Sympathomimetic Toxidrome

The sympathomimetic toxidrome results from excessive stimulation of the sympathetic nervous system through direct receptor agonism (phenylephrine, epinephrine), indirect catecholamine release (amphetamines release stored norepinephrine and dopamine from presynaptic vesicles), reuptake inhibition (cocaine blocks norepinephrine and dopamine transporters), or MAO inhibition (preventing catecholamine degradation). The clinical presentation reflects widespread alpha-1, beta-1, and beta-2 adrenergic activation plus dopaminergic stimulation. Alpha-1 activation: peripheral vasoconstriction (hypertension), mydriasis, urinary retention, diaphoresis. Beta-1 activation: increased heart rate, contractility, and conduction velocity (tachycardia, hypertension, arrhythmias). Beta-2 activation: bronchodilation, tremor. Dopaminergic activation: euphoria, psychomotor agitation, psychosis. Common causative agents: cocaine (dopamine/NE reuptake inhibitor + sodium channel blocker — unique risk of QRS widening and ventricular arrhythmias), amphetamines/methamphetamine (release + reuptake inhibition of catecholamines), MDMA/ecstasy (serotonin + catecholamine release — overlap with serotonin syndrome), synthetic cathinones (bath salts), pseudoephedrine/ephedrine, caffeine overdose. Complications: hyperthermia (potentially fatal — from agitation, seizures, vasoconstriction impairing heat dissipation), rhabdomyolysis (from agitation and hyperthermia), seizures, intracranial hemorrhage (severe hypertension), aortic dissection, acute coronary syndrome (coronary vasospasm + thrombosis, especially cocaine), and cardiac arrhythmias.