Antiemetic Drugs

Antiemetic drugs suppress nausea and vomiting by blocking receptors in the chemoreceptor trigger zone, vomiting centre, vestibular system and gut. Effective use depends on the cause because each class works at different receptors.

Receptors. Dopamine D2, serotonin 5HT3, neurokinin 1, histamine H1, muscarinic M1, and cannabinoid. Dexamethasone and benzodiazepines act by less defined mechanisms.

• 5HT3 antagonists: ondansetron 4 to 8 mg.
• Dopamine antagonists: metoclopramide 10 mg; prochlorperazine; haloperidol 0.5 to 1.5 mg.
• NK1 antagonists: aprepitant, fosaprepitant.
• Antihistamines: cyclizine 50 mg; promethazine 12.5 to 25 mg.
• Anticholinergics: hyoscine hydrobromide.
• Others: dexamethasone, olanzapine 5 to 10 mg, doxylamine with pyridoxine.

Differences. Combine drugs from different classes. Do not combine two from the same class.

• Gastroenteritis: ondansetron 4 to 8 mg orally or intravenously every 8 hours; metoclopramide 10 mg is an alternative.
• Postoperative: ondansetron 4 mg and dexamethasone 4 mg intravenously at induction; rescue with a different class.
• Chemotherapy: high risk, a 5HT3 antagonist, dexamethasone and an NK1 antagonist, often with olanzapine; moderate risk, a 5HT3 antagonist and dexamethasone; low risk, a single agent.
• Drug, uraemic or metabolic nausea: haloperidol 0.5 to 1.5 mg once or twice daily.
• Vestibular and motion: cyclizine 50 mg every 8 hours or hyoscine hydrobromide.
• Raised intracranial pressure: cyclizine with treatment of the cause.
• Bowel obstruction: cyclizine or haloperidol; avoid metoclopramide in complete mechanical obstruction.
• Pregnancy: doxylamine with pyridoxine, then cyclizine or promethazine, then metoclopramide or ondansetron. In hyperemesis give thiamine 100 mg daily before dextrose.
• Migraine: metoclopramide 10 mg intravenously.

Adverse effects. Sedation, anticholinergic effects, extrapyramidal reactions, QT prolongation, constipation.

Interactions. Cumulative QT prolongation with ondansetron, haloperidol, domperidone and macrolides; serotonin toxicity with 5HT3 antagonists and other serotonergic drugs.

Special groups.

• Pregnancy: step from doxylamine with pyridoxine to cyclizine or promethazine, then metoclopramide or ondansetron; avoid prolonged dopamine antagonists.
• Breastfeeding: sedating antihistamines may sedate the infant.
• Children: avoid metoclopramide and promethazine in the very young.
• Older adults: avoid anticholinergic antiemetics where possible.
• Kidney and liver impairment: reduce doses of metoclopramide and ondansetron.

Monitoring. Hydration, electrolytes (potassium, magnesium) and ECG when QT drugs are combined.

Referral and escalation. Persistent vomiting with abdominal pain, haematemesis, neurological signs, dehydration, or hyperemesis with weight loss over 5 percent needs admission.