omeprazole

Omeprazole is a prodrug that becomes activated in the acidic environment of the parietal cell canaliculus, where it covalently and irreversibly binds the H+/K+ ATPase (proton pump), the final step in gastric acid secretion. This results in profound and long-lasting suppression of both basal and stimulated acid secretion, more potent than H2 blockers. Recovery of acid secretion requires synthesis of new proton pumps, giving PPIs a longer duration of action than their plasma half-life would suggest.

Clinical uses include GERD, peptic ulcer disease (gastric and duodenal), NSAID-induced ulcer prophylaxis, H. pylori eradication (as part of triple or quadruple therapy with antibiotics like amoxicillin, clarithromycin, and metronidazole), Zollinger-Ellison syndrome (gastrinoma causing acid hypersecretion), and stress ulcer prophylaxis in critically ill patients.

Adverse effects and considerations: Long-term use is associated with increased risk of enteric infections (C. difficile, Salmonella, Campylobacter) due to reduced gastric acid barrier, vitamin B12 deficiency (acid needed for B12 release from food), hypomagnesemia, iron malabsorption, increased risk of osteoporosis-related fractures (reduced calcium absorption), and possible increased risk of community-acquired pneumonia. Rebound acid hypersecretion can occur upon abrupt discontinuation after prolonged use. PPIs also reduce the antiplatelet efficacy of clopidogrel by inhibiting CYP2C19-mediated activation, a notable drug interaction tested on boards. Chronic PPI use can cause hypergastrinemia due to loss of negative feedback, potentially leading to enterochromaffin-like (ECL) cell hyperplasia.

Mechanistically, it's important to distinguish PPIs (omeprazole, esomeprazole, lansoprazole, pantoprazole) from H2 receptor antagonists (ranitidine, famotidine, cimetidine), which reversibly block histamine H2 receptors and are less potent. PPIs are the most effective acid-suppressing agents available and are first-line for erosive esophagitis and peptic ulcer healing.