NSAIDs eicosanoids

See also Prostaglandin Biosynthesis, NSAIDs, Eicosanoid Functions... 

Patients with chronic idiopathic urticaria, who develop cutaneous reactions in response to aspirin, display certain similarities in eicosanoid profile with AIA. The mechanism of the reactions is often related to COX-1 inhibition [18]. Therefore, aspirin and all drugs that inhibit COX-1 should be avoided in patients who already have had cutaneous reactions to NSAID. Coxibs are usually well tolerated, although occasional adverse reactions have been reported [19, 20]. For treatment of the reactions, antihistamines are usually sufficient, but in more severe cases adrenaline and corticosteroids may be warranted. 

Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase [2] and consequently the synthesis of most eicosanoids. This explains their analgesic, antipyretic, and antirheumatic effects. Frequent side effects of NSAIDs also result from inhibition of eicosanoid synthesis. For example, they impair hemostasis because the synthesis of thromboxanes by thrombocytes is inhibited. In the stomach, NSAIDs increase HCl secretion and at the same time inhibit the formation of protective mucus. Long-term NSAID use can therefore damage the gastric mucosa. 

Common NSAIDs include aspirin, ibuprofen, indomethacin, naproxen, and ketoprofen. Even though anti-inflammatories generally target cyclooxygenase, there are apparent differences in the details of how they relieve pain. For example, aspirin acts by primarily inhibiting the COX-dependent synthesis of eicosanoids, which are end products of metabolism of essential fatty acids including prostaglandin... 

The relationship of eicosanoids to infection is not well defined. The association between the use of the anti-inflammatory steroids and increased risk of infection is well established. However, NSAIDs do not seem to alter patient responses to infection. 

Studying the biosynthesis of eicosanoids has led to other discoveries as well. For example, aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) inactivate the cyclooxygenase enzyme needed for prostaglandin synthesis. In this way, NSAIDs block the synthesis of the prostaglandins that cause inflammation (Section 19.6). 

Figure 14.1 Pathway of formation of eicosanoid mediators following cellular injury, NSAID, non-steroidal anti-inflammatory drug.

The anti-inflammatory mechanism of the NSAIDs is principally related to any or all of the following three factors the inhibition of different enzymes implicated in the arachidonic acid metabolism, the modification of the effects of relevant mediators, and the inhibition of the tissue damage produced by free radicals. It is thought that the phenomenon of overexpression of the enzymes implicated in inflammation may be avoided by the effect of apoptotic mechanisms on inflammatory cells. The role of eicosanoids and NSAIDs, with either a positive or negative... 

PGE2 and PGF2CI stimulate synthesis of protective mucus in stomach and in small intestine. When ASA is administrated, prostaglandins and prostacyclins synthesis is blocked and acid secretion is increased, reducing mucosae protection. COX has two different isoforms COX-1, expressed in most tissues and implicated in the regulation of normal homeostatic functions such as gastric acid secretion and COX-2, induced often by inflammatory processes. As a result, COX-2 is implicated in the production of pro-inflammatory eicosanoids (see Figure 25). In feet, one of the therapeutic actions of ASA et similia NSAIDs has been the inhibition of COX activity to reduce pro-inflammatory eicosanoids [73]. 

See also Eicosanoids, Prostaglandin Biosynthesis, Prostaglandins, l-feC Thromboxanes, NSAIDS ... 

INFLAMMATION AND IMMUNITY Eicosanoids play a major role in the inflammatory and immune responses, as reflected by the clinical usefulness of the NSAIDs. While LTs generally are proinflammatory and Upoxins anti-inflammatory, prostanoids can exert both kinds of activity. 

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