Proton pump inhibitors (PPI) are a class of weakly basic benzimidazoles that inhibit gastric acid secretion by reducing proton pump activity in gastric mucosal wall cells, and can be used to treat GERD, peptic ulcer, gastrinoma and other related diseases. It is used to treat GERD, peptic ulcer, gastrinoma and other related diseases. Short-term adverse effects are mild and can disappear after discontinuation, so it has become one of the most commonly used drugs in clinical practice. Proton pump inhibitors (PPI) are a class of weakly alkaline benzimidazole compounds that inhibit gastric acid secretion by reducing proton pump activity in gastric mucosal wall cells, and can be used to treat GERD, peptic ulcer, gastrinoma and other related diseases. Short-term adverse effects are mild and can disappear after discontinuation, and have become one of the most commonly used drugs in clinical practice. In recent years, there are more and more reports of adverse reactions caused by long-term use of PPI, especially in elderly people over 65 years old. Some scholars have reported that the efficacy of antiplatelet drugs is reduced in patients with acute coronary syndrome who take both clopidogrel and PPI. These findings have raised concerns among physicians, especially gastroenterologists, about whether to combine PPIs and the adverse effects of long-term PPI application. 1. Adverse effects of PPI in combination with other drugs Long-term use of antiplatelet drugs in patients with coronary atherosclerotic heart disease can effectively prevent recurrence of acute coronary syndrome, while antiplatelet drugs can lead to mucosal breakdown of the gastrointestinal tract and increase the risk of gastrointestinal bleeding. To reduce the risk of GI bleeding caused by antiplatelet agents, the 2008 American College of Cardiology Foundation (ACCF)/American College of Gastroenterology (ACG)/American Heart Association (AHA) Expert Consensus recommended the use of PPI in combination with dual antiplatelet therapy in patients at risk of GI bleeding. Follow-up studies found that the incidence of adverse reactions caused by PPI in combination with clopidogrel was The incidence of adverse reactions due to PPI in combination with clopidogrel was found to be higher than that of clopidogrel alone, considering that the combination of the two may have contributed to the occurrence of adverse reactions. Further studies have found that the combination of PPI and antiplatelet agents may reduce the activity of antiplatelet agents and increase the incidence of cardiovascular events. For this reason, the 2010 ACCF/ACG/AHA consensus states that H:receptor blockers can be used when the risk of gastrointestinal bleeding is low; considering that the half-life of both PPI and clopidogrel is less than 2h, the interval between the two doses can reduce the occurrence of cardiovascular adverse events. 2. Risk of infection It is known that gastric acid is the last line of defense in the body to kill bacteria in food, and most bacteria, except H. pylori, cannot adapt to the acidic environment in the stomach. PPI can reduce gastric acid secretion, prolong gastric emptying time, increase the chance of bacteria entering the body, and increase the incidence of digestive tract and systemic infections, especially in patients with high-dose long-term use. Common infections include Clostridium difficile infection and small intestinal bacterial overgrowth, and in patients with cirrhosis combined with ascites, can increase the risk of spontaneous bacterial peritonitis. Administration of PPIs may increase the incidence of pneumonia. In patients who develop infections with PPI application, treatment may include short-term use of aluminum thioglycollate for primary gastrointestinal disease in addition to additional antibiotics. Patients should be alert to the risk of infection when applying PPI drugs for a long time, especially in elderly and immunocompromised patients. 3. Tumor risk Some studies have found that PPI can weaken the secretion of growth inhibitory hormone by gastric sinus D cells and promote the secretion of gastrin by G cells, resulting in hypergastrinemia. Increased gastrin can lead to atrophy of various tissues and stimulate the growth of in vitro cultured tumor cells, including colon cancer cells. Some large-scale studies in recent years have not found an increased risk of colon cancer in patients taking PPIs. Animal studies have found that hypergastrinemia in rats leads to the development of gastric carcinoid tumors, and hypergastrinemia can also lead to the growth of intestinal chromophores, which promote the development of carcinoid and neuroendocrine tumors and may also increase the risk of gastric cancer. In addition, some studies have shown that long-term PPI use in some patients with Barrett’s esophagus may lead to an increased risk of esophageal adenocarcinoma when gastrin levels are elevated to a certain level. Although there is no direct evidence that long-term PPI use can cause tumors, it may increase their risk and should not be ignored. For patients who must apply PPI, there is no need to choke on it, and regular examination can detect it in time. 4. Other adverse reactions Due to the inhibition of gastric acid secretion, the activity of some digestive enzymes activated by gastric acid such as pepsin is reduced. Some nutrients such as vitamin C, iron, magnesium, calcium, etc. are absorbed less, resulting in a shortage of the corresponding nutrients, especially for patients with combined gastritis. PPIs are increasingly reported to cause acute interstitial nephritis ( AIN), with omeprazole accounting for 12% of cases and being the most common single agent causing AIN. Elderly, combined renal insufficiency patients taking PPIs should be monitored for renal function. As with most other drugs, PPIs can cause allergic reactions in atopic individuals. PPI is a potent inhibitor of gastric acid secretion and should be weighed against the pros and cons of long-term and high-dose use. PPI is not a panacea for digestive disorders and may cause adverse reactions when taken irregularly over a long period of time. Although PPI is a prescription drug, it can be purchased in outpatient clinics and pharmacies, and some patients take it on their own for a long time after the PPI course due to recurrent symptoms, and most serious adverse reactions are seen in patients taking PPI for a long time. Strengthen the regulation of prescription drugs. Clinicians should weigh the effectiveness and risks of the drugs and use them carefully when giving PPI treatment to patients.