June 30, 2022

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Proton Pump Inhibitors: Risks of Long-Term Use

Proton Pump Inhibitors: Risks of Long-Term Use

Proton Pump Inhibitors: Risks of Long-Term Use. What are the risks of long-term use of proton pump inhibitors? Proton pump inhibitors (PPI) are currently the most effective class of drugs for the treatment of acid reflux. They are commonly used clinically to treat diseases such as peptic ulcer, gastroesophageal reflux disease, drug-related gastroduodenal mucosal injury, etc., which are in the heart of patients. The magical medicine for the stomach”.


Proton Pump Inhibitors: Risks of Long-Term Use


However, gastric acid is a “double-edged sword”. Excessive secretion will cause erosion of the gastric and duodenal mucosa. If PPI is used to suppress excessive gastric acid, it may increase the gastric pH (normal pH 0.9~2). The internal environment has changed. Pharmacists are often asked when they are clinically teaching patients about medication: Are there any adverse reactions to taking this “stomach-protecting medicine” for a long time? Next, the editor will list the adverse reactions related to long-term use of PPI.

1. Lack of nutrients

Insufficient gastric acid secretion can lead to obstacles to the digestion and absorption of certain nutrients. For example, calcium, iron and vitamin B12 require sufficient concentration of gastric acid to be best absorbed. Insufficient calcium absorption after long-term use of PPI causes a decrease in blood calcium concentration, induces and aggravates osteoporosis in the elderly, and increases the risk of fracture. Therefore, if it is expected to take PPI for more than one year, especially for patients with the highest dose> 1 time/d, anti-osteoporosis and regular monitoring of bone mineral density are required. Iron in food is trivalent iron, which needs to be reduced to divalent iron in gastric juice (PH<3) to be absorbed. Insufficient gastric acid secretion will affect the absorption of iron, leading to iron deficiency, which in turn causes iron deficiency anemia. In addition, gastric acid and pepsin release vitamin B12 from the vitamin B12-protein binding state in the diet, bind it to the intrinsic factors produced by parietal cells, and finally be absorbed into the blood by the terminal ileum. Therefore, too little gastric acid secretion may affect the absorption of vitamin B12.


2. Increase the risk of infection

In addition to digesting food, gastric acid also has the effect of killing bacteria and other microorganisms. The long-term use of PPI causes a decrease in the killing effect of high pH environment in the stomach on bacteria. Especially for the elderly with poor physique, the swallowing coordination function is weakened, and they are prone to choking. Once the bacteria-containing gastric contents are refluxed to the throat, it is easy to inhale the lungs by mistake and eventually cause lung infections.

3. Increase tumor risk

PPI can promote the colonization of Helicobacter pylori and cause hypergastrinemia, which may increase the risk of gastrointestinal malignancies. According to reports in the literature, the risk of esophageal cancer in patients with long-term use of PPI increased by 5 times, and the risk of gastric cancer increased by 4 times.

4. Gastrointestinal flora imbalance

In the human gastrointestinal tract, bacteria mainly exist in the distal small intestine and colon. Intestinal microbes can promote metabolism, maintain intestinal epithelial homeostasis, regulate intestinal immune function, and affect drug metabolism. Long-term application of PPI reduces the gastric acid barrier function and thus changes the normal gastrointestinal flora and the number of pathogenic bacteria. For elderly people with poor immunity, excessive growth of gastrointestinal flora can easily cause intestinal flora imbalance, resulting in diarrhea or Symptoms such as constipation.


5. Impact on other drugs:

PPI is mainly metabolized by liver P450 enzymes and is a liver drug enzyme inhibitor. If you take the following drugs at the same time: digoxin, aspirin, diazepam, warfarin, nifedipine, theophylline, statins, clarithromycin , Imipramine, etc., may slow down the metabolism of these drugs, increase the blood concentration, and enhance the efficacy.

PPI reduces the absorption of domperidone, iron agents (ferrous succinate, ferrous sulfate, etc.), bismuth agents (bismuth potassium citrate, bismuth pectin, etc.), itraconazole, and tetracycline by inhibiting gastric acid secretion.

Omeprazole has a significant inhibitory effect on clopidogrel, so the combined use of omeprazole and clopidogrel should be avoided. If PPI must be used, pantoprazole or rabeprazole can be considered.