Nonsteroidal anti-inflammatory drug
Non-steroidal anti-inflammatory drugs[1][3] (NSAID)[1] are members of a therapeutic drug class which reduces pain,[4] decreases inflammation, decreases fever,[1] and prevents blood clots. Side effects depend on the specific drug, its dose and duration of use, but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.[5][6]
Non-steroidal anti-inflammatory drug
The term non-steroidal, common from around 1960, distinguishes these drugs from corticosteroids, another class of anti-inflammatory drugs,[7] which during the 1950s had acquired a bad reputation due to overuse and side-effect problems after their initial introduction in 1948.[8][9][10]
NSAIDs work by inhibiting the activity of cyclooxygenase enzymes (the COX-1 and COX-2 isoenzymes). In cells, these enzymes are involved in the synthesis of key biological mediators, namely prostaglandins, which are involved in inflammation, and thromboxanes, which are involved in blood clotting.
There are two general types of NSAIDs available: non-selective, and COX-2 selective.[11] Most NSAIDs are non-selective, and inhibit the activity of both COX-1 and COX-2. These NSAIDs, while reducing inflammation, also inhibit platelet aggregation and increase the risk of gastrointestinal ulcers and bleeds.[11] COX-2 selective inhibitors have fewer gastrointestinal side effects, but promote thrombosis, and some of these agents substantially increase the risk of heart attack. As a result, certain COX-2 selective inhibitors—such as rofecoxib—are no longer used due to the high risk of undiagnosed vascular disease.[11] These differential effects are due to the different roles and tissue localisations of each COX isoenzyme.[11] By inhibiting physiological COX activity, NSAIDs may cause deleterious effects on kidney function,[12] and, perhaps as a result of water and sodium retention and decreases in renal blood flow, may lead to heart problems.[13] In addition, NSAIDs can blunt the production of erythropoietin, resulting in anaemia, since haemoglobin needs this hormone to be produced.
The most prominent NSAIDs are aspirin, ibuprofen, and naproxen; all available over the counter (OTC) in most countries.[14] Paracetamol (acetaminophen) is generally not considered an NSAID because it has only minor anti-inflammatory activity. Paracetamol treats pain mainly by blocking COX-2 and inhibiting endocannabinoid reuptake almost exclusively within the brain, and only minimally in the rest of the body.[15][16]
NSAIDs may be used with caution by people with the following conditions:
NSAIDs should usually be avoided by people with the following conditions:
Interactions[edit]
NSAIDs reduce kidney blood flow and thereby decrease the efficacy of diuretics, and inhibit the elimination of lithium and methotrexate.[107]
NSAIDs cause decreased ability to form blood clots, which can increase the risk of bleeding when combined with other drugs that also decrease blood clotting, such as warfarin.[107]
NSAIDs may aggravate hypertension (high blood pressure) and thereby antagonize the effect of antihypertensives,[107] such as ACE inhibitors.[108]
NSAIDs may interfere and reduce effectiveness of SSRI antidepressants through inhibiting TNFα and IFNγ, both of which are cytokine derivatives.[109][110] NSAIDs, when used in combination with SSRIs, increase the risk of adverse gastrointestinal effects.[111] NSAIDs, when used in combination with SSRIs, increase the risk of internal bleeding and brain hemorrhages.[112]
Various widely used NSAIDs enhance endocannabinoid signaling by blocking the anandamide-degrading membrane enzyme fatty acid amide hydrolase (FAAH).[113]
NSAIDs may reduce the effectiveness of antibiotics. An in-vitro study on cultured bacteria found that adding NSAIDs to antibiotics reduced their effectiveness by around 20%.[114]
The concomitant use of NSAIDs with alcohol and/or tobacco products significantly increases the already elevated risk of peptic ulcers during NSAID therapy.[115]
Veterinary use[edit]
Research supports the use of NSAIDs for the control of pain associated with veterinary procedures such as dehorning and castration of calves. The best effect is obtained by combining a short-term local anesthetic such as lidocaine with an NSAID acting as a longer term analgesic. However, as different species have varying reactions to different medications in the NSAID family, little of the existing research data can be extrapolated to animal species other than those specifically studied, and the relevant government agency in one area sometimes prohibits uses approved in other jurisdictions.
In the United States, meloxicam is approved for use only in canines, whereas (due to concerns about liver damage) it carries warnings against its use in cats[160][161] except for one-time use during surgery.[162] In spite of these warnings, meloxicam is frequently prescribed "off-label" for non-canine animals including cats and livestock species.[163] In other countries, for example The European Union (EU), there is a label claim for use in cats.[164]
