In general,<unk> s are well tolerated, and the incidence of short-term adverse effects is relatively low. The range and occurrence of adverse effects are similar for all of the<unk> s, though they have been reported more frequently with omeprazole. This may be due to its longer availability and, hence, clinical experience. Common adverse effects include headache, nausea, diarrhea, abdominal pain, fatigue, and dizziness. Infrequent adverse effects include rash, itch, flatulence, constipation, anxiety, and depression. Also infrequently,<unk>  use may be associated with occurrence of myopathies, including the serious reaction rhabdomyolysis. Long-term use of<unk> s requires assessment of the balance of the benefits and risks of the therapy. Various adverse outcomes have been associated with long-term<unk>  use in several primary reports, but reviews assess the overall quality of evidence in these studies as "low" or "very low". They describe inadequate evidence to establish causal relationships between<unk>  therapy and many of the proposed associations, due to study design and small estimates of effect size. Benefits outweigh risks when<unk> s are used appropriately, but when used inappropriately, modest risks become important. They recommend that<unk> s should be used at the lowest effective dose in people with a proven indication, but discourage dose escalation and continued chronic therapy in people unresponsive to initial empiric therapy. Nutritional Gastric acid is important for breakdown of food and release of micronutrients, and some studies have shown possibilities for interference with absorption of iron, calcium, magnesium, and vitamin B12. With regard to iron and vitamin B12, the data are weak and several confounding factors have been identified. Low levels of magnesium can be found in people on<unk>  therapy and these can be reversed when they are switched to H2-receptor antagonist medications. High dose or long-term use of<unk> s carries a possible increased risk of bone fractures which was not found with short-term, low dose use; the FDA included a warning regarding this on<unk>  drug labels in 2010. Gastrointestinal Some studies have shown a correlation between use of<unk> s and Clostridioides difficile infection. While the data are contradictory and controversial, the FDA had sufficient concern to include a warning about this adverse effect on the label of<unk>  medications. Concerns have also been raised about spontaneous bacterial peritonitis (SBP) in older people taking<unk> s and in people with irritable bowel syndrome taking<unk> s; both types of infections arise in these populations due to underlying conditions and it is not clear if this is a class effect of<unk> s.<unk> s may predispose an individual to developing small intestinal bacterial overgrowth or fungal overgrowth. In cirrhotic patients, large volume of ascites and reduced esophageal motility by varices can provoke GERD. Acidic irritation, in return, may induce the rupture of varices. Therefore,<unk> s are often routinely prescribed for cirrhotic patients to treat GERD and prevent variceal bleeding. However, it has been recently shown that long term use of<unk> s in patients with cirrhosis increases the risk of SBP and is associated with the development of clinical decompensation and liver-related death during long-term follow-up. There is also evidence that<unk>  use alters the composition of the bacterial populations inhabiting the gut. Although the mechanisms by which<unk> s cause these changes are yet to be determined they may have a role in the increased risk of bacterial infections with<unk>  use. These infections can include Helicobacter pylori due to this species not favouring an acid environment, leading to an increased risk of ulcers and Gastric cancer risk in genetically susceptible patients.<unk>  use in subjects who have received attempted H. pylori eradication may also be associated with an increased risk of gastric cancer. The validity and robustness of this finding, with the lack of causality, have led to this association being questioned. It is recommended that long-term<unk> s should be used judiciously after considering individual's risk–benefit profile, particularly among those with history of H. pylori infection, and that further, well-designed, prospective studies are needed. Long-term use of<unk> s is associated with the development of benign polyps from fundic glands (which is distinct from fundic gland polyposis); these polyps do not cause cancer and resolve when<unk> s are discontinued. There is concern that use of<unk> s may mask gastric cancers or other serious gastric problems.<unk>  use has also been associated with the development of microscopic colitis. Cardiovascular Associations of<unk>  use and cardiovascular events have also been widely studied but clear conclusions have not been made as these relative risks are confounded by other factors.<unk> s are commonly used in people with cardiovascular disease for gastric protection when aspirin is given for its antiplatelet actions. An interaction between<unk> s and the metabolism of the platelet<unk>  clopidogrel is known and this drug is also often used in people with cardiac disease. One suggested mechanism for cardiovascular effects is because<unk> s bind and inhibit dimethylargininase, the enzyme that degrades asymmetric dimethylarginine (ADMA), resulting in higher ADMA levels and a decrease in bioavailable nitric oxide. Other Associations have been shown between<unk>  use and an increased risk of pneumonia, particularly in the 30 days after starting therapy, where it was found to be 50% higher in community use. Other very weak associations of<unk>  use have been found, such as with chronic kidney disease, dementia and HCC. As these results were derived from observational studies, it remains uncertain whether such associations are causal relationships.
Proton-pump inhibitor
Antisialagogue
Mucoactive agent
Prokinetic agent
Galactagogue
Cholagogue
Antacid
Caloric restriction mimetic