1. Clinical Overview
Prochlorperazine is a piperazine phenothiazine derivative with potent antiemetic, antipsychotic, and neuroleptic properties. It acts primarily as a dopamine D2 receptor antagonist in the chemoreceptor trigger zone (CTZ) and mesolimbic pathways. In the Indian context, it is widely used for the management of severe nausea and vomiting, vertigo, and as an adjunct in psychotic disorders, though its use as a first-line antipsychotic has declined in favor of atypical agents.
| Onset | Duration | Bioavailability |
|---|---|---|
| Oral: 30 to 40 minutes for antiemetic effect; Intramuscular: 10 to 20 minutes. | Approximately 4 to 6 hours after oral administration; up to 12 hours with sustained-release forms. | Oral: Approximately 12.5% due to significant first-pass metabolism. |
2. Mechanism of Action
Prochlorperazine exerts its primary antiemetic effect by blocking dopamine D2 receptors in the chemoreceptor trigger zone (CTZ) of the area postrema, which lacks a blood-brain barrier. Its antipsychotic and neuroleptic effects are mediated through antagonism of dopaminergic (D2) transmission in the mesolimbic and mesocortical pathways of the brain. It also possesses weak anticholinergic, alpha-1 adrenergic blocking, and histamine H1 blocking properties.
3. Indications & Uses
- Severe nausea and vomiting (including post-operative, chemotherapy-induced, and radiation-induced)
- Vertigo (Meniere's disease, labyrinthitis)
- Psychotic disorders (schizophrenia, acute mania) as an adjunct therapy
4. Dosage & Administration
Adult Dosage: Nausea/Vomiting: 5-10 mg orally 3-4 times daily. Max: 40 mg/day. Vertigo: 5 mg orally twice daily to 10 mg thrice daily. Psychosis: Starting dose 5-10 mg orally 3-4 times daily; may increase gradually. Maintenance: 50-100 mg/day in divided doses.
Administration: Take with or after food to minimize gastric irritation. Swallow tablet whole with a full glass of water. Do not crush or chew. Avoid alcohol. For bedridden patients, monitor for orthostatic hypotension. Do not stop abruptly after long-term use.
5. Side Effects
Common side effects may include:
- Drowsiness/Sedation
- Dizziness
- Dry mouth
- Blurred vision
- Constipation
- Orthostatic hypotension (lightheadedness)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| CNS Depressants (Alcohol, Opioids, Benzodiazepines) | Additive CNS depression, respiratory depression, hypotension | Major |
| Anticholinergics (Trihexyphenidyl, Atropine) | Increased anticholinergic side effects (dry mouth, constipation, urinary retention); may decrease antipsychotic efficacy | Moderate |
| Levodopa, Dopamine Agonists | Mutual antagonism of therapeutic effects | Major |
| QT-prolonging drugs (Amiodarone, Sotalol, Fluoroquinolones) | Increased risk of Torsades de Pointes arrhythmia | Major |
| Antihypertensives | Potentiated hypotensive effect | Moderate |
| CYP2D6 Inhibitors (Fluoxetine, Paroxetine, Quinidine) | Increased prochlorperazine plasma levels, risk of toxicity | Moderate |
7. Patient Counselling
- DO take with food or milk if stomach upset occurs.
- DO rise slowly from sitting/lying position to avoid dizziness.
- DO inform all doctors and surgeons you are taking this medicine.
- DO keep hydrated to manage constipation.
- DONT drink alcohol.
- DONT drive or operate heavy machinery until you know how it affects you.
- DONT stop taking suddenly if used long-term; consult doctor.
- DONT expose skin to excessive sunlight; use sunscreen.
8. Toxicology & Storage
Overdose: Profound CNS depression (coma), severe extrapyramidal symptoms, agitation, restlessness, convulsions, hypothermia or hyperthermia, autonomic instability (hypotension/hypertension, tachycardia), cardiac arrhythmias (QT prolongation), and anticholinergic toxicity (dry skin, flushed face).
Storage: Store below 30°C, protected from light and moisture. Keep in the original blister pack or container. Keep out of reach of children.