the new psychoactive substances: toxicity and …€¦ · the new psychoactive substances: toxicity...
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The new psychoactive substances:Toxicity and management
Bruno Mégarbane, MD, PhD
Department of Medical and Toxicological Critical Care
INSERM UMRS 1144 - Paris-Diderot University
Lariboisière Hospital, Paris, France
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gTop 20 most commonly reported drugs in the ED in Europe
(n=8709 in 5529 presentations)
EuroDEN, Clin Tox 2015
Classification of NPS stimulants according to DAT/SERT ratio
5-HTDominant
DADominant
Toxicity of synthetic cathinones
N= 236
Adrenergic signs
Encephalopathy signs
Serotoninergic signs
Spiller HA. Clin Tox 2011
Organ dysfunction
1
Intoxications involving MDPV - the Swedish STRIDA project -
Beck O. ClinTox 2015
Corkery JM. Hum. Psychopharmacol Clin Exp 2013
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
- Structural similarities with MDMA and MDA
- A serotonin-releasing agent producing empathogenic effects
and acting as sedative, rather than generating stimulant action
Toxicity of aminoindanes, piperazines, and pipradrol derivatives
Conditioned place preference
The animal preferring to spend more time in the environment associated with the drug
Karlsson L. BCPT 2014
MEPH/methylone/MDPV produce more CPP than amphetamine
MEPH-induced environmental CPP persists for at least 3 weeks
Cathinone-induced dependence liability
Self-administration paradigms
Evaluation of drug reinforcing potential as predictor of addictive properties
Acquisition with greater potency with MDPV than amphetamineEscalation of intake at higher rather than lower MDPV doses
Watterson LR. Addict Biol 2012
Toxicity of
synthetic cannabinoids
Hermanns-Clausen M. Addiction 2012
First generation:
Nausea/vomiting,
Occasional seizures
More recent generation:
Seizures,
Cardiotoxicity,
Sympathomimetic syndrome
Serotoninergic syndrome
Cardiovascular events
Stroke
2
Ischemic stroke associated with the use of a synthetic cannabinoid (ADB-FUBINACA)
Moeller S. Asian J Psychiatry 2016
Rose DZ. Neurology 2015
Hemorrhagic stroke following synthetic cannabinoid use
Raheemullah A. J Emerg Med 2016
Repeated thrombosis after synthetic cannabinoid use
Age: 15 – 27 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
Cannabinoids-induced AKI (N=16)
Tait RJ. Clin Tox 2016
Cannabinoid hyperemesis acute renal failure
Habboushe J. Am J Emerg Med 2014
Risk factors: male, intractable vomiting, constant hot showers
AK-47 24 Karat Gold Foil Wrapper containing herbal products, recoveredfrom a patient involved in the outbreak(12 Jul 2016, Brooklyn, New York)
Auto-mutilationsType de spice
(AM2201) Patton AL. J Forensic Sci 2013
Fatalities attributed to synthetic cannabinoids
Psychedelic hallucinogen drug belonging to the phenylethylamine family
300 time more powerful than mescaline and 1/5 time than LSD
Powerful 5-HT2A, agonist with -agonist effects
Toxicity of the psychedelic hallucinogens
N-Bome (Bromo-dragonfly)
Wood DM. JMT 2009
3
Toxicity of methoxetamine
Hill SL. Emerg Med J 2014
N=47
(High-affinity selective NMDA-R antagonist)
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
4
Intoxications involving acrylfentanyl– the Swedish STRIDA project -
Helander A. Clin Tox 2017
Efficiency of naloxone when used
Widespread folliculitis and dermatitis
Helander A. Br J Dermatol 2016
Acute skin and hair symptoms followed by severe, delayed eye
complications in subjects using the
synthetic opioid MT-45
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 equilibrationNo 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)
Take home message
AgitationConfusionSeizures
Adrenergic SdSerotoninergic Sd
Organ failure
1- NPS toxicity as mainly amphetamine-like
2- Possible life-threatening presentation and organ failure
3- Importance of analytical identification
4- Supportive care
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