NSAIDs withdrawn from use or testing because of hepatotoxicity or other serious adverse events include benoxaprofen, sudoxicam, isoxicam, fluproquazone, bromfenac, oxyphenbutazone and phenylbutazone (aplastic anemia), indoprofen (gastrointestinal bleeding), suprofen and zomepirac (anaphylaxis). Carprofen and phenylbutazone are available in the United States as veterinary medications. Only ibuprofen and naproxen are available over-the-counter (in the United States) the rest are by prescription only. Not all of these listed agents are currently available either in the United States or elsewhere. The pharmacologic properties of the various NSAIDS are related to their molecular structure, which can be categorized into the five classes (Table). NSAIDS are indicated in the treatment of various acute and chronic inflammatory conditions, headaches, and fever. However, more than 30 million Americans take an NSAID every year, so that despite the overall low incidence of NSAID induced hepatotoxicity, their widescale use makes them an important cause of drug induced liver injury. NSAIDS are among the most frequently prescribed drugs worldwide and rarely cause drug induced liver disease. Recently, several selective inhibitors of Cox-2 have been developed that have the antiinflammatory and analgesic efficacy of other NSAIDs, but lack the effects on gastric and renal tissue that account for a majority of their adverse events (gastrointestinal bleeding and renal insufficiency). Most NSAIDs are nonselective and inhibit both Cox-1 and Cox-2. NSAIDs act through inhibition of intracellular cyclo-oxygenase enzymes (Cox-1 and Cox-2), which cause a decrease in synthesis of the proinflammatory prostaglandins that are potent mediators of pain and inflammation. The nonsteroidal antiinflammatory drugs (NSAIDs) are a group of chemically heterogenous medications used widely in the therapy of mild-to-moderate pain and inflammation.
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