Ondansetron is effective in chemotherapy-induced nausea and vomiting. Its mechanism is:

• A Dopamine D2 antagonism in the chemoreceptor trigger zone of the medulla
• B Selective 5-HT3 receptor antagonism in vagal afferents of the GI tract and the CTZ/NTS ✓
• C Substance P/NK1 receptor antagonism, blocking the final common emetic pathway
• D Histamine H1 antagonism in the vomiting center of the medulla

Explanation

Chemotherapeutic drugs trigger release of large amounts of serotonin (5-HT) from enterochromaffin cells in the gut. This 5-HT activates 5-HT3 receptors on vagal afferent neurons (abdominal), which send signals to the nucleus tractus solitarius and chemoreceptor trigger zone (CTZ) to initiate emesis. Ondansetron, granisetron, and palonosetron are 5-HT3 antagonists that block both the peripheral (vagal afferent) and central (CTZ) 5-HT3 receptors. They are most effective for acute-phase chemotherapy-induced emesis (first 24 hours). NK1 receptor antagonists (aprepitant) target substance P-mediated delayed emesis, and the two classes are often combined for optimal antiemetic coverage.

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

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Written and medically reviewed by the StethoPrep medical team.