Antiemetic Drugs
On this page
Direct answer
Antiemetics are chosen by the vomiting pathway involved: 5-HT3 receptor antagonists (ondansetron, palonosetran) dominate chemotherapy-induced and postoperative nausea through vagal and central serotonin receptors; NK1 antagonists (aprepitant) add control of delayed chemotherapy emesis; dopamine D2 blockers (metoclopramide, domperidone, phenothiazines) act on the chemoreceptor trigger zone and aid gastric emptying; antihistamines and antimuscarinics (dimenhydrinate, promethazine, hyoscine) suit vestibular and motion-related vomiting; and dexamethasone and benzodiazepines are valuable adjuncts in chemotherapy and anticipatory emesis respectively.
What you must remember
- 5-HT3 antagonists: ondansetron 8 mg intravenous or oral for chemotherapy, radiotherapy and postoperative nausea; adverse effects are constipation, headache and dose-dependent QT prolongation; palonosetron has a long half-life suited to delayed emesis.
- NK1 antagonists: aprepitant (oral) and fosaprepitant (intravenous) block substance B-mediated delayed emesis; aprepitant is a CYP3A4 inhibitor and substrate — adjust co-administered steroids and watch warfarin and statins.
- Metoclopramide: D2 antagonist and prokinetic (10 mg thrice daily, maximum five days) for gastroparesis-related vomiting; extrapyramidal reactions, especially acute dystonia in the young, are treated with diphenhydramine or benztropine; contraindicated in complete bowel obstruction and phaeochromocytoma.
- Domperidone: peripheral D2 blockade without crossing the blood-brain barrier, so minimal sedation or dystonia, but QT prolongation and galactorrhoea occur.
- Vestibular and motion sickness: H1 antihistamines (dimenhydrinate, cyclizine, promethazine) plus the antimuscarinic hyoscine (scopolamine) transdermal patch — the only class effective against motion sickness; ondansetron is weak here.
- Adjuncts: dexamethasone potentiates all antiemetic classes in chemotherapy and reduces vomiting from raised intracranial pressure; benzodiazepines prevent anticipatory vomiting; olanzapine is used in highly emetogenic or refractory settings.
- Pregnancy: doxylamine with pyridoxine is first-line for nausea of pregnancy, with promethazine or metoclopramide as second line and ginger or B6 as adjuncts.
Common confusion
Ondansetron is often misapplied to motion sickness — vestibular vomiting responds to antihistamine-antimuscarinic drugs, not 5-HT3 blockade. The second distinction is metoclopramide versus domperidone: both are prokinetic D2 blockers, but metoclopramide enters the central nervous system (hence dystonia and sedation) while domperidone stays peripheral (hence QT risk instead of extrapyramidal risk).
Exam-focused takeaway
Stems pair the emetic trigger with the right receptor class — cisplatin chemotherapy gets triple therapy (5-HT3 antagonist, dexamethasone, NK1 antagonist), a bus journey gets dimenhydrinate or hyoscine, gastroparesis gets metoclopramide or domperidone, and raised intracranial pressure gets dexamethasone. Acute dystonia in a young patient given metoclopramide and QT issues with ondansetron are favourite toxicity one-liners. Learn the four pathways — vagal serotonin, CTZ dopamine, vestibular histamine-acetylcholine, and central — and the topic collapses into a simple mapping.
Frequently asked questions
Which antiemetic class is preferred for chemotherapy-induced vomiting?
5-HT3 antagonists with dexamethasone, plus an NK1 antagonist like aprepitant for highly emetogenic regimens such as cisplatin.
Why is ondansetron ineffective in motion sickness?
Motion emesis is mediated through vestibular acetylcholine and histamine pathways, which ondansetron does not block; hyoscine or antihistamines work instead.
What is the main hazard of metoclopramide?
Extrapyramidal reactions including acute dystonic reactions and tardive dyskinesia, especially in young patients — hence the five-day use limit.
How does domperidone differ from metoclopramide?
It does not cross the blood-brain barrier, avoiding central dystonia and sedation, but prolongs QT and raises prolactin causing galactorrhoea.
What is the role of aprepitant and its interaction concern?
It blocks NK1 receptors for delayed chemotherapy emesis and inhibits CYP3A4, requiring dose adjustment of co-administered dexamethasone and warfarin monitoring.
Which antiemetic is first-line in pregnancy?
Doxylamine-pyridoxine combination, supplemented if needed by promethazine or metoclopramide after the first trimester as clinically appropriate.