Cyclo-oxygenases

Dannenberg AJ, Altorki NK, Boyle JO, et al. Cyclo-oxygenase 2 a pharmacological target for the prevention of cancer. Lancet Oncol 2001 2 544-551. 

In the rat retina, ischemia upregulates expression of the neuronal nitric oxide synthase and cyclo-oxygenase-2 these effects can be effectively inhibited by lutein (Choi et al., 2006). 

Unfortunately, frequent exposure to NSAIDS may also cause two detrimental effects. These agents inhibit the activity of cyclo-oxygenase, an important enzyme in synthesis of gastroprotec-tive prostaglandins. More importantly, NSAIDS may cause breaks... 

Parsadaniantz, S. M. et al. Effects of the inhibition of cyclo-oxygenase 1 or 2 or 5-lipoxy-genase on the activation of the hypothalamic-pituitary-adrenal axis induced by interleukin-lbeta in the male Rat. J. Neuroendocrinol. 12, 766, 2000. 

The synthesis of eicosanoids begins with arachidonic acid (C20 4 n-6 fatty acid) which is component part of cell membranes. The synthetic pathway is outlined in Figure 4.8. A key enzyme in this process is cyclo-oxygenase (COX) which occurs in two... 

O. N. Tucker, A. J. Dannenberg, E. K. Yang and T. J. Fahey III, Bile acids induce cyclo-oxygenase-2 expression in human pancreatic cancer cell lines. Carcinogenesis, 2004, 25(3), 419. 

S. Khare, S. Cerda, R. K. Wall, F. C. von Lintig, M. Tretiakova, L. Joseph, D. Stoiber, G. Cohen, K. Nimmagadda, J. Hart, M. D. Sitrin, G. R. Boss and M. Bissonnette, Ursodeoxycholic acid inhibits Ras mutations, wild-type Ras activation, and cyclo-oxygenase-2 expression in colon cancer, Cancer Res., 2003, 63, 3517. 

Celecoxib, a non-steroidal anti-inflammatory drug, is a cyclo-oxygenase-2 selective inhibitor that is as effective as diclofenac and naproxen. It should be used for the shortest period required to control symptoms. Use is associated v/ith an increased risk of thrombotic events and the cyclo-oxygenase-2 selective inhibitors are contraindicated in cerebrovascular disease. Mobic is the proprietary preparation of meloxicam. 

Mobic is the proprietary preparation of meloxicam, a non-steroidal antiinflammatory drug, which is also a selective inhibitor of cyclo-oxygenase-2. It is therefore less likely to cause gastrointestinal side-effects than other nonsteroidal anti-inflammatory drugs. However, it is still best to administer meloxicam after food. 

Indometacin, which is a non-steroidal anti-inflammatory drug, inhibits the enzyme cyclo-oxygenase implicated in inflammatory reactions. Indometacin is more effective as an anti-inflammatory agent than ibuprofen and tends to have a higher side-effect profile, including headache, diarrhoea and gastrointestinal disturbances. Rectal administration reduces but does not prevent gastrointestinal tract disturbances. 

Naproxen, a non-steroidal anti-inflammatory drug, inhibits prostaglandin release through inhibition of the cyclo-oxygenase-2 enzyme, producing an analgesic and anti-inflammatory effect. 

Betulinic acid, an anticancer drug, the NS AID diclofenac and the cyclo-oxygenase 2 inhibitor nimesulide have all been shown to trigger MPT, leading to hepatotoxicity. 

Renal clearance is usually decreased. Renal blood flow in particular is often poised critically and the use of, for example, a non-steroidal anti-inflammatory drug may cause heart failure and/or renal failure in people with existing cardiac conditions or some preexisting degree of chronic renal failure. These non-selective inhibitors of the cyclo-oxygenase enzyme... 

Paracetamol, synonym acetaminophen, is world wide probably the most popular analgesic and antipyretic. Its mechanism of action is not well understood. It is not really an NSAID as it is only a very weak inhibitor of cyclo-oxygenase and has hardly any anti-inflammatory activity. For the same reason paracetamol gives only negligible gastrointestinal irritation and gives hardly any blockade of platelet aggregation. Paracetamol concentrations in plasma reach a peak in 30-60 minutes, and the half-life in plasma is about 2 hours. Almost 100% of... 

Kearney PM, Baigent C, Godwin J, HaUs H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis Meta-analysis of randomised trials. BMJ 2006 332(7553) 1302-8. 

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... 

V.c.1.1. Cyclo-oxygenase inhibition. Inhibition of cyclo-oxygenase reduces the level of circulating prostaglandins and neurogenic inflammation. This is the mechanism of action of nonsteroidal antiinflammatory drugs (NSAID) and aspirin. The mode of action of paracetamol is less clear (inhibition of prostaglandins in the nociceptors of the posterior horn of the spinal cord and action on the supraspinal structures implicated in nociception). 

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