What is the mechanism of action of proton pump inhibitors?

• A. Irreversibly inhibits the H+/K+-ATPase pump on parietal cells
• B. Reversibly inhibits the H2 receptors on parietal cells
• C. Neutralizes gastric acid
• D. Blocks potassium channels

Answer: (A)

Proton pump inhibitors work by shutting down the final step of acid production in the stomach. They target the hydrogen-potassium ATPase proton pump on the surface of gastric parietal cells. These drugs are prodrugs that become activated in the very acidic environment of the secretory canaliculi and then form a covalent bond with the proton pump. This bond irreversibly inhibits the pump, so acid secretion remains suppressed until new pumps are made by the parietal cells, leading to long-lasting reduction of gastric acid.

This is different from other agents: H2 receptor antagonists reversibly block histamine H2 receptors on parietal cells to reduce acid release, but not in an irreversible, enzyme-inhibiting way; antacids neutralize existing acid in the stomach lumen rather than stopping production; and blocking potassium channels is not how these drugs work.