PHAR 340 Lecture Notes - Lecture 27: Vascular Smooth Muscle, Cytochrome C Oxidase Subunit Ii, Annexin
23 Dec 2018
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Release of aa by phospholipase is the rate limiting step. Drugs that target this are not useful bc there are several effects and are severe. Inhibit biosyn glucocorticoids: stim syn of lipocortin which inhibits phospholipase decr aa. + eicosanoids for chemotaxis/inflam (see aa release) but have toxic actions. Nsaids: inhibits cox and decr formation of pg endoperoxides (inhibit at start of pathway), includes indomethacin, naproxen + ibuprofen (all inhibit cox irrev or rev), efficacy parallels cox inhibition. Asa acetylates serine in active site (irrev) and metabolite (salicylic acid) inhibits pg formation in vivo reversibly. Lox inhibitor: zileuton a 5-lox inhibitor for asthma that"s less effective than steroids and causes hepatotoxicity via ddis (cyp3a4) Flap inhibitors: flap needed for 5-lox activity, in clinical trials. Txa2 inhibition: want to decr tx (stim platelet aggregation) syn w/out decr pgi2 (vasodilator, inhibits aggregation) Cox1 vs cox2 thought cox-1 was only in non-inflam cells and cox2 in inflame cells, most nsaids are not selective.
