Cyclooxygenases reversible inhibitors

The anti-inflammatory activity of the NSAIDs is mediated chiefly through inhibition of biosynthesis of prostaglandins (Figure 36-2). Various NSAIDs have additional possible mechanisms of action, including inhibition of chemotaxis, down-regulation of interleukin-1 production, decreased production of free radicals and superoxide, and interference with calcium-mediated intracellular events. Aspirin irreversibly acetylates and blocks platelet cyclooxygenase, while most non-COX-selective NSAIDs are reversible inhibitors. 

Which of the following is a reversible inhibitor of platelet cyclooxygenase ... 

NSAIDs other than aspirin are reversible inhibitors of cyclooxygenase. The answer is (C). 

Seibert, A single amino acid difference between cyclooxygenase-1 (COX-1) and -2 (COX-2) reverses the selectivity of COX-2 specific inhibitors, J. Biol. Chem. 271 15810... 

Stimulation of local prostaglandin production is possibly one protective mechanism as quercetin stimulates the enzyme cyclooxygenase and, in addition, the cyclooxygenase inhibitor, indomethacin, reverses me protective effect of quercetin on ethanol-induced ulceration. The increase in prostaglandin synthesis may explain me increase in the amount of mucus observed and its participation in ulcer prevention. Other possible mechanisms include me following ... 

This family of drugs works mainly by inhibiting the synthesis of prostanoids (most of which, chemically, are prostaglandins) - natural local hormones within the body, which are proinflammatory, hyperalgesic and pyrexic. The inhibitors do this by binding, reversibly or irreversibly, to an enzyme called cyclooxygenase. It is now believed that the rather different pharmacology of members within the... 

There are multiple examples of drug action that depend on enzyme inhibition, including inhibitors of acetylcholinesterase, angiotensin converting enzyme, aspartate protease, carbonic anhydrase, cyclooxygenases, dihydrofolate reductase, DNA/RNA polymerases, monoamine oxidases, Na/K-ATPase, neuraminidase, and reverse transcriptase. 

I There are more than 20 nonsteroidal antiinflammatory drugs (NSAIDS) in use. Acetylsalicylic add j (ASA), the prototype, like most other NSAIDS, is a nonselective inhibitor of the cyclooxygenases j however, it binds in an irreversible fashion, whereas the others do so in a reversible manner. 

Besides the design of synthetic molecules, several papers reported the presence of specific enzymatic reactions able to produce also in the cells compounds able to act as reversible FAAH inhibitors (Maccarrone and Finazzi-Agro, 2004a). In particular, it has been found that oxidative metabolites of AEA generated by various lipoxygenases, i.e. the hydroxyanandamides (HAEAs see 12-OH-AEA in Table 4.1), are powerful inhibitors of FAAH (van der Stelt et al., 2002). Instead, derivatives of AEA generated by cyclooxygenase-2, and termed prosta-mides, have been recently shown to be inelfective on FAAH activity (Matias et al., 2004). 

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