Which antiemetic agent acts as a selective antagonist at the chemoreceptor trigger zone and is particularly effective for opioid-induced nausea and vomiting?

Explanation

## Domperidone: Mechanism and Clinical Role ### Receptor Specificity **Key Point:** Domperidone is a selective D₂ dopamine antagonist that acts exclusively at the chemoreceptor trigger zone (CTZ), which lies outside the blood-brain barrier. ### Why CTZ-Selective Action Matters - The CTZ is exquisitely sensitive to dopamine antagonism - Domperidone's large, polar structure prevents significant CNS penetration - This selectivity minimizes extrapyramidal side effects compared to metoclopramide ### Clinical Advantages **High-Yield:** Domperidone is the preferred antiemetic in opioid-induced nausea because: 1. Opioids stimulate the CTZ directly via μ-receptor activation 2. Domperidone blocks this pathway without crossing the blood-brain barrier significantly 3. No tardive dyskinesia or acute dystonia risk (unlike phenothiazines or metoclopramide at high doses) ### Comparison Table: D₂ Antagonists | Agent | Receptor Selectivity | CNS Penetration | Extrapyramidal Risk | Best Use | | --- | --- | --- | --- | --- | | Domperidone | D₂ (CTZ > striatum) | Minimal | Very low | Opioid-induced CINV | | Metoclopramide | D₂ (non-selective) | High | Moderate–high | Gastric stasis, GERD | | Prochlorperazine | D₂ + muscarinic | High | High | Post-op nausea (older agent) | | Ondansetron | 5-HT₃ antagonist | Moderate | None | Chemotherapy-induced CINV | **Clinical Pearl:** In India, domperidone is widely available and preferred in opioid palliative care because it avoids the neurological complications seen with metoclopramide, especially in elderly patients receiving chronic opioids. [cite:KD Tripathi 8e Ch 47]