Dopamine Antagonist Antiemetics

Dopamine antagonist antiemetics block D2 receptors in the chemoreceptor trigger zone and gut. They suit nausea due to drugs, uraemia, hypercalcaemia, gastroparesis and many postoperative and palliative causes.

Classification. Benzamides (metoclopramide), peripherally selective (domperidone), phenothiazines (prochlorperazine, chlorpromazine, promethazine), butyrophenones (haloperidol, droperidol).

• Metoclopramide 10 mg three times daily; maximum 30 mg daily; use 5 days or less.
• Domperidone 10 mg up to three times daily.
• Prochlorperazine 5 to 10 mg two to three times daily; 12.5 mg by deep intramuscular injection; maximum 40 mg daily.
• Chlorpromazine 10 to 25 mg every 4 to 6 hours.
• Haloperidol 0.5 to 1.5 mg once or twice daily.
• Droperidol 0.625 to 1.25 mg intravenously for postoperative nausea.

Differences. Haloperidol is the most selective for drug and metabolic nausea. Domperidone is the only member with little central effect and is preferred in Parkinson disease.

• Drug-induced, uraemic and hypercalcaemic nausea: haloperidol.
• Gastric stasis: metoclopramide or domperidone.
• Vertigo and migraine: prochlorperazine, metoclopramide.
• Postoperative: droperidol or haloperidol low dose as rescue.

Selection. Avoid in mechanical obstruction and Parkinson disease, except domperidone.

Contraindications. Parkinson disease, QT prolongation, phaeochromocytoma (metoclopramide), comatose states, severe CNS depression, mechanical obstruction.

Adverse effects. Acute dystonia, akathisia, parkinsonism, tardive dyskinesia, neuroleptic malignant syndrome, sedation, hypotension, hyperprolactinaemia and QT prolongation. Antipsychotics in older adults with dementia raise mortality.

Interactions. Opposition to levodopa and dopamine agonists; additive QT drugs; CNS depressants.

Special groups.

• Pregnancy: metoclopramide and prochlorperazine acceptable short term.
• Breastfeeding: metoclopramide raises prolactin.
• Children: high dystonia risk; avoid.
• Older adults: use the lowest dose.
• Kidney impairment: halve metoclopramide when creatinine clearance is under 60 mL/min.

Monitoring. Abnormal movements, ECG when QT drugs are combined, electrolytes.

Referral and escalation. Acute dystonia: procyclidine 5 to 10 mg intramuscularly or intravenously. Rigidity with fever and altered consciousness suggests neuroleptic malignant syndrome and is an emergency.