Omeprazole is a proton pump inhibitor (PPI) that is itself inactive. The mechanism of its activation and irreversible inhibition of the proton pump is:

• A Omeprazole is a prodrug; in the acidic secretory canaliculus of parietal cells it is protonated to sulfenamide (tetracyclic), which covalently binds SH groups (Cys813, Cys892) of H+/K+-ATPase ✓
• B Omeprazole is absorbed unchanged and directly blocks the ATP-binding site of H+/K+-ATPase
• C Omeprazole is converted by CYP2C19 in the liver to the active sulfenamide before reaching the parietal cell
• D Omeprazole blocks histamine H2 receptors on the basolateral membrane, reducing cAMP-driven proton pump activation

Explanation

Omeprazole is a prodrug: absorbed as the inactive form, it accumulates in the highly acidic secretory canaliculus of parietal cells (pH ~1–2), where it spontaneously rearranges to the active sulfenamide (tetracyclic cationic compound). This reactive sulfenamide forms covalent disulfide bonds with cysteine residues on the luminal surface of the H+/K+-ATPase alpha-subunit (principally Cys813 and Cys892). This irreversible binding inactivates pumps for 18–24 hours until new pumps are synthesised. Acid suppression recovers over 2–3 days after stopping the drug.

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

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Written and medically reviewed by the StethoPrep medical team.