β受体阻滞剂的的基因多态性20110416资料.ppt

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β受体阻滞剂的的基因多态性20110416资料.ppt

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β受体阻滞剂的的基因多态性20110416资料

美托洛尔受2D6基因多态性影响显著━IM,PM患者极易中毒美托洛尔70%经2D6代谢. Clin Pharmacol Ther 2005;78:378-87 美托洛尔在三组患者的疗效比较 2D6等位基因中国汉族的分布 The Pharmacogenomics Journal 2009:9;380–394 Four major alleles of CYP2D6 (*1, *2, *5 and *10) vary significantly (P0.05) 美托洛尔受2D6基因多态性影响显著 Pharmacotherapy 2007;27:874~887 美托洛尔等增加PM患者心动过缓的风险 leading to an increased risk of bradycardia in PM s odds ratio = 3.86(95% confidence interval 1.68–8.86) ;P = 0.0014 Clinical pharmacology Therapeutics 2009 ; 85 FDA推荐用前进行基因多态性检测的药品 chemical name for bisoprolol fumarate is (±)-1-[4-[[2-(1-Methylethoxy)ethoxy] methyl]phenoxy]-3-[(1-methylethyl)amino]-2-propanol(E)-2-butenedioate 富马酸比索洛尔 (Bisoprolol fumarate;康忻) 最常用三种β-受体阻滞剂的比较 25% 38% β1/β2 120 7 75 比索洛尔的作用特点 Bisoprolol has a higher degree of β1-selectivity (cardioselective) compared to other β1-selective β-blockers such as atenolol, metoprolol and betaxolol, Bisoprolol has a stronger antihypertensive effect and cardioprotective ; Bisoprolol inhibits renin secretion by about 65% and tachycardia by about 35%; In animal testing bisoprolol compared to propranolol has shown less sedative effects and only slightly reduced glucose tolerance. Diarrhea; dizziness; drowsiness; fatigue; headache; lightheadedness; nausea; sleeplessness; unusual tiredness; weakness. ?-Blockers Differ in Their Long-Term Effects on Mortality in HF Bisoprolol1 Bucindolol2 Carvedilol3-5 Metoprolol tartrate6 Metoprolol succinate7 Nebivolol8 Xamoterol9 Beneficial No effect Beneficial No effect Beneficial No effect Harmful 1CIBIS II Investigators and Committees. Lancet. 1999;353:9-13. 2The BEST Investigators. N Engl J Med 2001; 344:1659-1667. 3Colucci WS, et al. Circulation 1996;94:2800-2806. 4Packer M, et al. N Engl J Med 2001;344:1651-1658. 5The CAPRICORN Investigators. Lancet. 2001;357:1385-1390. 6Waagstein F, et al. Lancet. 1993;342:1441-1446. 7MERIT-HF Study Group. Lancet. 1999;353:2001-2007. 8SENIORS Study Group. Eur Heart J. 2005; 26:215-225. 9The Xamoterol in Sever