A patient with delayed gastric emptying post-vagotomy is started on metoclopramide. Which receptor combination explains its prokinetic effect in the GI tract?
- A Muscarinic M2 receptor agonism directly stimulating gastric smooth muscle contraction and pyloric relaxation
- B Motilin receptor agonism in the interdigestive state, mimicking phase III MMC activity
- C Selective 5-HT3 receptor agonism at myenteric sensory neurons, triggering peristaltic reflex activation
- D Dopamine D2 receptor antagonism in the GI tract (increases ACh release from myenteric plexus) combined with 5-HT4 receptor agonism (promotes coordinated antroduodenal peristalsis) — both contributing to enhanced propulsive motility ✓
Explanation
Metoclopramide's prokinetic action involves two distinct receptor mechanisms: (1) D2 receptor antagonism in the myenteric plexus removes dopamine's inhibitory tone on cholinergic neurons, increasing acetylcholine release and stimulating gastric and small intestinal smooth muscle; (2) 5-HT4 receptor agonism in the submucosal and myenteric plexuses facilitates ascending contraction and descending relaxation, coordinating the peristaltic reflex. Additionally, metoclopramide sensitises upper GI smooth muscle to acetylcholine. Its D2 antagonism in the chemoreceptor trigger zone (area postrema) provides the antiemetic effect. The 5-HT3 antagonism at higher doses also contributes to antiemesis. Adverse effects include extrapyramidal symptoms from nigrostriatal D2 blockade and hyperprolactinaemia.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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