A patient receiving cisplatin-based chemotherapy develops intractable nausea and vomiting that does not respond to metoclopramide. The oncologist switches to ondansetron. At which receptor does ondansetron exert its primary antiemetic effect?

• A Dopamine D2 receptor in the chemoreceptor trigger zone
• B Histamine H1 receptor in the vomiting centre
• C Serotonin 5-HT3 receptor on vagal afferents and in the chemoreceptor trigger zone ✓
• D Muscarinic M1 receptor in the nucleus tractus solitarius

Explanation

Ondansetron is a selective 5-HT3 receptor antagonist. Cisplatin and other chemotherapeutic agents cause release of serotonin (5-HT) from intestinal enterochromaffin cells, which activates 5-HT3 receptors on vagal afferents projecting to the nucleus tractus solitarius and on the chemoreceptor trigger zone (CTZ), triggering emesis. Blockade of 5-HT3 receptors at both peripheral and central sites prevents this. Metoclopramide and domperidone act on D2 receptors. Antihistamines act on H1 receptors; hyoscine acts on M1 receptors for motion sickness.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.