PROTON PUMP INHIBITORS
Proton Pump Inhibitors
The proton pump inhibitors (PPIs) are the most potent suppressants of gastric acid secretion available and are used widely in the therapy of gastroesophageal reflux and peptic ulcer disease. PPIs are prodrugs that require gastric acid for their activation. After absorption they diffuse into the parietal cells of the stomach and accumulate in the acidic secretory canaliculi. The activated form of the PPIs binds covalently to the H+/K+-ATPase of the acid-producing parietal cell, inactivating the pump molecule that transports protons (H+ molecules) into the gastric lumen. While the half-life of the PPIs is measured in hours, the activated form is trapped in the parietal cell and inhibition of the proton pump generally lasts for 24 to 48 hours. Oral forms of the PPIs are rapidly absorbed and decrease gastric acidity by 80% to 95%, although peak inhibition may require several days. More rapid inhibition may be achieved by use of intravenous formulations. The PPIs are metabolized by the hepatic cytochrome P450 system (predominantly CYP 2C19 and 3A4), but are extremely well tolerated and associated with few adverse events. Liver injury due to PPIs has been reported, but is uncommon in view of the millions of individuals who take these agents chronically.