Antiemetics and Prokinetics
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Direct answer
Antiemetics and prokinetics are drugs that suppress nausea and vomiting, or speed gastric and small bowel transit, and they are best classified by the receptor they block. The key classes for exams are 5-HT3 antagonists such as ondansetron, dopamine D2 antagonists such as metoclopramide and domperidone, and the NK1 antagonist aprepitant. Each class carries characteristic adverse effects, from QT prolongation with ondansetron to extrapyramidal reactions with metoclopramide.
What you must remember
- 5-HT3 antagonists: ondansetron, granisetron and palonosetron block vagal afferents and the chemoreceptor trigger zone, and they are first line for chemotherapy-induced nausea.
- Metoclopramide: a central and peripheral D2 antagonist that also acts as a 5-HT4 agonist, giving prokinetic action in the gut.
- Metoclopramide adverse effects: extrapyramidal effects, akathisia, tardive dyskinesia and hyperprolactinaemia.
- Domperidone: a peripheral D2 antagonist that crosses the blood-brain barrier poorly, so extrapyramidal effects are uncommon, while QT prolongation is its key risk.
- Aprepitant: an NK1 antagonist that blocks substance P, used in highly emetogenic chemotherapy, with strong CYP3A4 interactions.
- Erythromycin: a motilin receptor agonist used as a prokinetic in gastroparesis and before endoscopy for upper gastrointestinal bleeding.
- Contraindications: prokinetics are avoided where the gut is mechanically obstructed or perforated, because stimulating motility is dangerous.
- Motion sickness: cyclizine and hyoscine act on vestibular and muscarinic pathways, and their main effects are sedation and dry mouth.
Choosing an antiemetic for a patient on levodopa
A 66-year-old man with Parkinson disease on levodopa develops nausea and vomiting after starting a new medicine. The question is which antiemetic avoids worsening his parkinsonism.
| Class (example) | Receptor or site | Key adverse effect |
|---|---|---|
| 5-HT3 antagonist (ondansetron) | 5-HT3 in gut and trigger zone | Constipation, QT prolongation |
| Central D2 antagonist (metoclopramide) | D2 in trigger zone and gut, plus 5-HT4 | Extrapyramidal effects, hyperprolactinaemia |
| Peripheral D2 antagonist (domperidone) | D2 in gut, little central action | QT prolongation, hyperprolactinaemia |
| NK1 antagonist (aprepitant) | NK1 in trigger zone and brain | Fatigue, hiccups, CYP3A4 interactions |
| Antihistamine (cyclizine) | H1 and muscarinic receptors | Sedation, dry mouth |
| Motilin agonist (erythromycin) | Motilin receptor in stomach | Abdominal cramps, QT prolongation |
The table shows why receptor choice matters: a central D2 blocker is risky in parkinsonism, whereas a peripheral D2 blocker or a 5-HT3 antagonist is usually acceptable. Adverse effects follow the receptor, so the examiner expects the drug to be chosen by its mechanism.
For highly emetogenic chemotherapy, the standard approach combines an NK1 antagonist, a 5-HT3 antagonist and dexamethasone. Breakthrough nausea is then managed with a different class, such as a D2 blocker, to avoid repeating the same mechanism.
Where the examiner tests the wrong drug
Most errors come from ignoring the receptor and the patient's other conditions.
- Trap: giving metoclopramide to a patient with Parkinson disease for nausea Correct: central D2 blockade worsens parkinsonism, so domperidone or a 5-HT3 antagonist is preferred.
- Trap: using metoclopramide to stimulate motility in suspected bowel obstruction Correct: prokinetics are contraindicated in mechanical obstruction and perforation.
- Trap: treating ondansetron as harmless because it is widely used Correct: it causes dose-related QT prolongation, so ECG checks matter with other QT-prolonging drugs or electrolyte disturbance.
Frequently asked questions
Which antiemetic is preferred in Parkinson disease?
Domperidone is preferred in Parkinson disease because it is a peripheral dopamine antagonist that barely crosses the blood-brain barrier, so it does not worsen parkinsonism. Central D2 blockers such as metoclopramide and prochlorperazine should be avoided in this setting.
What is the main adverse effect of metoclopramide?
The main adverse effects of metoclopramide are extrapyramidal reactions, including acute dystonia, akathisia and tardive dyskinesia, along with hyperprolactinaemia. These arise from central D2 blockade, so the drug is used for short courses and avoided in patients with Parkinson disease.
Why is aprepitant used in chemotherapy-induced nausea?
Aprepitant blocks the NK1 receptor, which mediates the substance P signal that drives delayed vomiting after chemotherapy. It is added to a 5-HT3 antagonist and dexamethasone for highly emetogenic regimens, and it interacts with drugs metabolised by CYP3A4.
Which 5-HT3 antagonist is linked with QT prolongation?
Ondansetron is the 5-HT3 antagonist most often linked with dose-related QT prolongation, which is a recognised adverse effect of this class. ECG monitoring is advisable in patients on other QT-prolonging drugs or with electrolyte disturbance.
When is erythromycin used as a prokinetic?
Erythromycin acts as a motilin receptor agonist, so it is used to treat gastroparesis and to clear the stomach before endoscopy for upper gastrointestinal bleeding. Its adverse effects include abdominal cramps and QT prolongation, and it can interact with other drugs.