A patient with irritable bowel syndrome with constipation unresponsive to osmotic laxatives is prescribed linaclotide. Its mechanism of action is:

• A Activation of chloride channels via prostaglandin EP4 receptors
• B Stimulation of enteric 5-HT4 receptors to increase peristaltic reflexes
• C Agonism at guanylate cyclase C, raising intracellular cGMP and activating CFTR-mediated chloride secretion ✓
• D Osmotic retention of water by an unabsorbed disaccharide

Explanation

Linaclotide is a peptide agonist at guanylate cyclase B on intestinal epithelium, mimicking the heat-stable enterotoxin of E coli. Increased cGMP activates CFTR chloride channels, driving chloride and water secretion into the lumen and also reducing visceral pain signaling. Lubiprostone, the tempting distractor, works differently, opening type 2 chloride channels locally via EP receptors. Prucalopride corresponds to option B and lactulose to option D.

Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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