Review
Long-term Safety Concerns with Proton Pump Inhibitors

https://doi.org/10.1016/j.amjmed.2009.04.014Get rights and content

Abstract

Proton pump inhibitors (PPIs) are among the most widely prescribed medications worldwide. Their use has resulted in dramatic improvements in treatment of peptic ulcer disease and gastroesophageal reflux disease. Despite an acceptable safety profile, mounting data demonstrate concerns about the long-term use of PPIs. To provide a comprehensive review regarding the concerns of long-term PPI use, a literature search was performed to identify pertinent original and review articles. Despite study shortcomings, the collective body of information overwhelmingly suggests an increased risk of infectious complications and nutritional deficiencies. Data regarding any increased risk in gastric or colon malignancy are less convincing. PPIs have revolutionized the management and complications of acid-related disorders with a high margin of safety; however, with the data available, efforts to reduce the dosing of or discontinue the use of PPIs must be reassessed frequently.

Section snippets

Pharmacology of Proton Pump Inhibitors

PPIs are substituted benzimidazole derivatives that inhibit the proton pump (H+/K+ adenosine triphosphatase) in the parietal cells of the stomach. PPIs work by accumulating in the secretory canaliculus of the acid-secreting parietal cell, where they are protonated to the active form, a cationic sulfonamide. This active form then binds to a sulfhydryl group on the proton pump and, by irreversible inhibition, prevents secretion of acid into the gastric lumen. Acid secretion resumes only after new

Overuse of Proton Pump Inhibitors

A major concern about PPIs is their potential overuse and abuse. Several studies have confirmed the overuse of these agents in both inpatient and outpatient settings. Approximately 50% to 60% of prescriptions of acid-suppressive medications in hospitalized patients are found to be without appropriate indications.4, 5, 6

Side Effects of Proton Pump Inhibitors

PPIs generally cause few adverse effects. The most common side effects are headaches, nausea, abdominal pain, constipation, flatulence, and diarrhea. These side effects are usually mild, self-limiting, and unrelated to dosage or age. However, long-term side effects of PPIs have recently gained attention, and several studies have looked at various side effects that may be associated with potential long-term use of PPI. These side effects are discussed in detail.

Conclusions

PPIs are highly effective drugs that have revolutionized the management of acid-related disorders during the last 2 decades. Although the long-term use of PPIs seems to have a high margin of safety, concerns have been raised about the potential risks after long-term use.

Although several studies have investigated the potential effect of PPI therapy on vitamin B12 absorption, a firm association cannot be established. The studies are limited by their smaller size and retrospective design.

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    Funding: None.

    Conflict of Interest: None of the authors have any conflicts of interest associated with the work presented in this manuscript.

    Authorship: All authors had access to the data and played a role in writing this manuscript.

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