5-HT3 receptor antagonists (ondansetron, granisetron) are particularly effective for chemotherapy-induced nausea and vomiting (CINV) because:
- A Chemotherapy directly stimulates the chemoreceptor trigger zone (CTZ) D2 receptors; 5-HT3 blockade at D2 receptors prevents this
- B Cytotoxic drugs cause enterochromaffin cell serotonin release in the gut that activates 5-HT3 receptors on vagal afferents triggering the vomiting reflex; 5-HT3 antagonists block this in both the gut and area postrema ✓
- C 5-HT3 antagonists inhibit histamine H1 receptors in the vestibular nucleus that mediate nausea
- D Serotonin reuptake inhibition by these drugs reduces CNS anxiety that amplifies nausea perception
Correct answer: B. Cytotoxic drugs cause enterochromaffin cell serotonin release in the gut that activates 5-HT3 receptors on vagal afferents triggering the vomiting reflex; 5-HT3 antagonists block this in both the gut and area postrema
Explanation
Cisplatin and other highly emetogenic chemotherapy damage the gut mucosa, triggering release of serotonin from enterochromaffin cells. This 5-HT activates 5-HT3 receptors on vagal afferent fibres projecting to the nucleus tractus solitarius and directly in the chemoreceptor trigger zone (CTZ)/area postrema, initiating vomiting. 5-HT3 receptor antagonists block both peripheral (vagal) and central (CTZ) serotonergic inputs, effectively controlling acute CINV. NK1 antagonists (aprepitant) cover delayed CINV via substance P.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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