title: The clinical toxicology of metamfetamine.
abstract: BACKGROUND
  Metamfetamine is a highly addictive amfetamine analog that acts primarily as a central nervous system (CNS) stimulant. The escalating abuse of this drug in recent years has lead to an increasing burden upon health care providers. An understanding of the drug's toxic effects and their medical treatment is therefore essential for the successful management of patients suffering this form of intoxication.
  
  
  OBJECTIVE
  The aim of this review is to summarize all main aspects of metamfetamine poisoning including epidemiology, mechanisms of toxicity, toxicokinetics, clinical features, diagnosis, and management.
  
  
  METHODS
  A summary of the literature on metamfetamine was compiled by systematically searching OVID MEDLINE and ISI Web of Science. Further information was obtained from book chapters, relevant news reports, and web material. Epidemiology. Following its use in the Second World War, metamfetamine gained popularity as an illicit drug in Japan and later the United States. Its manufacture and use has now spread to include East and South-East Asia, North America, Mexico, and Australasia, and its world-wide usage, when combined with amfetamine, exceeds that of all other drugs of abuse except cannabis. Mechanisms of toxicity. Metamfetamine acts principally by stimulating the enhanced release of catecholamines from sympathetic nerve terminals, particularly of dopamine in the mesolimbic, mesocortical, and nigrostriatal pathways. The consequent elevation of intra-synaptic monoamines results in an increased activation of central and peripheral α±- and β-adrenergic postsynaptic receptors. This can cause detrimental neuropsychological, cardiovascular, and other systemic effects, and, following long-term abuse, neuronal apoptosis and nerve terminal degeneration. Toxicokinetics. Metamfetamine is rapidly absorbed and well distributed throughout the body, with extensive distribution across high lipid content tissues such as the blood-brain barrier. In humans the major metabolic pathways are aromatic hydroxylation producing 4-hydroxymetamfetamine and N-demethylation to form amfetamine. Metamfetamine is excreted predominantly in the urine and to a lesser extent by sweating and fecal excretion, with reported terminal half-lives ranging from ∼5 to 30 h. Clinical features. The clinical effects of metamfetamine poisoning can vary widely, depending on dose, route, duration, and frequency of use. They are predominantly characteristic of an acute sympathomimetic toxidrome. Common features reported include tachycardia, hypertension, chest pain, various cardiac dysrhythmias, vasculitis, headache, cerebral hemorrhage, hyperthermia, tachypnea, and violent and aggressive behaviour. Management. Emergency stabilization of vital functions and supportive care is essential. Benzodiazepines alone may adequately relieve agitation, hypertension, tachycardia, psychosis, and seizure, though other specific therapies can also be required for sympathomimetic effects and their associated complications.
  
  
  CONCLUSIONS
  Metamfetamine may cause severe sympathomimetic effects in the intoxicated patient. However, with appropriate, symptom-directed supportive care, patients can be expected to make a full recovery.
authors.affiliation: National Poisons Centre, Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand. leo.schep@otago.ac.nz
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Schep
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Slaughter
authors.forename: D Michael G
authors.initials: DM
authors.lastname: Beasley
mesh_terms: D000697:Central Nervous System Stimulants / Q000506:poisoning*; D006801:Humans; D008694:Methamphetamine / Q000737:chemistry / Q000493:pharmacokinetics / Q000506:poisoning*; D011041:Poisoning / Q000175:diagnosis / Q000628:therapy
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine