Cyclooxygenase enzymes NSAIDs’ inhibition

NSAIDs inhibit cyclooxygenases (COX), the enzymes that catalyze the transformation of arachidonic acid (a ubiquitous cell component generated from phospholipids) to prostaglandins and thromboxanes. Two isoforms, COX-1 and COX-2, are constitutively expressed in peripheral tissues and in the central nervous... 

NSAIDS and a Statin . Benzene rings provide the aromatic nucleus for the majority of the NSAIDs. A propionic acid attached at its 2 position provides the side chain for most of these compounds, as noted in Chapter 2. Inhibition of the cyclooxygenase enzyme and consequently NSAID activity is retained when the role of an aromatic ring is filled by a pyrrole. The side chain for all but one of those compounds, it should be noted, consists of an otherwise unsubstituted acetic acid. 

NSAID-Assodated Ulcer. NSAIDs inhibit the production of prostaglandins, prostacyclins, and thromboxanes from arachidonic acid by covalently modifying the enzyme cyclooxygenase (COX) and irreversibly inhibiting the ability of arachidonic acid to bind to the active site on the enzyme. Chronic administration of NSAIDs has been linked to ulcer disease, although there is no evidence that they are the direct cause of ulcer formation. In patients already diagnosed with ulcer disease, chronic administration of NSAIDs was associated with a fourfold increase in the risk of ul-... 

Aspirin and NSAID suppress prostaglandin production by inhibiting cyclooxygenase enzymes. Renal blood flow, particularly within the renal medulla, is highly dependent upon systemic and local production of vasodilatory prostaglandins. 

B. Mechanism of Action Aspirin and other NSAIDs inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase. Thromboxane is a potent stimulator of platelet aggregation. Aspirin is particularly effective because it irreversibly inactivates the enzyme. Because the platelet lacks the machinery for synthesis of new protein, inhibition by aspirin persists until new platelets are formed (several days). Other NSAIDs cause a less persistent antiplatelet effect (hours). 

NSAIDs mechanism of action relays inhibition of production of prostanoids to prevent the inflammatory pain. Two cyclooxygenase enzymes contribute to the conversion of arachidonic acid to prostaglandin H2 cyclooxygenase-1 (COX-1) is a constitutive form of cyclooxygenase but COX-2 tends to be induced primarily by inflammation in most tissues. Many recent medications and investigations are directed at inhibiting COX-2 to relieve pain, such as celecoxib. 

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