NSAIDs Phenylbutazone

Coumarin Diazoxide, ethacrynic acid, phenylbutazone, NSAIDs... 

Drugs that affect NSAIDs include the following Bisphosphonates, cholestyramine, cimetidine, colestipol, cyclosporine, diflunisal, DMSO, fluconazole, ketoconazole, phenobarbital, phenylbutazone, probenecid, rifampin, ritonavir, salicylates, sucralfate. 

Phenylbutazone was recognised to potentiate the anticoagulant effect of warfarin as long ago as 1959. As subsequent in vitro studies confirmed that phenylbutazone displaced warfarin from its protein binding site, it was assumed that any non-steroidal antiinflammatory drug (NSAID) would enhance warfarin s anticoagulant effect in this way. However it is now known that the interaction is due instead to a stereoselective inhibition of the metabolism of warfarin. Warfarin is available as a racemic mixture of two enantiomers R and S), and of these the S enantiomer is five times more potent as an anticoagulant. Phenylbutazone inhibits the metabolism of the... 

Apart from the salicylates NSAIDs include several classes of weak acids like propionic acid derivatives such as ibuprofen, carprofen, fenbufen, fenoprofen, flurbiprofen, ketorolac, loxoprofen, naproxen, oxaprozin, tiaprofenic acid and suprofen. Phenylbutazone is the most important representative of the pyrazolon derivatives which have a bad reputation for their risk of potentially fatal bone-marrow toxicity. To the acetic acid derivatives belong in-domethacin, diclofenac and sulindac. Sulindac is a pro-drug with less toxicity than indomethacin. The enolic acids include piroxicam, droxicam and tenoxicam. Meloxicam is an analog of piroxicam and has a high selectivity for COX-2. 

Phenylbutazone (Butazolidin) is metabolized to oxy-phenbutazone (Phlogistol), and both compounds have all of the activities associated with the NSAIDs. Their use is accompanied by serious adverse reactions, such as anemia, nephritis, renal failure or necrosis, and liver damage. Because of their toxicity, they are prescribed only for the treatment of pain associated with gout or phlebitis or as a last resort for other painful inflammatory diseases resistant to newer and less toxic treatments. Interactions with a large number of other drugs... 

Methotrexate clearance can be decreased by the coadministration of NSAIDs however, this not usually a problem with the low doses of methotrexate used to treat arthritis. Methotrexate can be displaced from plasma protein binding sites by phenylbutazone, pheny-toin, sulfonylureas, and sulfonamides and certain other antibiotics. The antifolate effects of methotrexate are additive with those of other folate-inhibitory drugs, such as trimethoprim. 

Nonsteroidal anti-inelammatory DRUGS (NSAIDs) indomethacin phenylbutazone sulindac... 

Many NSAIDs (indomethacin, phenylbutazone, sulindac, naproxen, diclofenac, ibuprofen) can raise lithium levels. 

These drugs are available in many other countries but are not sold in the USA. Azapropazone (apazone), a pyrazolone derivative, is structurally related to phenylbutazone but appears less likely to cause agranulocytosis. Its half-life of 12-16 hours may be doubled in patients with decreased renal function. Carprofen is a propionic acid derivative with a half-life of 10-16 hours. The indications and adverse effects of azapropazone and carprofen are similar to those of other NSAIDs. 

Aspirin (acetylsalicyclic add) causes irreversible acetylation of cyclooxygenase and inhibits the formation of PGs. Because mammalian platelets do not have a nucleus and the ability to carry out transcription and translation, they do not have the ability to resynthesize cyclooxygenase. New platelets must be formed, which takes several days. Other nonsteroidal antiinflammatory drugs (NSAIDs), such as indomethacin, ibuprofen, and phenylbutazone, also inhibit cylooxygenase by competing with the substrate AA at the active site. 

Therapeutic uses Phenylbutazone is prescribed chiefly in shortterm therapy of acute gout and in acute rheumatoid arthritis when other NSAID agents have failed. The usefulness of phenylbutazone is limited by its toxicity. Aspirin and newer NSAIDs are superior to phenylbutazone in most applications. 

Pharmacokinetics Phenylbutazone is rapidly and completely absorbed after oral or rectal administration. Oxyphenbutazone is an active metabolite and contributes to the activity of the parent drug. Like most of the other NSAIDs, phenylbutazone is extensively bound to plasma proteins. This property causes displace-... 

METFORMIN NS AIDS Possibility oft plasma levels of metformin if there is renal impairment due to NSAIDs. Phenylbutazone is likely to i renal elimination of metformin and t plasma levels. 

Several NSAIDs such as ibuprofen, phenylbutazone, and mefenamic acid have been reported to be a contaminant in several alternative medicine preparations and these compounds cause renal toxicity as described before (Saper et al, 2004 Gabardi et al., 2007). 

Anticoagulant (warfarin) and antiplatelet agents (ticlopidine, clopidogrel) reduced platelet adhesiveness and G1 tract damage by NSAIDs increase risk of alimentary bleeding (notably with azapropazone). Phenylbutazone, and probably azapropazone, inhibit the metabolism of warfarin, increasing its effect. 

NSAIDs, in particular indomethacin, diclofenac, mepirazole, phenylbutazone, and salicylate, can promote absorption of other drugs, including insulin, ampicillin, cephalothin, cefoxitin, and cefmetazole. Most of these observations were made in the rat and frequently after rectal administration. Several mechanisms by which NSAIDs promote drug absorption have been postulated, but exact mechanisms are not known. As NSAIDs are often irritating to the GI mucosa. 

Azapropazone is structurally related to phenylbutazone and probably shares the same adverse effects gastrotoxi-city, skin reactions, headache, vertigo, edema, and renal impairment. A review of a very large series described azapropazone adverse effects in 1724 patients (18%), causing withdrawal in 3.7%. Surprisingly, however, there were no phenylbutazone-type blood dyscrasias (SED-11, 176) (1). Azapropazone should be prescribed only for patients with active rheumatic diseases who have failed to respond to other NSAIDs (2). 

Bumadizone is an NSAID that is metabolized to phenylbutazone and oxyphenbntazone. 

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