis Mydriasis, blurred vision Hyperthermia, diaphoresis, bruxism, epistaxis, rhabdomyolysis Synthetic cathinones 10
11 Salvia Naturally-occurring hallucinogen Found in Salvia divinorum Magic mint, Mystic sage, Sally D Smoked, ingested as tea, or chewing the plant leaves Stimulates serotonin and kappa opioid receptors Salvia Perceptual distortions, pseudohallucinations, altered sense of self and environment Adverse effects generally mild: confusion, disorientation, hallucinations, dizziness, flushing Rare cases of acute psychosis & paranoia Rapid in onset & quickly dissipate within 30 minutes Management of stimulant toxicity 11
12 ABC s General Management Initial assessment Vitals, cardiac monitoring, pulse oximetry IV access Blood glucose Control agitation Control temperature Control seizures Male, mean age 36 Excited Delirium Clinical Features Psychostimulant abuse +/- psychiatric disease Agitation, paranoia Hyperaggressive, combative behavior with ongoing struggle despite futility Impervious to pain Nudity and bizarre behavior Pathophysiology Unregulated dopamine & serotonin levels Leads to catecholamine surge & metabolic acidosis Acidosis + sudden catecholamine surge cardiac arrest Deaths often after violent struggle Fighting, resisting and fleeing can be lifethreatening by worsening the acidosis Early & rapid sedation is CRITICAL 12
13 Route Dosing (mg) Onset (min) Duration (min) Midazolam IM IV Lorazepam IM IV Diazepam IM IV Haloperidol IM IV Droperidol IM IV Ziprasidone IM Olanzapine IM hrs Ketamine IM 4-5 mg/kg IV 2 mg/kg ABC s General Management Control agitation Control temperature Cold fluids External cooling Intravascular catheters Temp >40 Likely will be intubated & paralyzed ABC s General Management Control agitation Control temperature Control seizures Benzos, benzos, more benzos Check sodium 13
14 Opioids Beyond prescription opioids and heroin Kratom Naturally occurring substance in Mitragyna spp. Used for hallucinogenic effects and self-treatment of opioid withdrawal Smoked, ingested as tea Duration of effect 1 hour (dose dependent) Mitragynine is active substance Becoming Schedule 1? Kratom More likely to present with opioid toxicity or withdrawal Seizures Particular form (Krypton) may be associated with more severe toxicity & seizures (tramadol metabolite added) Not reported if naloxone reverses kratom (opioid-like) toxicity; reasonable to try Supportive management 14
15 Loperamide Mu opioid agonist with minimal central CNS effects Used to get high or to treat opioid withdrawal symptoms Case series in 2014 of cardiac conduction abnormalities Seen with doses of 100 mg Loperamide Overdose QTc prolongation leading to Torsades QRS prolongation/brugada-like ECG Fentanyl & Derivatives Fentanyl 100x more potent than morphine Derivatives even more potent Becoming popular on the street Fentanyl patch abuse 15
16 Fentanyl & Derivatives Management of Fentanyl & Derivatives in Overdose ABC s Naloxone don t stop at 2mg! Serial dosing if no response: 0.4 mg 2 mg 4 mg 6 mg 10 mg Take-Away Points There are too many new drugs to know them all; Recognize the toxidrome management is the same Be able to recognize severe sympathomimetic effects and recognize the importance of early sedation Recognize that standard doses of naloxone may not be enough to treat synthetic opioid toxicity 16
17 Questions? 17
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