Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diclofenac sodium is a nonsteroidal antiinflammatory drug (NSAID) that has been used in 120 countries since its introduction in Japan in 1974. It is currently the eighth largest-selling drug and the most frequently used NSAID in the world. Diclofenac, a phenylacetic acid derivative, is a potent inhibitor of cyclooxygenase enzyme activity, and may also interact with the lipoxygenase enzyme pathway, and with the release and reuptake of arachidonic acid. Diclofenac is almost completely absorbed, highly protein-bound, penetrates well into synovial fluid, and is extensively metabolized. Comparative studies have shown that diclofenac is at least equivalent in efficacy to aspirin and other NSAID when used for the treatment of rheumatic diseases such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Diclofenac also possesses potent analgesic properties. Clinical trials suggest that diclofenac has a favorable side-effect profile, excellent patient tolerability, and a lower patient dropout rate when compared with aspirin and other NSAID.
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PMID:Review of diclofenac and evaluation of its place in therapy as a nonsteroidal antiinflammatory agent. 306 24

The transsynovial distribution and tissue accumulation of tiaprofenic acid (Surgam)--a nonsteroidal anti-inflammatory agent--was studied in 55 patients scheduled for knee joint surgery. The patients suffering from rheumatoid arthritis (53), ankylosing spondylitis (1) or a chronicly irritated knee joint (1), received 300 mg of tiaprofenic acid b.i.d. starting 4 days prior to surgery. Samples of plasma, synovial fluid, fat, muscle, bone and synovial tissue were obtained simultaneously at defined times following the last dose. The samples were analyzed for tiaprofenic acid employing HPLC. Peak plasma concentrations of 28.6 micrograms/ml were achieved after 1 h, whereas synovial levels rose up to 2.8 micrograms/ml after 8 h. The time course of the concentration ratios indicates equilibration of both compartments 6 h following the last dose. Elimination occurs with half-lives of 1.9 h from plasma and 3.1 h from synovial fluid. During this period, synovial levels persist in a range sufficient for in vitro cyclooxygenase inhibition. In contrast, tiaprofenic acid does not exert marked tissue affinity, probably due to its hydrophilic properties.
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PMID:[Trans-synovial kinetics of tiaprofenic acid]. 321 65

Osteoarthritis (OA) and rheumatoid arthritis (RA) are among the most prevalent chronic illnesses and leading causes of disability in the United States. The clinical symptoms of OA and RA, pain and inflammation, are biologic processes mediated in part by prostanoids-prostaglandins, prostacyclin, and thromboxanes. The intermediate enzymes responsible for prostaglandin biosynthesis, cyclooxygenase (COX)-1 and COX-2, have been the target of arthritis therapy using nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). An understanding of the biochemistry and molecular pharmacology of COX enzymes has allowed for the development of agents that specifically inhibit COX-2. COX-2-selective inhibitors have efficacy in OA and RA that is similar to that of NSAIDs but with a lower potential for upper gastrointestinal injury, a serious side effect of nonselective NSAIDs. COX-2-selective inhibitors have been increasingly used in the treatment of OA and RA as well as other inflammatory arthropathies including ankylosing spondylitis and gout. Clinical trials with two currently available drugs, rofecoxib and celecoxib, have demonstrated efficacy comparable to nonselective NSAIDs but with a lower risk of gastrointestinal side effects. In general, these drugs are well tolerated in patients with aspirin-sensitive asthma. Rofecoxib is well tolerated in patients with sulfonamide sensitivities; further studies are needed to fully characterize the utility of celecoxib in these patients. Clinical experience shows that because of their improved GI safety, rofecoxib and celecoxib, and newer COX-2-selective inhibitors (valdecoxib, etoricoxib, parecoxib), represent a significant advance in the treatment of arthritis and other related inflammatory conditions.
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PMID:Development and clinical application of COX-2-selective inhibitors for the treatment of osteoarthritis and rheumatoid arthritis. 1208 94

Nonsteroidal antiinflammatory drugs (NSAIDs), including selective cyclooxygenase (COX)-2 inhibitors, have come to play an important role in the pharmacologic management of arthritis and pain. Clinical trials have established the efficacy of etoricoxib in osteoarthritis, rheumatoid arthritis, acute gouty arthritis, ankylosing spondylitis, low back pain, acute postoperative pain, and primary dysmenorrhea. Comparative studies indicate at least similar efficacy with etoricoxib versus traditional NSAIDs. Etoricoxib was generally well tolerated in these studies with no new safety findings during long-term administration. The gastrointestinal, renovascular, and cardiovascular tolerability profiles of etoricoxib have been evaluated in large patient datasets, and further insight into the cardiovascular tolerability of etoricoxib and diclofenac will be gained from a large ongoing cardiovascular outcomes program (MEDAL). The available data suggest that etoricoxib is an efficacious alternative in the management of arthritis and pain, with the potential advantages of convenient once-daily administration and superior gastrointestinal tolerability compared with traditional NSAIDs.
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PMID:Etoricoxib for arthritis and pain management. 1836 May 81

Ibuprofen is a non-narcotic, non-steroidal anti-inflammatory drug used for the treatment of pain, fever, and inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. It is also used for induction of closure of patent ductus arteriosus (PDA) in neonates. Although the exact mechanism of action of ibuprofen is not known, it is believed to mediate its therapeutic effects through the inhibition of cyclooxygenase and subsequently by the inhibition of prostacyclin production. As the drug has a number of side effects, which correlate to its circulating concentration, monitoring of ibuprofen in plasma or serum is desired for patients receiving high-dose therapy. Chromatographic methods are frequently used for the assay of ibuprofen, as no immunoassays are currently available.In the method described, the drug is extracted from the serum or plasma using methylene chloride and phosphate buffer (pH 6). Meclofenamic acid is used as an internal standard. The organic phase containing the drug is separated and dried under stream of nitrogen. After trimethylsilyl derivatization, analysis is done using gas-chromatography/ mass spectrometry (GC-MS). Quantification of the drug in a sample is achieved by comparing responses of the unknown sample to the responses of the calibrators using selected ion monitoring.
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PMID:Quantitation of ibuprofen in blood using gas chromatography-mass spectrometry (GC-MS). 2007 80

Indomethacin is a non-narcotic and non-steroidal anti-inflammatory drug used in the treatment of various inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. In neonates, it is also used for induction of closure of patent ductus arteriosus (PDA). Its mechanism of action is believed to be through the inhibition of cyclooxygenase. Due to narrow therapeutic window and number of side effects, it's monitoring, particularly in neonates, is recommended. In the gas chromatography method described here, the drug is extracted from serum or plasma using methylene chloride and phosphate buffer (pH 6). The methylene chloride phase containing drug is separated and dried under stream of nitrogen. The drug is derivatized using Bis-(Trimethylsilyl)trifluoroacetamide (BSTFA) with 1% TMCS (trimethylchlorosilane). The derivatized drug is analyzed using gas chromatography-mass spectrometry. Quantitation of the drug in a sample is achieved by comparing responses of the unknown sample to the responses of the calibrators using selected ion monitoring. Meclofenamic acid is used as an internal standard.
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PMID:Quantitation of indomethacin in serum and plasma using gas chromatography-mass spectrometry (GC-MS). 2007 81