Generic Name

Prochlorperazine

Mechanism

• Central Dopamine D₂ antagonism
• Blocks postsynaptic D₂ receptors in the chemoreceptor trigger zone (CTZ) and vestibular nuclei, reducing nausea and vomiting.
• Peripheral antagonism
• Inhibits vagal efferent activity and reduces smooth‑muscle tone, limiting gastrointestinal dysmotility.
• Serotonergic (5‑HT₂A) and histaminic (H₁) blockade
• Contributes to anti‑emetic potency and mild sedative properties.
• Minor anticholinergic effect
• Supports anti‑emetic effect but may cause dry mouth and tachycardia.

Pharmacokinetics

• Absorption
• Oral bioavailability ~30‑40 % (first‑pass hepatic metabolism).
• Rapid on‑set when given intramuscular (IM) or rectal (suppositories) – peak plasma in 30–60 min.
• Distribution
• High lipid solubility; crosses the blood‑brain barrier.
• Protein binding ~20 %.
• Metabolism
• Predominantly hepatic via CYP2D6 → N‑N‑hydroxylated metabolites.
• Enzyme activity varies with CYP2D6 polymorphisms (poor vs. ultra‑rapid metabolizers).
• Elimination
• Renal excretion of unchanged drug and metabolites.
• Terminal half‑life 4–6 h (oral); ~10 h when given IM.

Indications

• Acute and chronic nausea/vomiting
• Post‑operative, chemotherapy‑induced, migraine, vertigo, drug‑induced, or gastro‑enteritis.
• Migraine
• Often combined with analgesics (paracetamol, NSAIDs).
• Treatment of vertigo and motion sickness
• Pre‑emptive antiemetic prophylaxis in high‑risk oncology patients.
• Adjunct to antipsychotic therapy for agitation and psychosis (older indications).

Contraindications

• Absolute contraindications:
• Known hypersensitivity to phenothiazines or sulfonamides.
• Relative contraindications
• Parkinson’s disease, uncontrolled asthma, glaucoma, gastrointestinal obstruction.
• Caution in
• Elderly or frail patients (higher risk of extrapyramidal syndrome).
• Hepatic or renal impairment (dose adjustment).
• Pregnancy (Category C; risk of extrapyramidal effects in fetus).

Dosing

• Food interaction: Food may reduce oral absorption; can be taken with or without meals.
• Co‑administration: Avoid concomitant use of strong CYP2D6 inhibitors (e.g., fluoxetine) to prevent elevated plasma levels.

Adverse Effects

• Common
• Drowsiness, dizziness, dry mouth, blurred vision.
• Mild nausea or vomiting (interestingly common due to opposing pharmacodynamics).
• Extrapyramidal
• Acute dystonia, akathisia, parkinsonism, tardive dyskinesia (rare with short courses).
• Cardiovascular
• Orthostatic hypotension, tachycardia, QTc prolongation (rare).
• Metabolic
• Hyperglycemia, weight gain (long‑term prophylaxis).
• Serious
• Neuroleptic malignant syndrome (lastingly rare).
• Severe hypersensitivity reactions; anaphylaxis.

Monitoring

• Vitals: BP, HR (especially first 24 h).
• Neurologic: Assess for tremor, rigidity, or dystonia.
• Laboratory: Routine labs rarely required; fasting glucose if used chronically.
• Medication review: Evaluate CYP2D6 inhibitors/inducers, other anticholinergics, or serotonergic agents for drug‑drug interactions.
• Pregnancy: Document gestational age and neonatal monitoring if exposure occurs.

Clinical Pearls

• Use sparingly in children: Dissolve in small volumes of water to avoid high oral doses that can precipitate dystonia.
• Key rapid‑action option: The rectal suppository form is invaluable for patients who cannot tolerate oral or IV routes during acute nausea episodes.
• Avoid in Parkinson’s: D₂ blockade may worsen parkinsonian symptoms; consider ondansetron or metoclopramide instead.
• CYP2D6 check‑point: If a patient shows unusually high sensitivity (e.g., severe sedation, extrapyramidal side‑effects) after a standard dose, suspect a CYP2D6 poor metabolizer – lower the dose or switch therapy.
• Combination therapy: Pairing with an NSAID at the onset of a migraine can substantially improve relief and shorten attack duration.
• Pregnancy & lactation: Limited human data; assume Category C and weigh benefits against potential adverse effects in fetus or neonate.
• Differential for vomiting: Rule out organic causes before relying on prochlorperazine for refractory vomiting; check for obstructive lesions, intracranial pathology, or hepatic disease.

*References are available upon request. This drug card is intended for educational purposes and does not replace clinical judgment.*