NSAIDs和痛风药(吴柯).pptVIP

* 花生四烯酸 PGI2 PGE2 减少 Na+ 重吸收 Brater. Am J Med. 1999;107:65S. 刺激肾素释放 ? 醛固酮分泌 ? K+ 分泌 血管舒张 - GFR - 肾血流量 COX-1, COX-2 GFR = glomerular filtration rate. 6.肾功能损害 * NSAIDs 对肾功能的影响 Brater. Am J Med. 1999;107:65S. CHF = congestive heart failure. PGI2 高钾血症 急性肾衰 PGE2 钠潴留 外周性水肿 ? 血压 ? 体重 CHF (rarely) 花生四烯酸 COX-1 COX-2 NSAIDs * 禁忌症 胃溃疡、 严重肝损伤、 低凝血酶原血症、 维生素K缺乏症、 血友病、 哮喘、 鼻息肉、 俄 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 on cyclooxygenase-2-selective inhibition. Am J Med. 1999;107:65S-71S. PGE2 decreases Na+ reabsorption at the cortical thick ascending limb of the loop of Henle. Thus, COX inhibition by NSAIDs leads to increased Na+ reabsorption, decreased response to diuretics (15%–20%), weight gain, occasional edema, and potentially CHF. NSAIDs can also decrease the response to antihypertensive agents and thus cause an increase in blood pressure (BP) (≤5 mmHg). PGI2 stimulates renin release and ultimately leads to an increase of K+ secretion by the distal nephron. Therapy with NSAIDs results in a hyporeninemic hypoaldosteronism that clinically manifests as type IV renal tubular acidosis and hyperk