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VERIFIED CONTENTAuthor: Dominika Wilk

Proton pump inhibitors are drugs that are used to treat stomach ulcers or reflux and reduce the amount of acid that the stomach produces. Although their use in the above-mentioned disease entities is justified, their long-term use may lead to the impaired absorption of some vitamins, elements, and may also be a factor increasing the risk of cancer.

Proton pump inhibitors (PPIs)are drugs that affect the parietal cells of the stomach and thereby change the acidic pH of the stomach to a more alkaline one. Parietal cells are responsible for the production of hydrochloric acid, which - in some cases, can cause ulcers or erosions (this happens, for example, during infection with Helicobacter Pyroli). To prevent the acid from destroying the delicate walls of the stomach or esophagus (when reflux and the reflux of food content into the throat), patients are given PPI to inhibit HCL secretion in order to lower too acidic pH.

Proton pump inhibitors can reduce the pH even below 4 and maintain this effect for 15-20 hours. To maintain the best effect of the drug, it is given before a meal. Medicines can therefore act on 60-70% of the active proton pumps of the parietal cells (while eating, the secretion of hydrochloric acid in the stomach increases), and not only on the 5%, which are active while resting.

When are proton pump inhibitors (PPIs) used?

PPI are most often used in the case of:

  • gastric ulcer and duodenal ulcer (or in the prevention of these diseases),
  • erosion in the stomach,
  • gastroesophageal reflux,
  • treating Helicobacter Pylori infection,
  • erosive esophagitis,
  • Zollinger-Ellison syndrome,
  • treatment with non-steroidal anti-inflammatory drugs (NSAIDs) as a form of cover for the digestive system.

Side effects of chronic PPI use

Although proton pump inhibitors are one of the most effective drugs used in the treatment of diseases of the upper gastrointestinal tract, their chronic use may lead to disordersabsorption of certain nutrients, and thus lead to disturbances in the functioning of the body.

There are also indications that PPIs can increase the number of bacterial infections, not only in the gastrointestinal tract, intensify intestinal inflammation, or lead to intestinal dysbiosis.

In addition, they may weaken or intensify the effects of other medications, and in themselves lead to serious allergic reactions.

Use of PPI and infectious complications

The effect of using proton pump inhibitors is to lower the pH of the stomach, which can lead to acidity. Hydrochloric acid is a barrier to many pathogens that are not able to grow in the stomach environment (with the exception of H. Pylori), or to pass further into the lower digestive system.

When hypochlorhydria occurs, a favorable environment is created for microbial growth, leading to an increase in infections. For example, in the gastric juice of people using PPI, oral pathogens such as Stomatoccocus, Streptoccocus and Neisseria are more common.

A good example of the adverse effects of PPIs is also the increase in infections caused by Clostridium difficile - a virulent bacterium that causes persistent diarrhea. Typically, the risk factors for contracting this bacterium are antibiotics used in excess. However, it has been noticed that at present not only people after antibiotic therapy have problems with it. They also include people who use PPIs for a long time.

To confirm this correlation, several observational studies and meta-analyzes have shown that there may be an increased increase in Clostridium difficile infections while taking proton pump inhibitors.

On the other hand, in a cohort study of 745 patients who were already infected with the Clostridium bacterium, it was found that the elderly, over 75 years of age and those who took PPI on a long-term basis, had the highest risk of recurrence.

Proton pump inhibitors and kidney disease

PPIs can adversely affect kidney function, which may result in kidney diseases such as:

  • acute kidney injury (AKI),
  • chronic kidney disease (CKD)
  • and acute tubulointerstitial nephritis.

As early as 1992, there was information that one of these drugs - omeprazole, can lead to acute kidney failure, and later medical information seemed to confirm this fact, showing the relationship between long-term use of PPI and worse kidney function.

American research conductedby Klebser et al. showed that 90 days of PPI use is enough to double the frequency of kidney damage (it was compared to the administration of H2-blockers, where such a relationship did not exist).

Another American study conducted on a very large group of 15,792 adults showed that patients taking PPIs have a 1.5 times greater risk of developing chronic kidney disease than people who do not.

PPI and hypomagnesia

It has been found that chronic PPI users tend to have low blood levels of magnesium (hypomagnesia). However, for hypomagnesia to occur, many days have to pass - according to research conducted in 2015 on 9,818 people: from 182-2618 days.

Only after this time a decrease in magnesium concentration by 0.022 mEq / L can be found. Importantly, the normal values ​​of magnesium return as soon as 4 days after discontinuing medications. However, replacing one type of PPI with another does not cause any changes in the parameters and the concentration of magnesium is still lowered.

The treatment procedure for PPI-induced hypomagnesia is that PPIs are first discontinued to restore normal magnesium values, then blood levels of this element are monitored, and the level of excretion in the urine is checked for Finally, PPI drugs are changed to H2 receptor inhibitors.

PPI and vitamin B12

There are reports that taking PPI drugs may lead to a worse absorption of vitamin B12, which in turn may increase, for example, the risk of osteoporosis. Vitamin B12 is supplied in food in combination with protein, and from this combination it is released in the stomach under the influence of proteolytic enzymes acting in an acidic environment.

If there is too little hydrochloric acid (as a result of PPI), then vitamin B12 absorption may be disturbed. It will not detach from the protein and will not be properly absorbed in the small intestine. Research on the correlation of vitamin B12 deficiency with PPI consumption is not entirely clear.

There has been too little research on this topic, and they were too short to be able to conclude whether it is really proton pump inhibitors that lead to the malabsorption of vitamin B12. Nevertheless, doctors prescribing this type of drugs take into account the level of vitamin B12 in their patients and often, especially the elderly (who most often have PPI-vitamin B12 correlation), monitor its level.

PPI use and cancer risk

In order for a cell to function properly, it must be in balance in every aspectof its functioning, including maintaining the proper pH. Taking PPIs for too long changes the secretory functions of the parietal cells, reduces the enzymatic activity of cells belonging to the upper digestive system, and thus creates favorable conditions for DNA damage and later mutation.

Changing the pH in the stomach stimulates, for example, G cells to over-secrete gastrin. This causes a trophic effect on the gastric mucosa. As you can read from several scientific reports on this subject, the chronic use of PPI increases the risk of gastric adenocarcinoma.

In addition, lowered pH leads to a situation where bacteria that would normally die in the acidic contents of the stomach live and thrive without any problems, which translates into increased production of N-nitrosamines, which are carcinogenic.

Proton pump inhibitors and hypersensitivity reactions

PPI, like other drugs, can cause hypersensitivity reactions. This type of reaction includes, first of all:

  • hives,
  • maculopapular eczema,
  • contact dermatitis,
  • photoallergic dermatitis,
  • angioedema,
  • anaphylaxis,
  • vasculitis,
  • acute allergic interstitial nephritis,
  • rash with eosinophilia,
  • autoimmune reactions,
  • as well as systemic lupus erythematosus.

Proton pump inhibitors can also, by reducing the production of gastric juice, lead to the fact that molecules of drugs or food allergens enter the intestines, and from there into the bloodstream, which will cause food allergies and IgE-dependent drugs .

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Category:

Gastrology