Generic Name

Metoclopramide

Brand Names

*Reglan*) is a synthetic dopamine‑D₂ receptor antagonist with prokinetic and anti‑emetic properties widely used in gastrointestinal disorders and nausea/vomiting prevention.

Mechanism

• D₂ Receptor Antagonism: Blocks dopamine receptors in the chemoreceptor trigger zone (CTZ) and in the gastrointestinal tract, reducing emetic reflexes.
• 5‑HT₃ Receptor Antagonism: Inhibits serotonin‑mediated signaling, contributing to anti‑emetic effects.
• Prokinetic Effect: Enhances upper‑GI motility via antagonism of inhibitory dopaminergic pathways in the enteric nervous system, promoting gastric emptying and increasing lower‑GI sphincter tone.

Pharmacokinetics

• Absorption: Oral bioavailability ≈ 70 %; peak plasma concentration (tₘₐₓ) 30–60 min.
• Distribution: Widely distributed; crosses the blood‑brain barrier.
• Metabolism: Hepatic via CYP2D6 and CYP3A4; active metabolites include α‑methyldopa.
• Elimination: Renal excretion; half‑life 2.5–4 h (oral), 3 h (IV).
• Drug Interactions: CYP2D6 inhibitors (e.g., fluoxetine) increase systemic exposure; potent CYP3A4 inhibitors (ketoconazole) may elevate levels.

Indications

• Gastric Motility Disorders: Gastroparesis (diabetic or post‑gastric surgery), functional dyspepsia.
• Nausea/Vomiting: Post‑operative, chemotherapy‑induced, radiation‑induced, or drug‑induced.
• Pre‑anesthetic: Reduces risk of aspiration by promoting gastric emptying.
• Cerebrospinal Fluid (CSF) Drainage: Enhances CSF flow in certain neurosurgical settings.

Contraindications

• Absolute Contraindications:
• Known hypersensitivity to metoclopramide or any excipient.
• Active extrapyramidal symptoms (EPS), Parkinson’s disease.
• Relative Contraindications:
• Pregnancy (Category C, limited data).
• Breastfeeding (excreted in milk).
• Severe hepatic or renal impairment (adjust dose).
• Warnings:
• Extrapyramidal Effects: Acute dystonia, Parkinsonism, tardive dyskinesia (especially with >4 wk therapy).
• Neuroleptic Malignant Syndrome (NMS): Rare but life‑threatening.
• QT Prolongation: Rare; caution with QT‑prolonging drugs.
• Sedation: Can enhance CNS depressants.

Dosing

| Condition | Adults | Pediatrics (8 kg–25 kg) | Pediatrics (2 mg/kg/h due to risk of tachyphylaxis.
• Duration: Short‑term (< 1 month) when feasible; chronic use requires periodic evaluation for tardive dyskinesia.

Adverse Effects

• Common (≤ 10 %): Headache, drowsiness, akathisia, fatigue, insomnia, constipation.
• Serious (≤ 1 %):
• Extrapyramidal symptoms: dystonia, Parkinsonism, akathisia.
• Tardive dyskinesia: chronic use (>4 wk).
• Neuroleptic malignant syndrome: hyperthermia, rigidity, altered mental status.
• QT prolongation: arrhythmias, torsades de pointes.
• Allergic reactions: rash, angioedema.
• Pediatric considerations: Increased risk of movement disorders; monitor for signs of dystonia or Parkinsonism.

Monitoring

• Clinical: Observe for early signs of EPS and NMS, especially with long‑term therapy.
• Laboratory: Routine labs usually unnecessary; consider CBC if prolonged use.
• ECG: Baseline and periodic if combined with other QT‑prolonging agents.
• Renal/Hepatic Function: Adjust dose in CKD stage 3–5 or liver impairment.
• Therapeutic Drug Monitoring (optional): Metoclopramide levels rarely warranted.

Clinical Pearls

• “Dyskinetic Watch”: In patients on chronic reglan (>4 wk) or with pre‑existing Parkinsonism, schedule monthly checks for dyskinesia; consider discontinuation or switch to prokinetic agents lacking EPS risk (e.g., erythromycin).
• “First‑Dose Dystonia”: 2–5 % develop acute dystonia within 2 h; pre‑medicate with 10 mg promethazine or 2 mg haloperidol for high‑risk individuals.
• “Short‑Term vs Long‑Term”: Use the lowest effective dose for the shortest duration to mitigate EPS; chronic indication warrants a risk‑benefit reassessment every 3 months.
• “Pregnancy and Breastfeeding”: Category C; safe only if benefits outweigh risks; avoid during lactation due to excretion into breast milk.
• “Metoclopramide + Anticholinergics”: Avoid concomitant use (e.g., oxybutynin) as additive EPS may occur.
• “IV Administration Speed”: Rapid infusion (>2 mg/kg/h) can precipitate tachyphylaxis; dilute in 250 mL NS and infuse over ≥30 min.

Key Takeaway: Metoclopramide (*Reglan*) remains a cornerstone for acute anti‑emesis and gastric motility disorders when short‑term use is emphasized, with vigilant monitoring for extrapyramidal adverse effects.