Proton-pump inhibition

Sustained acid hyperscretion, due either (usually) to a duodenal or pancreatic gastrinoma, or to multiple endocrine adenomata, responds well to proton pump inhibition, often requiring high doses. Resection should always be considered as a cure for those with solitary adenomata, as should operation to reverse the retained antrum syndrome (partial gastrectomy where the antrum is inadvertently retained and isolated from acid inhibition, and secretes gastrin continuously). 

Acid is important in releasing vitamin B12 from food. A minor reduction in oral cyanocobalamin absorption occurs during proton pump inhibition, potentially leading to subnormal Bi2 levels with prolonged therapy. Acid also promotes absorption of food-bound minerals (iron, calcium, zinc) however, no mineral deficiencies have been reported with proton pump inhibitor therapy. 

Li XQ, Andersson TB, Ahlstrom M, et al. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pan-toprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos 2004 32 821-827. 

H+/K+-ATPase (gastric proton pump) inhibit gastric acid secretion, irrespective of the kind of stimulation. 

Q14 An alternative drug mechanism to reduce gastric secretion is proton pump inhibition. How do proton pump inhibitors reduce secretion ... 

It may take 2-5 days of therapy with once-daily dosing to achieve the 70% inhibition ofproton pumps that is seen at steady state. Since proton pump inhibition is irreversible, acid secretion is suppressed for 24-48 hours, or more, until new proton pumps are synthesized and incorporated into the luminal membrane of parietal cells. 

Hess MW, Hoenderop JG, Bindels RJ, Drenth JP. Systematic review h)fpomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther 2012 36 405-13. 

The half-life of the a subunit has usually been inferred rather than directly measured. Thus, treatment of rats with cycloheximide resulted in a loss of ATPase activity with a half-life of 72 h [29]. Recovery from inhibition with the covalent inhibitor, omeprazole, showed a half-life of 30 h in the same series of experiments. Other workers have claimed a half-life of recovery from proton pump inhibition of as short as 15 h [30]. 

Proton pump inhibition is probably not the final therapeutic solution for several of the acid-related diseases, but it undoubtedly represents a valuable and widely accepted therapeutic principle. 

Dietary calcium is complexed to food constituents such as proteins, phosphate, and oxalate, from which it needs to be released prior to absorption. The role of gastric acid (or the lack thereof induced by commonly used proton pump inhibiting drugs) in intestinal calcium absorption is not well established, although achlorhydria can impair absorption in the fasted state. 

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