The basis for these questions is the fact that levels of all 3 of these substances (hormones, vitamins, and elements) are in some way dependent on or related to gastric acid secretion. As such, any agent that affects gastric acid secretion may affect these specific substances, and because PPIs are potent antisecretory agents, they should in turn affect them to a greater degree.
Gastrin is a potent acid secretagogue that is released from "G" cells in the antrum of the stomach and the duodenum in response to a meal. The feedback inhibition for gastrin is acid present in the lumen of the stomach and small intestine. The use of any agent that inhibits gastric secretion of acid (H2-receptor antagonists or PPIs) will result in a rise in serum gastrin as the feedback inhibition of gastrin release is diminished. Gastrin levels are commonly elevated in patients taking PPIs, but only unusually to a significant degree. No adverse clinical events have been noted with the generally mild hypergastrinemia seen with PPI therapy during the 14 years these compounds have been in clinical use.
Serum B12 levels are in part dependent on the presence of intrinsic factor secreted by parietal cells along with acid and the subsequent binding of intrinsic factor to free cobalamin in the small intestine. PPI use decreases the secretion of acid from parietal cells and of intrinsic factor as well. Studies of B12 levels in patients taking PPIs chronically have demonstrated a clinically insignificant decrease in serum B12 levels, but there have been no reports of B12 deficiency despite 14 years of widespread use of these compounds. If one is concerned about the possibility of B12 deficiency, supplementation of this vitamin can be achieved at little cost. The need for such supplementation has never been demonstrated despite close scrutiny of this physiology over time.
Iron absorption is facilitated in part by the conversion of heme in the presence of acid to a different state. Decreased acid secretion in the presence of PPI therapy theoretically would decrease the presence of this converted iron and could lead to decreased absorption. However, iron malabsorption has never been demonstrated in patients taking PPIs.
Why have there been no clinically adverse events related to these potential physiologic perturbations despite widespread use of PPIs? The answer lies in the extent and duration of the antisecretory therapy with these compounds. In general, most of these agents inhibit acid secretion only for 10-12 hours of the day, meaning that for most of the day, normal acid secretion is taking place and these physiologic events are proceeding as expected. If an agent becomes available that truly results in achlorhydria (absent acid secretion), then these physiologic consequences may become clinically relevant and worth monitoring. Until that time, there is little likelihood of encountering a patient who develops a clinically relevant abnormality of these physiologic processes due to the fact that he or she is taking a PPI.
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PPIs seem to increase fracture risk...especially in patients over 50, or those taking high doses or for more than one year.
ReplyDeleteThe theory is that PPIs might decrease calcium absorption.
PPIs also seem to increase the risk of pneumonia and Clostridium difficile diarrhea...possibly because gastric acid suppression may allow bacterial overgrowth. There's approx one more case of community-acquired pneumonia for every 226 patients on a PPI for just 5 months.
When possible, suggest limiting PPIs to short-term...up to 14 days for H. pylori...or 4 weeks for duodenal ulcers.
Try to get PPIs stopped on hospital discharge when they're used just to prevent GI bleeding in hospitalized patients.
When stopping chronic PPIs, suggest tapering the dose and then dosing every other day for a week or longer...to avoid acid rebound. Suggest H2-blockers (ranitidine, etc) or antacids if needed for symptoms.
Continue to recommend PPIs for patients at high risk for ulcers or GI bleeding due to severe GERD, erosive esophagitis, NSAIDs, etc. Keep in mind these patients often need to take PPIs long-term.
Advise patients on long-term PPIs to get enough vit D and calcium. Suggest calcium citrate...it may be less affected by low gastric acidity.
For mild indigestion suggest an H2-blocker or antacid first. Encourage lifestyle changes...smaller meals, stop smoking, etc.
Proton-Pump Inhibitors Increase Risks for C. difficile Infection
ReplyDeleteProton-pump inhibitors (PPIs) are overprescribed, and as currently used, their harms mostly outweigh their benefits, researchers and an editorialist argue in the Archives of Internal Medicine.
In one study, researchers analyzed data on more than 100,000 patients from a tertiary-care center to examine the association between intensity of acid-suppression therapy and incidence of nosocomial Clostridium difficile infection. They found that as suppression intensity increased, so did the odds ratio of infection: from 1.0 (no suppression), to 1.53 (with histamine-2–receptor antagonists), to 1.74 (with daily PPIs), to 2.36 (with more frequent PPIs).
Another study showed the effects of introducing guidelines on PPI use for preventing nosocomial upper GI bleeding. After implementation, in-hospital as well as at-discharge prescriptions for PPIs dropped significantly.
An editorialist contends that one half to two thirds of PPIs are prescribed inappropriately and that "for most patients the adverse effects of PPIs outweigh the benefits."