## Chemotherapy-Induced Nausea and Vomiting (CINV) Management **Key Point:** Aprepitant, a neurokinin-1 (NK-1) receptor antagonist, is the drug of choice for highly emetogenic chemotherapy regimens like cisplatin. ### Mechanism of Action Aprepitant blocks substance P at NK-1 receptors in the chemoreceptor trigger zone and vomiting centre, providing superior control of delayed emesis (24–120 hours post-chemotherapy). ### Comparison of Antiemetics in CINV | Drug Class | Drug | Mechanism | Best For | Limitation | |---|---|---|---|---| | **5-HT3 antagonist** | Ondansetron | Blocks serotonin at CTZ | Acute emesis (0–24 hrs) | Poor delayed emesis control | | **NK-1 antagonist** | Aprepitant | Blocks substance P | **Acute + delayed emesis** | **First-line for highly emetogenic agents** | | **Metoclopramide** | Dopamine antagonist | D2 blockade | Mild–moderate CINV | Tardive dyskinesia risk; inferior efficacy | | **Phenothiazine** | Promethazine | H1 + muscarinic blockade | Mild nausea | Sedation; not for CINV | **High-Yield:** For cisplatin (highly emetogenic), the standard regimen is **aprepitant + 5-HT3 antagonist + corticosteroid** (triple therapy). Aprepitant is essential because it controls delayed emesis that 5-HT3 antagonists alone cannot prevent. **Clinical Pearl:** Aprepitant crosses the blood–brain barrier and has a long half-life (~40 hours), allowing dosing on days 1, 3, and 5 of chemotherapy. ### Why Aprepitant is Superior 1. Controls both acute and delayed CINV 2. Effective for highly emetogenic agents (cisplatin, doxorubicin) 3. Better than 5-HT3 antagonists alone for delayed phase 4. CYP3A4 inhibitor — monitor drug interactions [cite:KD Tripathi 8e Ch 48]
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