5-HT3 receptor antagonists (ondansetron, granisetron) are first-line antiemetics for chemotherapy-induced nausea and vomiting (CINV). Their antiemetic mechanism involves blocking 5-HT3 receptors at which anatomical locations?

• A Dopamine D2 receptors in the chemoreceptor trigger zone and vagal afferents
• B NK1 receptors on neurons in the nucleus tractus solitarius and vomiting centre
• C 5-HT3 receptors on vagal afferents in the small intestine/gut AND in the chemoreceptor trigger zone (area postrema) ✓
• D H1 receptors in the vestibular nucleus and cerebellum

Explanation

Chemotherapy causes enterochromaffin cells in the gut mucosa to release large amounts of serotonin (5-HT). This 5-HT activates 5-HT3 receptors on vagal afferent neurons in the gut wall and in the chemoreceptor trigger zone (CTZ) of the area postrema, transmitting emetic signals to the vomiting centre. Ondansetron and related 5-HT3 antagonists block both the peripheral vagal afferent pathway and the CTZ component. Dopamine D2 blockade is the mechanism of metoclopramide/domperidone (used for CINV but less specific). NK1 blockade is the mechanism of aprepitant (used for delayed CINV).

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

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Written and medically reviewed by the StethoPrep medical team.