A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors

Abstract

Proton pump inhibitors (PPIs) are known as a class of pharmaceutical agents that target H+/K+-ATPase, which is located in gastric parietal cells. PPIs are widely used in the treatment of gastric acid-related diseases including peptic ulcer disease, erosive esophagitis and gastroesophageal reflux disease, and so on. These drugs present an excellent safety profile and have become one of the most commonly prescribed drugs in primary and specialty care. Except for gastric acid-related diseases, PPIs can also be used in the treatment of Helicobacter pylori infection, viral infections, respiratory system diseases, cancer and so on. Although PPIs are mainly used short term in patients with peptic ulcer disease, nowadays these drugs are increasingly used long term, and frequently for a lifetime, for instance in patients with typical or atypical symptoms of gastroesophageal reflux disease and in NSAID or aspirin users at risk of gastrotoxicity and related complications including hemorrhage, perforation and gastric outlet obstruction. Long-term use of PPIs may lead to potential adverse effects, such as osteoporotic fracture, renal damage, infection (pneumonia and clostridium difficile infection), rhabdomyolysis, nutritional deficiencies (vitamin B12, magnesium and iron), anemia and thrombocytopenia. In this article, we will review some novel uses of PPIs in other fields and summarize the underlying adverse reactions.

Negative Association of Proton Pump Inhibitors With Subsequent Development of Breast Cancer: A Nationwide Population‐Based Study

“…Possible mechanisms have been proposed to explain the potential antitumor activity of PPIs, particularly in cancer treatment. PPIs, both in vitro and in vivo, showed considerable antitumor influences as solo agents in the treatment of metastatic breast cancer as well as other malignancies . In contrast to previous assumptions that the gastric type of proton pump expression was limited to parietal cells of the stomach epithelia, responses of breast cancer cell lines to PPIs were also mediated by gastric‐type proton pump actions (H + /K + ‐ATPase).…”

“…Among nononcological drugs, PPIs present a satisfactory safety profile and have been considered novel and promising agents that could be repurposed against tumors . Possible mechanisms have been proposed to explain the potential antitumor activity of PPIs, particularly in cancer treatment.…”

“…A beneficial effect of PPIs on nongastroenterological diseases has been prominently proposed. Because of the observed inhibition by acidic microenvironments in cancers, potential antitumor effects of PPIs have been postulated . A population‐based case‐control study in Canada reported that cumulative use of PPIs significantly reduced the subsequent risk of kidney cancer .…”

Proton pump inhibitors reduce breast cancer risk in gastric ulcer patients: A population‐based cohort study

“…PPIs are a group of antiacid drugs controlling gastric acid. These drugs have thus been emerged as a novel application to inhibit V‐ATPase activity to treat metastatic breast cancer and inhibit human prostate cancer cell invasion …”

“…These drugs have thus been emerged as a novel application to inhibit V-ATPase activity to treat metastatic breast cancer and inhibit human prostate cancer cell invasion. [4][5][6][7] Because PPIs could potentially enhance anti-tumor chemotherapy, it has also been suspected that these medicines may play a role in preventing tumor development. 8,9 We hypothesized that PPIs usage in women with peptic ulcer might have a lower risk of breast cancer.The aim of the present study was used population-based insurance claims data of Taiwan to evaluate the risk of breast cancer development associated with using PPIs in women with gastric ulcer.…”