BLACK BOX WARNING
- high potential for abuse and dependence (Schedule II)
- misuse may cause sudden death and serious cardiovascular adverse events
amphetamine (mixed amphetamine salts)
Brand: Adderall, Adderall XR, Mydayis
⚠ BBW Prototype: methylphenidate
Drug Class: CNS stimulant
Drug Family: CNS stimulant
Subclass: amphetamine
Organ Systems: cns
Mechanism of Action
Enters presynaptic neurons and displaces dopamine and norepinephrine from vesicles (via VMAT2), causing reversal of DAT and NET to expel monoamines into the synapse — a fundamentally different mechanism from methylphenidate (which blocks reuptake without reverse transport). Net result is massive increase in synaptic dopamine and norepinephrine.
VMAT2 (vesicular monoamine transporter)DAT (dopamine transporter)NET (norepinephrine transporter)
Indications
- attention deficit hyperactivity disorder (ADHD)
- narcolepsy
Contraindications
- concurrent or recent MAOI use
- hyperthyroidism
- advanced arteriosclerosis
- moderate to severe hypertension
- symptomatic cardiovascular disease
Adverse Effects
Common
- appetite suppression
- insomnia
- weight loss
- headache
- dry mouth
- palpitations
- irritability
Serious
- hypertension
- tachyarrhythmias
- sudden cardiac death (rare; pre-existing cardiac abnormality risk)
- psychiatric symptoms (psychosis, mania, aggression)
- growth suppression in children
Pharmacokinetics (ADME)
| Absorption | well absorbed orally; food has minimal effect on total absorption but delays peak for XR |
| Distribution | protein binding ~15-40%; Vd ~3-5 L/kg; crosses BBB extensively |
| Metabolism | CYP2D6 to active 4-hydroxyamphetamine; also direct oxidation; urinary pH significantly affects renal excretion |
| Excretion | renal; acidic urine increases elimination (t½ shorter); alkaline urine decreases elimination (t½ longer) |
| Half-life | 10-13 hours (d-amphetamine); 13-14 hours (l-amphetamine) |
| Onset | 30-60 minutes |
| Peak | 3 hours (IR); 7 hours (XR) |
| Duration | 4-6 hours (IR); 8-12 hours (XR) |
| Protein Binding | 15-40% |
| Vd | 3-5 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| MAOIs | hypertensive crisis and serotonin syndrome | contraindicated |
| urinary alkalinizers (sodium bicarbonate) | decrease amphetamine excretion; increase levels and duration | moderate |
| urinary acidifiers (vitamin C, ammonium chloride) | increase amphetamine excretion; may precipitate withdrawal | moderate |
Nursing Considerations
- Obtain baseline cardiovascular assessment (BP, HR, weight, height in children); perform ECG if family history of cardiac disease or arrhythmia before initiating.
- Monitor growth parameters (height and weight) every 6 months in children; drug holidays during summer may partially mitigate growth suppression.
- Assess for signs of psychiatric adverse effects (hallucinations, aggression, mania) at follow-up visits; discontinue if new psychiatric symptoms emerge.
- Schedule II controlled substance requiring special prescribing requirements; document diversion screening, prescription monitoring program (PDMP) check, and drug supply reconciliation at each visit.
Clinical Pearls
- The 'paradoxical calming' of amphetamines in ADHD is not paradoxical at the neurobiological level; increasing prefrontal cortical dopamine and norepinephrine strengthens top-down inhibitory control, reducing hyperactivity and impulsivity.
- Urine pH significantly affects amphetamine half-life: alkalinizing urine (taking antacids) extends the half-life to 16-30 hours, while acidifying it shortens the half-life to 7-14 hours — dietary and supplement habits can alter clinical response.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.