Generic Name

Metoclopramide

Mechanism

Metoclopramide is a dopamine D2 receptor antagonist that also blocks 5‑hydroxytryptamine 3 (5‑HT3) receptors in the gastrointestinal tract.
• Gastro‑intestinal (GI) prokinetic effect: Disinhibition of acetylcholine release enhances lower esophageal sphincter tone, accelerates gastric emptying, and promotes intestinal motility.
• Central anti‑emetic effect: Blocks dopamine and serotonin receptors in the chemoreceptor trigger zone (CTZ) and the vomiting center, reducing nausea and vomiting.
• Peripheral anti‑emetic effect: Inhibits vagal afferents in the gut, diminishing reflex‑mediated emesis.

Pharmacokinetics

• Absorption: Rapid, oral bioavailability ∼30 % (≈70 % for IV).
• Distribution: Highly protein‑bound (~89 %); crosses the blood–brain barrier → risk of CNS side effects.
• Metabolism: Hepatically glucuronidated; minimal role of CYP enzymes.
• Elimination: Renal excretion; terminal half‑life 5–9 h (IV) and 3–7 h (oral).
• Special Populations: Dose adjustment in severe renal impairment (CrCl < 20 mL/min). No significant accumulation with short courses.

Indications

• Acute and chronic nausea & vomiting (post‑operative, chemotherapy, radiotherapy).
• Gastroparesis in diabetic or idiopathic patients.
• Upper GI motility disorders (e.g., dyspepsia with delayed gastric emptying).
• Pre‑operative anti‑emetic prophylaxis (≤ 24 h prior).
• Facilitates oral intake in patients with impaired GI motility.

Contraindications

• Absolute: Known hypersensitivity to metoclopramide; active CNS disorders (tardive dyskinesia, Parkinson’s disease).
• Relative: Seizure disorder, severe hepatic/renal disease, pregnancy (class D, but may be used when benefit outweighs risk).
• Warnings:
• Neuropsychiatric: Extrapyramidal symptoms (EPS), tardive dyskinesia; risk increases after ≥ 4 weeks of daily use.
• Cardiac: QTc prolongation (rare).
• Metabolic: Hypoglycemia risk in diabetics; monitor blood glucose.
• Hepatic: Hepatotoxicity rare but reported.

Dosing

• Duration: Short‑term ( 4 weeks to minimize EPS.

Adverse Effects

• Common
• Somnolence, fatigue, dizziness
• Headache, edema (especially lower extremities)
• Diarrhea or constipation (rare)
• Serious
• Extrapyramidal symptoms: acute dystonia, parkinsonism, akathisia
• Tardive dyskinesia (especially with chronic use)
• Severe hypotension (rare with IV)
• Neuroleptic malignant syndrome (extremely rare)
• Hepatotoxicity (transaminase elevation)
• Severe hypoglycemia in diabetics

Monitoring

• Neurologic: Watch for signs of EPS; schedule regular movement‑assessment exams after > 4 weeks therapy.
• Metabolic: Blood glucose monitoring in diabetic patients; assess for hypoglycemia.
• Renal function: Serum creatinine/CrCl at baseline and monthly for chronic therapy.
• Liver enzymes: ALT/AST baseline; repeat if clinical suspicion of hepatotoxicity.
• Cardiac: ECG monitoring for patients with QTc prolongation risk or on concurrent QT‑prolonging agents.

Clinical Pearls

• Early‑onset prophylaxis: A single 10–15 mg dose 30 minutes before surgery provides optimal anti‑emetic coverage and can reduce overall postoperative oral intake.
• Bidirectional use: While predominantly a GI prokinetic, metoclopramide is often the first‑line “bridge” agent for diabetic gastroparesis pending definitive therapy (e.g., GLP‑1 agonists).
• Avoid in L‑DOPA/Turbo: Concomitant administration with levodopa–carbidopa can worsen motor symptoms in Parkinson’s; hold metoclopramide or switch to an anti‑emetic with less CNS penetration.
• Short‑Course Rule: Limit to ≤ 2 weeks for anti‑emesis; for gastroparesis, keep the total daily dose ≤ 30 mg and aim to taper within 6–8 weeks.
• Safety in Renal Failure: Use the lowest effective dose; a 5 mg PO dose may be adequate for patients with CrCl 15–30 mL/min.
• Drug–Drug Interaction: Concomitant use with other dopamine antagonists (e.g., haloperidol) magnifies EPS risk; consider alternative anti‑emetics.
• Pregnancy Consideration: Category D; discuss benefit‑risk with obstetrician; use only when no safer alternatives exist.

*Reference‑friendly note:* This drug card integrates key pharmacologic principles and clinical guidelines (e.g., American College of Gastroenterology, ASCO, and ADA) to aid medical students and practicing clinicians in decision‑making regarding metoclopramide therapy.