A 58-year-old woman receiving highly emetogenic cisplatin chemotherapy is well protected from vomiting on day 1 with ondansetron and dexamethasone but develops significant vomiting 48 to 72 hours later. The agent added specifically to cover this delayed phase acts on which receptor?

• A Substance P / neurokinin-1 receptor antagonism in the vomiting centre pathway ✓
• B 5-HT3 receptor antagonism in the chemoreceptor trigger zone
• C D2 receptor antagonism in the area postrema
• D Histamine H1 receptor antagonism in the vestibular nuclei

Explanation

The delayed phase of chemotherapy-induced emesis, beyond 24 hours, is driven largely by substance P acting at neurokinin-1 receptors in the nucleus tractus solitarius and vomiting centre. Aprepitant, an NK-1 antagonist, is combined with a 5-HT3 antagonist plus dexamethasone precisely to cover this phase. Adding another 5-HT3 antagonist adds little, since ondansetron is weak against delayed emesis. D2 and H1 antagonists serve other emetic settings, not delayed CINV.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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