Reviews in Basic and Clinical Gastroenterology and HepatologySafety of Proton Pump Inhibitor Exposure
Section snippets
Mechanism of Action of Proton Pump Inhibitor Therapy
PPIs are prodrugs; they require activation by parietal cells in the presence of gastric acid, which leads to formation of an active sulfenamide moiety. This moiety binds irreversibly to the hydrogen potassium ATPase on the secretory canaliculus of actively secreting parietal cells, which inhibits the ability of cells to produce hydrochloric acid.2, 4, 16, 17, 18 The prodrug is systemically absorbed or delivered directly into the bloodstream, resulting in a relatively short half-life in serum;
Vitamin B12
Gastric acidity is important for the absorption of vitamin B12.39, 40 Most dietary vitamin B12 is tightly bound to protein; it is released in the stomach by gastric acid and pepsin and binds to salivary R proteins and subsequently to intrinsic factors.41 This complex remains intact until the terminal ileum, where vitamin B12 is absorbed. PPI-induced hypochlorhydria could induce malabsorption of vitamin B12 by interfering with the acid-activated proteolytic digestion of dietary protein-bound
Balancing the Risk and Benefit of PPI Therapy
PPIs have revolutionized the management of acid-related diseases. They improve outcomes in patients with peptic ulcer disease, gastroesophageal reflux, hypersecretory conditions, and nonsteroidal anti-inflammatory drug gastropathy. Although these drugs have been linked with a number of potential adverse effects, almost all the existing data in this regard are based on observational studies that are susceptible to bias and confounding. It is important to remember that all drugs carry risks and
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Conflicts of interest The authors disclose the following: Dr Metz is a consultant and receives honoraria and/or grant support from AstraZeneca, Takeda, Novartis Consumer, and Xenoport. Dr Yang discloses no conflicts.