Describe the mechanism of action of proton pump inhibitors.

• A. They block H2 receptors
• B. They irreversibly inhibit H+/K+-ATPase in gastric parietal cells
• C. They neutralize gastric acid
• D. They stimulate acid production

Answer: (B)

Proton pump inhibitors work by blocking the final step of acid secretion in the stomach. They are prodrugs that become active in the acidic environment of the secretory canaliculi of gastric parietal cells, converting to a reactive form that covalently binds to the H+/K+-ATPase enzyme (the proton pump). This binding irreversibly inactivates the pump, so acid secretion is suppressed until new proton pumps are synthesized by the cell. This leads to a prolonged reduction in both basal and stimulated gastric acid production. This mechanism distinguishes them from H2 receptor antagonists, which block histamine’s effect on acid secretion, from antacids that neutralize existing acid, and from agents that would stimulate acid production.