The widespread use of<unk> s has meant that the adverse effects of these drugs have become increasingly common. Use of<unk> s increases risk of a range of gastrointestinal (GI) problems, kidney disease and adverse cardiovascular events. As commonly used for post-operative pain, there is evidence of increased risk of kidney complications. Their use following gastrointestinal surgery remains controversial, given mixed evidence of increased risk of leakage from any bowel anastomosis created. An estimated 10–20% of people taking<unk> s experience indigestion. In the 1990s high doses of prescription<unk> s were associated with serious upper gastrointestinal adverse events, including bleeding.<unk> s, like all medications, may interact with other medications. For example, concurrent use of<unk> s and quinolone antibiotics may increase the risk of quinolones' adverse central nervous system effects, including seizure. There is an argument over the benefits and risks of<unk> s for treating chronic musculoskeletal pain. Each drug has a benefit-risk profile and balancing the risk of no treatment with the competing potential risks of various therapies should be considered. For people over the age of 65 years old, the balance between the benefits of pain-relief medications such as<unk> S and the potential for adverse effects has not been well determined. In October 2020, the U.S. Food and Drug Administration (FDA) required the drug label to be updated for all<unk>  anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid. They are recommending avoiding<unk> s in pregnant women at 20 weeks or later in pregnancy. Combinational risk If a COX-2 inhibitor is taken, a traditional<unk>  (prescription or over-the-counter) should not be taken at the same time. Rofecoxib (Vioxx) was shown to produce significantly fewer gastrointestinal adverse drug reactions (ADRs) compared with naproxen. The study, the VIGOR trial, raised the issue of the cardiovascular safety of the coxibs (COX-2 inhibitors). A statistically significant increase in the incidence of myocardial infarctions was observed in patients on rofecoxib. Further data, from the APPROVe trial, showed a statistically significant relative risk of cardiovascular events of 1.97 versus placebo—which caused a worldwide withdrawal of rofecoxib in October 2004. Use of methotrexate together with<unk> s in rheumatoid arthritis is safe, if adequate monitoring is done. Cardiovascular<unk> s, aside from aspirin, increase the risk of myocardial infarction and stroke. This occurs at least within a week of use. They are not recommended in those who have had a previous heart attack as they increase the risk of death or recurrent MI. Evidence indicates that naproxen may be the least harmful out of these.<unk> s aside from (low-dose) aspirin are associated with a doubled risk of heart failure in people without a history of cardiac disease. In people with such a history, use of<unk> s (aside from low-dose aspirin) was associated with a more than 10-fold increase in heart failure. If this link is proven causal, researchers estimate that<unk> s would be responsible for up to 20 percent of hospital admissions for congestive heart failure. In people with heart failure,<unk> s increase mortality risk (hazard ratio) by approximately 1.2–1.3 for naproxen and ibuprofen, 1.7 for rofecoxib and celecoxib, and 2.1 for diclofenac. On 9 July 2015, the Food and Drug Administration (FDA) toughened warnings of increased heart attack and stroke risk associated with<unk> s<unk> s) other than aspirin. Possible erectile dysfunction risk A 2005 Finnish survey study found an association between long term (over 3 months) use of<unk> s and erectile dysfunction. A 2011 publication in The Journal of Urology received widespread publicity. According to the study, men who used<unk> s regularly were at significantly increased risk of erectile dysfunction. A link between<unk>  use and erectile dysfunction still existed after controlling for several conditions. However, the study was observational and not controlled, with low original participation rate, potential participation bias, and other uncontrolled factors. The authors warned against drawing any conclusion regarding cause. Gastrointestinal The main adverse drug reactions (ADRs) associated with<unk>  use relate to direct and indirect irritation of the gastrointestinal (GI) tract.<unk> s cause a dual assault on the GI tract: the acidic molecules directly irritate the gastric mucosa, and inhibition of COX-1 and COX-2 reduces the levels of protective prostaglandins. Inhibition of prostaglandin synthesis in the GI tract causes increased gastric acid secretion, diminished bicarbonate secretion, diminished mucus secretion and diminished trophic effects on the epithelial mucosa. Common gastrointestinal side effects include: * Nausea or vomiting * Indigestion * Gastric ulceration or bleeding * Diarrhea Clinical<unk>  ulcers are related to the systemic effects of<unk>  administration. Such damage occurs irrespective of the route of administration of the<unk>  (e.g., oral, rectal, or parenteral) and can occur even in people who have achlorhydria. Ulceration risk increases with therapy duration, and with higher doses. To minimize GI side effects, it is prudent to use the lowest effective dose for the shortest period of time—a practice that studies show is often not followed. Over 50% of patients who take<unk> s have sustained some mucosal damage to their small intestine. The risk and rate of gastric adverse effects is different depending on the type of<unk>  medication a person is taking. Indomethacin, ketoprofen, and piroxicam use appear to lead to the highest rate of gastric adverse effects, while ibuprofen (lower doses) and diclofenac appear to have lower rates. Certain<unk> s, such as aspirin, have been marketed in enteric-coated formulations that manufacturers claim reduce the incidence of gastrointestinal ADRs. Similarly, some believe that rectal formulations may reduce gastrointestinal ADRs. However, consistent with the systemic mechanism of such ADRs, and in clinical practice, these formulations have not demonstrated a reduced risk of GI ulceration. Numerous "gastro-protective" drugs have been developed with the goal of preventing gastrointestinal toxicity in people who need to take<unk> s on a regular basis. Gastric adverse effects may be reduced by taking medications that suppress acid production such as proton pump inhibitors (e.g.: omeprazole and esomeprazole), or by treatment with a drug that mimics prostaglandin in order to restore the lining of the GI tract (e.g.: a prostaglandin analog misoprostol). Diarrhea is a common side effect of misoprostol, however, higher doses of misoprostol have been shown to reduce the risk of a person having a complication related to a gastric ulcer while taking<unk> s. While these techniques may be effective, they are expensive for maintenance therapy. Hydrogen sulfide<unk>  hybrids prevent the gastric ulceration/bleeding associated with taking the<unk> s alone. Hydrogen sulfide is known to have a protective effect on the cardiovascular and gastrointestinal system.<unk>  bowel disease<unk> s should be used with caution in individuals with<unk>  bowel disease (e.g., Crohn's disease or ulcerative colitis) due to their tendency to cause gastric bleeding and form ulceration in the gastric lining. Renal<unk> s are also associated with a fairly high incidence of adverse drug reactions (ADRs) on the kidney and over time can lead to chronic kidney disease. The mechanism of these kidney ADRs is due to changes in kidney blood flow. Prostaglandins normally dilate the afferent arterioles of the glomeruli. This helps maintain normal glomerular perfusion and glomerular filtration rate (GFR), an indicator of kidney function. This is particularly important in kidney failure where the kidney is trying to maintain renal perfusion pressure by elevated angiotensin II levels. At these elevated levels, angiotensin II also constricts the afferent arteriole into the glomerulus in addition to the efferent arteriole it normally constricts. Since<unk> s block this prostaglandin-mediated effect of afferent arteriole dilation, particularly in kidney failure,<unk> s cause unopposed constriction of the afferent arteriole and decreased RPF (renal perfusion flow) and GFR. Common ADRs associated with altered kidney function include: * Sodium and fluid retention * Hypertension (high blood pressure) These agents may also cause kidney impairment, especially in combination with other nephrotoxic agents. Kidney failure is especially a risk if the patient is also concomitantly taking an ACE inhibitor (which removes angiotensin II's vasoconstriction of the efferent arteriole) and a diuretic (which drops plasma volume, and thereby RPF)—the so-called "triple whammy" effect. In rarer instances<unk> s may also cause more severe kidney conditions: * Interstitial nephritis * Nephrotic syndrome * Acute kidney injury * Acute tubular necrosis * Renal papillary necrosis<unk> s in combination with excessive use of phenacetin or paracetamol (acetaminophen) may lead to analgesic nephropathy. Photosensitivity Photosensitivity is a commonly overlooked adverse effect of many of the<unk> s. The 2-arylpropionic acids are the most likely to produce photosensitivity reactions, but other<unk> s have also been implicated including piroxicam, diclofenac, and benzydamine. Benoxaprofen, since withdrawn due to its liver toxicity, was the most photoactive<unk>  observed. The mechanism of photosensitivity, responsible for the high photoactivity of the 2-arylpropionic acids, is the ready decarboxylation of the carboxylic acid moiety. The specific absorbance characteristics of the different chromophoric 2-aryl substituents, affects the decarboxylation mechanism. During pregnancy While<unk> s as a class are not direct teratogens, use of<unk> s in late pregnancy can cause premature closure of the fetal ductus arteriosus and kidney ADRs in the fetus. Thus,<unk> s are not recommended during the
Nonsteroidal anti-inflammatory drug
Antiarthritics
Anticorticosteroid
Disease-modifying antirheumatic drug
Antiviral drug
Chiral drugs
Antiprion drug
Antiplatelet drug