Side Effects of Proton Pump Inhibitors

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Proton pump inhibitors (PPIs) are a group of drugs whose purpose it is to reduce stomach acid. They have been used to treat a wide of gastric acid-related illnesses for more than 20 years and are known to be safe and effective—so much so that they've largely supplanted H2 blockers as the drug of choice.

This is not to say that PPIs aren't without their challenges or limitations. While most of the side effects are mild and manageable, there are a number of adverse events which can occur with long-term use or overuse. These include problems with the absorption of minerals, changes in bone density, and an increased risk for certain chronic illnesses.

How Proton Pump Inhibitors Work

Proton pump inhibitors are commonly used to treat disorders like gastroesophageal reflux disease (GERD), peptic ulcers, and erosive esophagitis, Doctors may prescribe using PPIs alone or in combination with antacids. They can also be used in combination with certain antibiotics when treating Helicobacter pylori (a bacteria commonly associated with recurring stomach ulcers).

PPIs work by binding to a cell on the wall of the stomach called the parietal cell whose purpose it is to produce hydrochloric acid (HCL). By doing so, the stomach is less able to secrete HCL, allowing ulcers to heal and reflux to subside.

PPIs differ from H2 blockers in that PPIs shut down the acid pumps while H2 blockers only block the signal that trigger acid production. Because of this, PPIs work for up to 24 hours and provide relief for up to 72 hours. H2 blockers, by contrast, work for 12 hours.

Types of Proton Pump Inhibitors

Generally speaking, one PPI doesn't differ all that much from others. They all have similar mechanisms of action and similar rates of effectiveness. Currently approved PPIs include:

  • Prilosec (omeprazole)
  • Prevacid (lansoprazole)
  • Protonix (pantoprazole)
  • Aciphex (rabeprazole)
  • Nexium (esomeprazole)
  • Dexilant (dexlansoprazole)

Despite their similarities, certain PPIs are considered more effective in treating specific conditions. For example, Dexilant and Protonix are not typically used to treat H. pylori infection; the others are. For over-the-counter heartburn relief, Prilosec and Prevacid are recommended where the others aren't.

It's important to speak with your doctor to ensure that the use of a PPI is appropriate.

Side Effects and Interactions

When taken over the short term, most of the side effects associated with PPI use are mild and transient. The most common include constipation, diarrhea, flatulence, headache, upset stomach, nausea, and vomiting.

Increasing evidence suggests that long-term use may result in more serious problems. Among them:

  • It has been suggested that PPI use can interfere with the absorption of calcium, leading to bone fractures in certain cases. In response, the U.S. Food and Drug Administration issued warnings in 2011 advising that over-the-counter PPIs should be used for no longer than two weeks at a time for up to three treatments per year.
  • Long-term PPI use has also been associated with a slight increase in the risk of community-acquired pneumonia and Clostridium difficile infection.
  • Studies have shown that the use of PPIs over 10 years have a 12.5 percent risk of developing chronic kidney disease, slightly higher than the 8.5 percent seen in the general population.
  • A similar study suggested that persons who took PPIs over seven years had a 13 percent chance of getting dementia compared to those who didn't.

The research findings highlight the fact that PPIs should only be used for short-term relief or treatment rather than as a means to prevent gastric illnesses on a long-term basis.

Many of these adverse effects appear connected to the fact that PPIs not only turn off acid pumps in the stomach but in the rest of the body, as well. This includes the part of a cell called the lysosome which uses acid to clear waste. Without the means to do so, the waste can accumulate and cause the cell to deteriorate and age. This phenomenon may account for the increases seen in the studies.

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