The new psychoactive substances: Toxicity and management

Transcription

1 The new psychoactive substances: Toxicity and management Bruno Mégarbane, MD, PhD Department of Medical and Toxicological Critical Care INSERM UMRS Paris-Diderot University Lariboisière Hospital, Paris, France bruno.megarbane@lrb.aphp.fr

2 Count of drug Top 20 most commonly reported drugs in the ED in Europe 1600 (n=8709 in 5529 presentations) EuroDEN, Clin Tox 2015

3 Classification of NPS stimulants according to DAT/SERT ratio 5-HT Dominant DA Dominant

4 1 Toxicity of synthetic cathinones N= 236 Adrenergic signs Encephalopathy signs Serotoninergic signs Organ dysfunction Spiller HA. Clin Tox 2011

5 Intoxications involving MDPV - the Swedish STRIDA project - Beck O. ClinTox 2015

6 Toxicity of aminoindanes, piperazines, and pipradrol derivatives - Structural similarities with MDMA and MDA - A serotonin-releasing agent producing empathogenic effects and acting as sedative, rather than generating stimulant action Expected effects: mild euphoria, empathy, increased mental clarity, sexual arousal, intensification of sensory experience, music appreciation, visual distortions, mood enhancement, sociability and loquacity Adverse effects: insomnia, nausea/vomiting, confusion and fatigue Serotonin syndrome = possible factor in fatalities Corkery JM. Hum. Psychopharmacol Clin Exp 2013

7 Cathinone-induced dependence liability Conditioned place preference The animal preferring to spend more time in the environment associated with the drug MEPH/methylone/MDPV produce more CPP than amphetamine MEPH-induced environmental CPP persists for at least 3 weeks Karlsson L. BCPT 2014 Self-administration paradigms Evaluation of drug reinforcing potential as predictor of addictive properties Acquisition with greater potency with MDPV than amphetamine Escalation of intake at higher rather than lower MDPV doses Watterson LR. Addict Biol 2012

8 2 Toxicity of synthetic cannabinoids First generation: Nausea/vomiting, Occasional seizures More recent generation: Seizures, Cardiotoxicity, Sympathomimetic syndrome Serotoninergic syndrome Cardiovascular events Stroke Hermanns-Clausen M. Addiction 2012

9 Ischemic stroke associated with the use of a synthetic cannabinoid (ADB-FUBINACA) Moeller S. Asian J Psychiatry 2016

10 Hemorrhagic stroke following synthetic cannabinoid use Rose DZ. Neurology 2015

11 Repeated thrombosis after synthetic cannabinoid use Raheemullah A. J Emerg Med 2016

12 Cannabinoids-induced AKI (N=16) Age: yrs - Intense nausea and flank or abdominal pain - Median peak creatinine: 6.6 mg/dl; proteinuria (N=8), casts (N=5), RBC in urine (N=8); increased cortical echogenicity (N=9/12) Biopsy (N=8): tubular injury (N=6); interstitial nephritis (N=3) Detection of fluorinated SCB (XLR-11) (N=4/6) All patients were hospitalized; one required dialysis; none died Tait RJ. Clin Tox 2016

13 Cannabinoid hyperemesis acute renal failure Risk factors: male, intractable vomiting, constant hot showers Habboushe J. Am J Emerg Med 2014

14 AK Karat Gold Foil Wrapper containing herbal products, recovered from a patient involved in the outbreak (12 Jul 2016, Brooklyn, New York)

15 Fatalities attributed to synthetic cannabinoids Type de spice Auto-mutilations (AM2201) Patton AL. J Forensic Sci 2013

16 3 Toxicity of the psychedelic hallucinogens N-Bome (Bromo-dragonfly) Psychedelic hallucinogen drug belonging to the phenylethylamine family 300 time more powerful than mescaline and 1/5 time than LSD Powerful 5-HT 2A, agonist with -agonist effects Wood DM. JMT 2009

17 Toxicity of methoxetamine (High-affinity selective NMDA-R antagonist) N=47 Hill SL. Emerg Med J 2014

18 4 The first count of fentanyl deaths in 2016: Up 540% in three years Drug overdoses killed ~ 64,000 people Fentanyl Heroin Prescription analgesics Cocaine Methamph Methadone New York Times 2017

19 Intoxications involving acrylfentanyl the Swedish STRIDA project - Efficiency of naloxone when used Helander A. Clin Tox 2017

20 Acute skin and hair symptoms followed by severe, delayed eye complications in subjects using the synthetic opioid MT-45 Widespread folliculitis and dermatitis Helander A. Br J Dermatol 2016

21 Management of NPS-poisoned patients Mainly in EMD > ICU Supportive care - Fluids - Sedation (BZD) if agitation, anticonvulsive if seizures - Oxygenation if respiratory failure - Catecholamines if circulatory failure - Intubation + MV if coma or life-threatening presentation - ECTR (hemodialysis): for electrolytic equilibration No role to enhance elimination Cyproheptadine (5HTR- 2A et 5HTR- 2C antagonist) to treat NPS-related serotonin syndrome + external cooling, muscle paralyzing agents. Dantrolene controversial Naloxone to reverse opioid NPS-related neuro-respiratory depression (Possible higher doses to avoid intubation)

22 Take home message 1- NPS toxicity as mainly amphetamine-like 2- Possible life-threatening presentation and organ failure 3- Importance of analytical identification 4- Supportive care Agitation Confusion Seizures Adrenergic Sd Serotoninergic Sd Organ failure Recreational context Negativity of the usual tox screening (opiates, cocaine, amphetamine, THC) - Suspect NPS intoxication - Call the Poison Center - Send a blood sample to a specialized Tox lab