Cyclo-oxygenase-2 COX

Unfortunately, the cyclo-oxygenase-2-(COX-2-) selective inhibitors have been shown to carry an increased risk of thromboembolic events in long-term use, which limits their usefulness. For other NSAIDs... 

Aspirin, or acetylsalicylic acid, has been used for more than 100 years for its analgesic, antipyretic and anti-inflammatory activities. More recently an array of NSAIDs have been developed and introduced into the clinic. For the most part these drugs are well tolerated, but a variety of Type A ADRs, some of which can be life threatening, have been reported for these drugs. An important mechanism of action of the NSAIDs efS-cacy is the inhibition of the enzyme cyclo-oxygenase 2 (COX-2), which prevents the overproduction of prostaglandins and decreases the pain, fever, and inflammation associated with COX-2 activity. 

Cyclo-oxygenase 2 (COX-2) has been proposed as a target for noninvasive imaging of inflammation and cancer. This is based on the notion that COX is the critical enzyme in prostaglandin synthesis. COX-2, a membrane-bound enzyme, has potent inflammatory effects but is also overexpressed in colon, breast, lung, and other cancers. COX-2 overexpression results in decreased apoptosis and increased cell migration and proliferation. 

Cyclo-oxygenase-2 (COX-2) selective inhibitors (coxibs) were developed because of reduced gastrointestinal adverse reactions compared with traditional non-selective NSAIDs, but later evidence suggested an increased cardiovascular risk [1, 2 ]. More information has recently been published about adverse events in patients taking COX-2 selective and non-selective NSAIDs. 

This validated HPLC-MS technique has been utilized in a pharmacokinetic study of lumiracoxib, a cyclo-oxygenase-2 (COX-2) selective inhibitor in development for the treatment of rheumatoid arthritis, osteoarthritis, and acute pain. Levels of the drug and its metabolites (4 -hydroxy-lumiracoxib and 5-carboxy-4 -hydroxy-lumiracoxib) were determined in plasma and synovial fluid. The pharmacokinetic curves were interpreted by two independent methods. Both absorption (peak plasma concentration after 2 h) and decay (plasma half-life 6 h) are relatively fast. Lumiracoxib concentrations were first higher in the plasma, later in the synovial fluid (peak drug concentrations in the latter were about three times higher). Concentrations of 4 -hydroxy-lumiracoxib, the active COX-2 selective metabolite, remained low in comparison with parent drug in both plasma and synovial... 

Non-steroidal anti-inflammatory agents, including ibuprofen and selective Cox-2 inhibitors (cyclo-oxygenase 2), can increase plasma lithium concentrations add with caution to patients stabilized on lithium... 

Hippisley-Cox J, Coupland C, Hippisley-Cox J, Coupland C. Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitorsor conventional non-steroidal anti-inflammatory drugs population based nested case-control analysis.. BMJ 2005 330 1366. 

COX-2 [Cyclo-oxygenase-2] An enzyme that catalyzes the synthesis of prostaglandins from the polyunsaturated fatty acid arachidonic acid. COX-2 is responsible for the production of prostaglandins attributable to stimulation (i.e., levels are induced in times of inflammation). Cyclooxygenase activity is inhibited by aspirin-like drugs, accounting for their anti-inflammatory effects. 

Aspirin acts by interfering with the synthesis of prostaglandins, which are connected to the causes of inflammation and fever. In particular it is an inhibitor of the cyclo-oxygenase (Cox-2) enzyme. Studies of the use of aspirin as an anticlotting agent suggest that half an aspirin tablet per day may reduce the risk of heart attack and stroke in some people.3... 

Manna et al., 2000). In addition, A77 1726 exerts a direct inhibitory effect on cyclo-oxygenase (COX)-2 activity, both in intro and in vivo (Hamilton et al.,... 

Resveratrol has been reported to have chemo-preventive activity in a mouse model of carcinogenesis, but there is a concentration-dependent effect, and at the concentrations used in vitro the effect is predominantly antiproliferative. It has also been reported to have mitochondrial-dependent apoptotic activity against a variety of cell lines. Resveratrol has been reported to inhibit the constitutive COX-1, but it is not clear whether it inhibits the inducible COX-2. These cyclo-oxygenases stimulate tumor growth by acting on cell proliferation, angiogenesis, and immuno-suppression.f °° ... 

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