amphetamine
Summary
Amphetamine is a sympathomimetic amine that increases release and blocks reuptake of catecholamines (dopamine, norepinephrine) in the CNS, producing stimulant effects. It is used therapeutically for ADHD and narcolepsy but has high abuse potential and can cause severe cardiovascular and psychiatric toxicity in overdose.
Detail
Mechanism: Amphetamine is a substrate-type releaser that enters presynaptic terminals via the dopamine transporter (DAT) and norepinephrine transporter (NET), is taken up into synaptic vesicles via VMAT2, and causes reverse transport of monoamines out of the neuron into the synapse (indirect sympathomimetic). It also inhibits monoamine oxidase (MAO) at high doses, further increasing synaptic catecholamine levels. Net effect: increased dopamine and norepinephrine in the synaptic cleft, leading to CNS stimulation, increased alertness, decreased appetite, and enhanced sympathetic tone.
Clinical uses: Attention-deficit/hyperactivity disorder (ADHD), narcolepsy, and historically obesity (appetite suppression). Common formulations include dextroamphetamine, mixed amphetamine salts (Adderall), and lisdexamfetamine (a prodrug with lower abuse potential due to slower conversion).
Acute toxicity/overdose: Presents with hypertension, tachycardia, arrhythmias, hyperthermia, mydriasis, diaphoresis, psychosis (paranoia, hallucinations), seizures, and potential for cardiovascular collapse. Chronic use can cause severe dental disease ("meth mouth" with methamphetamine), weight loss, cardiomyopathy, and psychosis resembling schizophrenia.
Withdrawal: Characterized by dysphoria, fatigue, increased appetite, hypersomnia ("crash") — contrasts with the autonomic hyperactivity seen in opioid or sedative withdrawal.
Drug interactions/testing: Amphetamines can cause false-positive urine drug screens with certain medications (e.g., bupropion, pseudoephedrine). Concurrent MAO inhibitor use risks hypertensive crisis due to excessive catecholamine release.
Pharmacokinetics: Well absorbed orally, metabolized hepatically, urinary excretion pH-dependent (acidic urine increases elimination).
Board relevance: Key to differentiate from cocaine (which blocks reuptake only, does not cause release) and from methylphenidate (similar mechanism, used for ADHD). Understand toxicity presentation and management (benzodiazepines for agitation/seizures, avoid beta-blockers alone due to unopposed alpha stimulation risk).
Sources
- Katzung's Basic and Clinical Pharmacology
- First Aid for the USMLE Step 1
- Goodman & Gilman's The Pharmacological Basis of Therapeutics
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.