## Mechanism Comparison: Ondansetron vs Metoclopramide ### Ondansetron (5-HT3 Antagonist) **Key Point:** Ondansetron is a selective 5-HT3 receptor antagonist that acts at two sites: 1. Chemoreceptor trigger zone (CTZ) — blocks serotonin-mediated signals 2. Gastrointestinal tract — blocks peripheral 5-HT3 receptors on vagal afferents This dual action makes it highly effective for chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea/vomiting (PONV). ### Metoclopramide (Dopamine Antagonist + Prokinetic) **Key Point:** Metoclopramide has a dual mechanism: 1. **Central:** Dopamine D2 receptor antagonism in the CTZ 2. **Peripheral:** Acetylcholine agonism → increases gastric motility and gastric emptying ### Discriminating Feature | Feature | Ondansetron | Metoclopramide | |---------|-------------|----------------| | **Primary receptor** | 5-HT3 antagonist | D2 antagonist | | **Secondary action** | None | Prokinetic (↑ gastric emptying) | | **Best for** | CINV, PONV, serotonin-mediated emesis | Gastric stasis, reflux-related nausea | | **Tardive dyskinesia risk** | None | Yes (chronic use) | | **Efficacy in mechanical obstruction** | No | Yes (if not complete) | **High-Yield:** The **selective 5-HT3 antagonism** is the defining feature that separates ondansetron from all dopamine antagonists. This specificity explains why ondansetron is preferred for CINV (chemotherapy releases serotonin from gut enterochromaffin cells). **Clinical Pearl:** Metoclopramide's prokinetic action (via acetylcholine agonism) is unique among antiemetics — it actually improves gastric emptying, whereas ondansetron does not. **Warning:** Do not confuse metoclopramide's antiemetic effect (D2 blockade at CTZ) with its prokinetic effect (peripheral acetylcholine agonism). Both contribute to its antiemetic action but via different mechanisms.
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