A patient with peptic ulcer disease is given omeprazole. Its mechanism of gastric acid suppression involves:
- A Competitive antagonism of histamine H2 receptors on parietal cells, blocking histamine-stimulated acid secretion
- B Stimulation of somatostatin release from D cells, which inhibits gastrin and histamine-stimulated acid secretion
- C Reversible blockade of the gastrin (CCK-B) receptor on parietal cells, reducing acid secretion
- D Irreversible covalent inhibition of the H+/K+-ATPase (proton pump) in parietal cells after conversion to a sulfenamide by the acidic canalicular environment ✓
Explanation
Omeprazole is a prodrug (benzimidazole) that is trapped and concentrated in the acidic parietal cell canaliculus (pH <2). The acid environment converts it irreversibly to its active sulfenamide form, which forms a covalent disulfide bond with cysteine residues (Cys-813, Cys-892) of the active H+/K+-ATPase (proton pump). This irreversible covalent binding blocks the final step of acid secretion regardless of stimulus (histamine, gastrin, acetylcholine). Acid suppression persists until new proton pump protein is synthesised — explaining once-daily dosing efficacy despite plasma half-life of only 1–2 hours.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.