NSAIDs不良反应PPT.ppt

The potentially important pharmacologic differences between celecoxib and rofecoxib are related to chemical structure, oral bioavailability, half-life, and main pathways of hepatic metabolism. Whereas rofecoxib contains a sulfone side chain, celecoxib has a sulfonamide. This is a clinically significant difference as celecoxib is contraindicated in patients with a history of allergic reaction to sulfonamides. Rofecoxib has a significantly higher oral bioavailability compared with celecoxib (90% vs 22%–40%, respectively). Celebrex? (celecoxib). US prescribing information. G.D. Searle Co. 2000. FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med. 2001;345:433-442. Vioxx? (rofecoxib). US product information. Merck Co., Inc. 2000. 与NSAIDs一样，COX-2抑制剂也能够升高某些患者的血压，引起 心血管不了反应。因此，在开处方时，需要提醒患者，尤其对高危 患者（如老年和脱水患者）注意该不良作用。 ——Hui-Fang Cheng, Raymond C. Harris.Hypertension. 2004;43:525-530 The safety profiles of the COX-2–specific inhibitors have been compared with those of traditional NSAIDs and placebo. The 2 cyclooxygenase isoforms, COX-1 and COX-2, are main players in the formation of PGs from arachidonic acid. PGs are produced constitutively in many tissues in the body, including the brain, GI tract, and kidneys, and their synthesis is also induced at sites of inflammation. In the kidneys, PGs act as modulators of physiologic functions such as microvascular hemodynamics, tubular salt and water reabsorption, and renin release. The most important PGs in the kidneys are PGE2 and PGI2 (prostacyclin). PGE2 decreases tubular Na+ reabsorption. PGI2 stimulates renin release, which in turn stimulates secretion of aldosterone, and further leads to an increased K+ secretion at the distal nephron. PGI2 is also a potent vasodilator that preserves renal perfusion in conditions associated with decreased actual or effective circulating volume. Brater DC. Effects of nonsteroidal anti-inflammatory drugs on renal function: focus