The proton pump (H+/K+-ATPase) is the final common pathway for acid secretion in gastric parietal cells, and inhibition of the pump blocks acid secretion almost completely. Proton pump inhibitors are pro-drugs that are rapidly absorbed from the small intestine. As weak bases, they are selectively concentrated from the circulation into the acid environment of the secretory canaliculi of the gastric parietal cells. The drugs are then converted to active derivatives by protonation and covalently bind to and irreversibly inhibit the proton pump. The return of acid secretion is dependent on the synthesis of new proton pumps. Because protonation only takes place at acid pH, these drugs have a selective action on gastric parietal cells, and proton pumps elsewhere in the body are not inhibited. A single dose of a proton pump inhibitor inhibits acid production by up to 90% for approximately 24 hours.
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