Ondansetron, a 5-HT3 antagonist, is the first-line antiemetic for chemotherapy-induced nausea and vomiting (CINV). The peripheral trigger zone for CINV involves 5-HT3 receptors primarily located on:

• A Gastric parietal cells secreting acid in response to chemotherapy
• B Vagal afferent nerve terminals in the gut wall (enterochromaffin cell–vagal reflex) ✓
• C Chemoreceptor trigger zone (CTZ) in the area postrema
• D Smooth muscle cells of the upper GI tract causing retrograde peristalsis

Explanation

Chemotherapy causes enterochromaffin cells in the gut mucosa to release large amounts of serotonin (5-HT), which activates 5-HT3 receptors on vagal afferent nerve terminals in the gut wall. These activate the vomiting centre via vagal input. Ondansetron primarily blocks this peripheral vagal 5-HT3 pathway, though it also has activity at the CTZ (which expresses 5-HT3 receptors). The initial emetic response to highly emetogenic chemotherapy is predominantly peripherally mediated through this entero-vagal reflex.

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

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Written and medically reviewed by the StethoPrep medical team.