Prostaglandin nonsteroidal anti-inflammatory drugs

Pharmacotherapy. Acute relief of inflammatory symptoms can be achieved by prostaglandin synthase inhibitors nonsteroidal anti-inflammatory drugs, or NSAlDs, such as diclofenac, indomethacin, piroxicam, p. 200), and glucocorticoids (p. 248). The inevitably chronic use of NSAlDs is likely to cause adverse effects. Neither NSAlDs nor glucocorticoids can halt the progressive destruction of joints. 

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat the signs and symptoms of inflammation, particularly arthritic pain. - It is mainly through the inhibition of cyclooxygenases (COXs), key enzymes in prostaglandin (PG) biosynthesis from arachidonic acid, that NSAIDs exert their anti-inflammatory effect. 

Hypersensitivity to salicylates or nonsteroidal anti-inflammatory drugs (NSAIDs). Use extreme caution in patients with history of adverse reactions to salicylates. Cross-sensitivity may exist between aspirin and other NSAIDs that inhibit prostaglandin synthesis, and aspirin, and tartrazine. Aspirin cross-sensitivity does not appear to occur with sodium salicylate, salicylamide, or choline salicylate. Aspirin hypersensitivity is more prevalent in those with asthma, nasal polyposis, chronic urticaria. 

Pharmacology Nonsteroidal anti-inflammatory drugs have analgesic, antipyretic, and anti-inflammatory activities. Major mechanism is believed to be inhibition of cyclooxygenase activity and prostaglandin synthesis. 

A.N. Hata, T.P. Lybrand, L.J. Marnett, R.M. Breyer, Structural determinants of aryla-cetic acid nonsteroidal anti-inflammatory drugs necessary for binding and activation of the prostaglandin D2 receptor CRTH2, Mol. Pharmacol. 67 (2005) 640. 

Mecfianism of Action-. A nonsteroidal anti-inflammatory drug (NSAID) that inhibits prostaglandin synthesis by inhibiting cyclooxygenase 1 and cyclooxygenase 2. Therapeutic Effect Produces anti-inflammatory effect. 

Figure 8.9 Prostaglandins and leukotrienes are potent eicosanoid lipid mediators, derived from phospholipase-released arachidonic acids, that are involved in numerous homeostatic biological functions and inflammation. They are generated by cyclooxygenase isozymes and 5-lipoxygenase, respectively, and their biosynthesis and pharmacological actions are inhibited by clinically relevant nonsteroidal anti-inflammatory drugs.

Important drug interactions include those with potassium supplements or potassium-sparing diuretics, which can result in hyperkalemia. Nonsteroidal anti-inflammatory drugs may impair the hypotensive effects of ACE inhibitors by blocking bradykinin-mediated vasodilation, which is at least in part, prostaglandin mediated. 

Renal clearance of lithium is reduced about 25% by diuretics (eg, thiazides), and doses may need to be reduced by a similar amount. A similar reduction in lithium clearance has been noted with several of the newer nonsteroidal anti-inflammatory drugs that block synthesis of prostaglandins. This interaction has not been reported for either aspirin or acetaminophen. All neuroleptics tested to date, with the possible exception of clozapine and the newer atypical antipsychotics, may produce more severe extrapyramidal syndromes when combined with lithium. 

Nonsteroidal anti-inflammatory drugs [P] Indomethacin reduces antihypertensive response other prostaglandin inhibitors probably also interact. 

Patrignani, P., Panara, M. R., Sciulli, M. G., Santini, G., Renda, G., Patrono, C. Differential inhibition of human prostaglandin endoperoxide synthase-1 and -2 by nonsteroidal anti-inflammatory drugs, J. Physiol. Pharmacol. 1997, 48, 623-631. 

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