Pharmacology, Toxicology and Addiction MedicineTier 1Disease (DEADMAN)

Acute and chronic effects, including overdose, from the use of - amphetamines

Description

Amphetamines/methamphetamine - sympathomimetic stimulant class
Acute: euphoria, alertness, sympathomimetic toxidrome at high dose (see toxidromes-sympathomimetic) - agitation, psychosis, hyperthermia
Chronic: dependence, stereotyped/repetitive behaviour, dental decay ("meth mouth"), cardiomyopathy, persisting psychosis

Epidemiology

Methamphetamine ("ice") use and related harms have risen sharply in Australia over the past decade
Associated with high rates of ED presentation for acute agitation/psychosis and with intimate partner/community violence

Aetiopathogenesis

inc release + blocked reuptake of dopamine, noradrenaline, serotonin at the synapse
Chronic use -> dopaminergic neurotoxicity -> contributes to amphetamine-induced psychosis, which can persist or recur even after abstinence
Sympathomimetic overdrive -> hyperthermia, rhabdomyolysis, cardiomyopathy with chronic high-dose use

Diagnosis

Acute toxicity - clinical (see toxidromes-sympathomimetic)
Chronic use - clinical history, urine drug screen; methamphetamine-induced psychosis can be clinically indistinguishable from primary schizophrenia during an episode - distinguish by rapid resolution with abstinence (days-weeks) vs persistence
ECG (arrhythmia risk), CK (rhabdomyolysis), echo if cardiomyopathy suspected with chronic heavy use

Management

Acute

Benzodiazepines for agitation/psychosis; antipsychotics as adjunct for persistent psychotic symptoms
Active cooling, IV fluids for hyperthermia/rhabdomyolysis

Chronic dependence

Psychosocial interventions (CBT, contingency management) - no approved pharmacotherapy for methamphetamine dependence in Australia (unlike opioid/nicotine substitution)
Manage psychiatric comorbidity and cardiomyopathy on their own merits

Associations

Psychosis, depression, anxiety
Cardiomyopathy, stroke (haemorrhagic and ischaemic)
Blood-borne virus risk with injecting use

Natural history & complications

Acute psychosis usually resolves within days to weeks of abstinence, but recurrent psychosis with re-use or later stressors is common
Cardiomyopathy may improve with sustained abstinence but can be irreversible with prolonged heavy use

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