The gastric H,K-ATPase, which pumps gastric acid, appears to be in cytoplasmic tubular membranes in the resting state and then in the microvilli of the expanded secretory canaliculus in the stimulated state of the parietal cell. When activated by stimuli such as histamine and acetylcholine, the parietal cell undergoes dramatic morphologic changes from the resting status to the stimulated state. PPIs combined with antibiotics eradicate Helicobacter pylori. All PPIs give excellent healing of peptic ulcers and produce good results in reflux esophagitis. PPIs with longer half-life promise to improve acid suppression. However, the short half-life of the drug in the blood and the requirement for acid activation impair their efficacy in acid suppression, particularly at night. Because of covalent binding, their inhibitory effects last much longer than their plasma half-life. PPIs are acid-activated prodrugs that convert to sulfenic acids or sulfenamides that react covalently with one or more cysteines accessible from the luminal surface of the ATPase. Proton pump inhibitors (PPIs) are weak bases composed of two moieties, a substituted pyridine with a primary pK a of about 4.0, which allows selective accumulation in the secretory canaliculus of the parietal cell, and a benzimidazole with a second pK a of about 1.0. The gastric H,K-ATPase is the primary target for the treatment of acid-related diseases.
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