Omeprazole is a prodrug that requires acid activation. The specific step in its mechanism of action is:

• A Reversible competitive inhibition of H2 receptors on the basolateral membrane of parietal cells
• B Non-competitive inhibition of the H+/K+-ATPase at neutral pH in the cytoplasm
• C Blockade of the gastrin receptor (CCK2) on parietal cells, reducing ECL cell histamine release
• D Acid-catalysed conversion to a sulfenamide in the secretory canaliculi, forming a covalent disulfide bond with cysteine residues of the H+/K+-ATPase ✓

Explanation

Omeprazole is a weak base that accumulates in the acidic secretory canaliculi of active parietal cells. At pH <3, it undergoes acid-catalysed conversion to a sulfenic acid and then to a sulfenamide (tetracyclic cation) intermediate, which covalently binds to cysteine residues (Cys813, Cys892) of the H+/K+-ATPase proton pump. This irreversible covalent inactivation persists until new pump protein is synthesised (~18 h), explaining the prolonged acid suppression. H2 blockers competitively block histamine receptors; that is distinct from PPI mechanism.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.