The danger of prolonged use of proton pump inhibitors

Friday 5 July 2019

Students studying the medicinal chemistry option need to be able to explain the three main ways in which excess stomach acid can be controlled (D.4 pH regulation of the stomach). The first way is straightforward neutralization with a base such as magnesium hydroxide. The other two ways involve either using H2 receptor blockers or proton pump inhibitors (PPIs). H2 receptor blockers, such as ranitidine, bind to the H2 histamine receptor in the cells of the gastric lining and prevent secretion of the acid.  PPIs, e.g. omeprazole and esomeprazole, restrict the amount of acid produced by inhibiting a particular enzyme, known as the gastric proton pump, involved in the production of the acid.

Examples of over the counter PPI antacid tablets. Prilosec contains omeprazole and nexium contains esomeprazole.

They also need to be aware of the possible side effects when taking medicines (D.1 Pharmaceutical products & drug action).  The side effects of using neutralising bases are well known (e.g. constipation) but less well known are the long term side effects of the prolonged use of H2 receptor blockers and proton pump inhibitors. Knowing the side effects of antacids is particularly important as many of these drugs can be obtained over the counter and do not need to be prescribed by a doctor. PPIs are among the most widely sold drugs in the world and many people take them unnecessarily.

A group of researchers from Washington University in St Louis has carried out a long term large scale project following a total of 214,467 patients over a ten year period some of whom were taking H2 receptor blockers whilst the others were taking PPIs. In an article published in the BMJ (British Medical Journal) they have shown that those using PPIs had a considerably higher increase in death rate compared to those using H2 receptor blockers.

The conclusion from the research is that taking PPIs is associated with an increase in cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer. Following the results from this extensive study it is recommended that PPIs sold over the counter should have a clearer warning about potential health risks, as well as a warning about the need to limit length of use, generally not to exceed 14 days. People who feel they need to take them for longer than two weeks should be advised to seek medical advice.