Acute toxic effects of ‘Ecstasy’ (MDMA) and related compounds: overview of pathophysiology and clinical management

Abstract

Since the late 1980s 'Ecstasy' (3,4-methylenedioxymethamphetamine, MDMA) has become established as a popular recreational drug in western Europe. The UK National Criminal Intelligence Service estimates that 0.5-2 million tablets are consumed weekly in Britain. It has been reported that 4.5% of young adults (15-34 yr) in the UK have used MDMA in the previous 12 months. Clinically important toxic effects have been reported, including fatalities. While the phenomenon of hyperpyrexia and multi-organ failure is now relatively well known, other serious effects have become apparent more recently. Patients with acute MDMA toxicity may present to doctors working in Anaesthesia, Intensive Care and Emergency Medicine. A broad knowledge of these pathologies and their treatment is necessary for anyone working in an acute medical speciality. An overview of MDMA pharmacology and acute toxicity will be given followed by a plan for clinical management.

Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction

“…Pathological hyperthermia is one of the most dangerous symptoms of acute MDMA intoxication and can cause serious health complications, including severe neurological impairment, rhabdomyolysis, organ failure, and even lethality (Kalant, 2001;Gowing et al, 2002;Hall and Henry, 2006). Although relatively rare, this response is unpredictable and strongly potentiated under common environmental and social conditions of recreational MDMA use.…”

“…Robust hyperthermia is the most dangerous symptom of acute MDMA intoxication, often leading to serious health complications and even death (Kalant, 2001;Gowing et al, 2002;Hall and Henry, 2006). The temperature effects of MDMA are relatively modest when the drug is administered to humans or animals under standard laboratory conditions (Mechan et al, 2002;Freedman et al, 2005;Liechti, 2014), but are strongly potentiated under conditions of high activity, social interaction, and warm ambient temperature (Gordon et al, 1991;Brown and Kiyatkin, 2004;Parrott, 2012).…”

Kreislaufstillstand unter besonderen Umständen: Elektrolytstörungen, Vergiftungen, Ertrinken, Unterkühlung, Hitzekrankheit, Asthma, Anaphylaxie, Herzchirurgie, Trauma, Schwangerschaft, Stromunfall

“…Andere Medikamente wie "3,4-methylenedioxymethamphetamine" (MDMA, "Ecstasy") und Amphetamine können einen MH-ähnlichen Zustand hervorrufen, dessen Behandlung von der Verwendung von Dantrolen profitieren dürfte [292]. [296].…”

Êxtase (MDMA): efeitos farmacológicos e tóxicos, mecanismo de ação e abordagem clínica

“…Muitos desses efeitos são explicados pelas ações euforizantes da droga, somados aos ambientes com música repetitiva e grande quantidade de pessoas. Além disso, os neurotransmissores 5-HT e a DA liberados pelo MDMA estão envolvidos no controle central da termorregulação, conservando e gerando calor 66 .…”

“…Cada ampola contém 20 mg de dantroleno puro com 3 g de manitol e hidróxido de sódio, resultando em um pH final de 9,5, após a adição de 60 mL de água estéril. O manitol presente no dantroleno ajuda na manutenção da diurese e, somado à alcalinização da urina, são adequados para proteger o usuário do MDMA da insuficiência renal provocada pela mioglobinúria 66 .…”