Dextroamphetamine
Dextroamphetamine
Generic Name
Dextroamphetamine
Mechanism
- Neurotransmitter Release Agonist – ↑ synaptic dopamine (DA) and norepinephrine (NE) by reversing the dopamine transporter (DAT) and norepinephrine transporter (NET), leading to increased synaptic monoamine concentrations.
- Inhibition of Monoamine Oxidase (MAO) – weak inhibition of MAO‑A and MAO‑B, prolonging dopamine/NE action.
- Stimulation of α1‑adrenergic & β‑adrenergic Receptors – contributes to vasoconstriction, ↑ blood pressure, and tachycardia.
- Central Nervous System (CNS) Stimulation – enhances cortical arousal, improves attention, and suppresses fatigue in narcolepsy.
Pharmacokinetics
| Parameter | Details |
| Absorption | Oral bioavailability ~ 70–85 % (decreases with high‑fat meals). |
| Tmax | 1–4 h (IR); 6–9 h (XR preparations). |
| Distribution | Volume of distribution ~ 3–4 L/kg; crosses blood‑brain barrier; >90 % protein‑bound. |
| Metabolism | Hepatic: N‑dealkylation, hydroxylation, glucuronidation. Minor CYP450 involvement (CYP2D6, CYP3A4). |
| Excretion | Renal (≈70 %) as unchanged drug and metabolites; half‑life: 10–12 h (IR), 12–20 h (XR). |
| Drug Interactions |
• MAO‑I ↑ risk of serotonin syndrome and neuro‑toxicity. • CYP2D6 inhibitors (e.g., fluoxetine) can prolong half‑life. • α1‑agonists and β‑agonists potentiate cardiovascular effects. |
Indications
- Attention‑Deficit/Hyperactivity Disorder (ADHD) in children, adolescents, and adults.
- Narcolepsy – maintenance therapy for excessive daytime sleepiness.
- Adjunctive Depression – used off‑label in some treatment‑resistant depressive disorders (low‑dose).
- Severe Obesity (FDA: dextroamphetamine, not mixed with lisdexamfetamine) – short‑term adjunctive therapy.
- Adjunct for Chronic Pain/Anxiety – considered in selected practice settings under specialist supervision.
Contraindications
| Category | Key Points |
| Contraindications |
• Pregnancy (Category D); • Severe cardiovascular disease (e.g., uncontrolled hypertension, tachyarrhythmia, ischemic heart disease); • Narrow‑angle glaucoma; • Severe agitation or psychosis; • Known hypersensitivity. |
| Warnings |
• High abuse potential – schedule II controlled substance. • Cardiovascular toxicity (arrhythmias, acute hypertension); • Neuropsychiatric adverse events (mania, psychosis). • Growth suppression in pediatric patients; • Concomitant MAO inhibitors (serotonin syndrome). |
| Precautions |
• Use cautiously in seizure disorders (may lower seizure threshold). • Avoid abrupt discontinuation to prevent rebound insomnia or irritability. |
Dosing
| Population | Starting Dose | Titration | Maintenance Dose | Formulation |
| Children (≤12 yr) | 0.3 mg/kg/day (max 10 mg) | Increase 2–3 mg every 3–7 days | 5–10 mg twice daily | IR |
| Adolescents (13–17 yr) | 5 mg once or twice daily | 5 mg increments | 20–30 mg/day | XR (e.g., Adderall XR) |
| Adults | 5 mg once daily | 5 mg increments | 10–40 mg/day | IR / XR |
| Narcolepsy | 5 mg TID | 5 mg increments | 15–30 mg/day | IR |
| Severe Obesity | 5 mg once daily | 5 mg increments | 20 mg/day | IR |
• Administration: Oral tablet; XR release delayed for 3–4 h. Do not crush, chew, or split XR tablets.
• Missed Dose: Take at the next scheduled time; skip if >2 h after planned.
• Drug Holidays: Use only on weekends or as clinically indicated to reduce abuse potential.
Adverse Effects
| Category | Representative Symptoms |
| Common (≤10 %) |
• Dry mouth; • Insomnia; • Appetite suppression; • Weight loss; • Headache; • Palpitations; • Nausea; • Dizziness |
| Serious (≤1 %) |
• Hypertension / tachycardia; • Supraventricular arrhythmias; • Psychosis/mania; • Severe agitation; • Rebound withdrawal; • Sudden unexplained death (rare, usually in predisposed patients) |
Monitoring
- Vital Signs: BP, HR at baseline, 30 min post‑dose, and during titration.
- Growth Metrics: Height/weight in pediatric patients quarterly.
- Psychosis Screening: Baseline psychiatric assessment; follow‑up every 3–6 months.
- Cardiac Evaluation: ECG for patients >35 yr or with cardiovascular risk factors.
- Laboratory: CBC, CMP, lipid panel annually.
- Drug Abuse Surveillance: Urine drug screening in high‑risk populations.
Clinical Pearls
- Extended‑Release vs. Immediate‑Release – XR formulations decrease abuse potential and improve adherence by reducing peak plasma concentrations.
- Growth Suppression – Document pediatric growth trajectories; consider dose reductions or drug holidays after 6 months if significant deceleration occurs.
- MAO‑I Interaction Alert – A 2‑week washout is mandatory when switching from an MAO inhibitor to dextroamphetamine to avoid serotonin syndrome.
- Weight‑Loss Adjunct – Use only short‑term (≤12 weeks) due to high relapse and potential for abuse; monitor for mood changes.
- Perioperative Considerations – Discontinue before anesthesia to avoid intraoperative hypertension; resume when clinically indicated.
- Pregnancy & Lactation – Category D; avoid unless benefits outweigh risks; minimal excretion in breastmilk—avoid breastfeeding.
- Non‑Intake Behaviors – In elderly or comorbid patients, the risk of cardiovascular events outweighs benefit – consider alternative ADHD therapies.
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• *All dosing instructions and clinical practice recommendations reflect current formulary information as of 2024. Always corroborate with institutional protocols and updated guidelines.*