Proton Pump Inhibitors

The proton pump inhibitors available in the United States are omeprazole (Prilosec), lansoprazole (Prevacid), pan-toprazole (Protonix), rabeprazole (Aciphex), and es-omeprazole (Nexium). These are substituted benzimida-zole prodrugs, which accumulate on the luminal side of parietal cells' secretory canaliculi. They become activated by acid transport and then bind covalently to the actual H+-K+ ATPase enzymes (proton pumps) irreversibly blocking them. These drugs markedly inhibit gastric acid secretion. New proton pumps are continuously formed, and thus no tolerance develops. Peptic ulcers and erosive esophagitis that are resistant to other therapies will frequently heal when these agents are used. The proton pump inhibitors are also used to treat patients with Zollinger-Ellison syndrome, which is the result of a gastrin-hypersecreting neuroendocrine tumor.

The prodrugs are unstable in the presence of acid and therefore must be administered as an enteric-coated preparation or as a buffered suspension. Pantoprazole is also available in an intravenous formulation. The most commonly reported side effects are diarrhea and headache. Hypergastrinemia has been noted as a reaction to the marked reduction in acid secretion. Gastric carcinoid tumors have developed in rats but not in mice or in human volunteers, even after long-term use.

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