Nonsteroidal anti-inflammatory drug
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a drug class that reduce pain, decrease fever, prevent blood clots and, in higher doses, decrease inflammation. Side effects depend on the specific drug, but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack and kidney disease.
NSAIDs work by inhibiting the activity of cyclooxygenase enzymes (COX-1 and/or COX-2). 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.
NSAIDs are useful in the management of post-operative dental pain following invasive dental procedures such as dental extraction. When not contra-indicated they are favoured over the use of paracetamol alone due to the anti-inflammatory effect they provide. When used in combination with paracetamol the analgesic effect has been proven to be improved. There is weak evidence suggesting that taking pre-operative analgesia can reduce the length of post operative pain associated with placing orthodontic spacers under local anaesthetic. Combination of NSAIDs with pregabalin as preemptive analgesia has shown promising results for decreasing post operative pain intensity.
The widespread use of NSAIDs has meant that the adverse effects of these drugs have become increasingly common. Use of NSAIDs 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.
NSAIDs 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 NSAIDs (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 NSAIDs would be responsible for up to 20 percent of hospital admissions for congestive heart failure. In people with heart failure, NSAIDs 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.
Numerous "gastro-protective" drugs have been developed with the goal of preventing gastrointestinal toxicity in people who need to take NSAIDS 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 gastic ulcer while taking NSAIDS. While these techniques may be effective, they are expensive for maintenance therapy.
Benoxaprofen, since withdrawn due to its liver toxicity, was the most photoactive NSAID 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.
Most NSAIDs act as nonselective inhibitors of the enzyme cyclooxygenase (COX), inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes. This inhibition is competitively reversible (albeit at varying degrees of reversibility), as opposed to the mechanism of aspirin, which is irreversible inhibition. COX catalyzes the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A2). Prostaglandins act (among other things) as messenger molecules in the process of inflammation. This mechanism of action was elucidated by John Vane (1927–2004), who received a Nobel Prize for his work (see Mechanism of action of aspirin).