英文医学课件：22 抗动脉粥样硬化药

1、Part 5 Antiatheroscleotic drugs抗动脉粥样硬化药,动脉粥样硬化,Plasma lipids 血脂 Cholesterol free cholesterol (FC) 游离胆固醇 cholesterolester (CE) 胆固醇酯 Triglyceride (TG) 甘油三脂 Phospholipid (PL) 磷脂 Plasma lipoproteins 血浆脂蛋白 Apoprotein (apo) 载脂蛋白 Lipoprotein (apoprotein + lipids) 脂蛋白 Chylomicron (CM) 乳糜微粒 Very low density

2、lipoprotein (VLDL) 极低密度脂蛋白 Low density lipoprotein (LDL) 低密度脂蛋白 Intermediate density lipoprotein (IDL) 中间密度脂蛋白 High density lipoprotein (HDL) 高密度脂蛋白,Lipid metabolism in the body 体内脂质代谢,endogenous,FFA: free fatty acid; LPL: lipoprotein lipase; HL: hepatic lipase,exogenous,Lipid metabolism in the body

3、 体内脂质代谢,exogenous,endogenous,Drugs used in treatment of atheroscleosis,1. Lipid-regulating drugs（调血脂药） 2. Antioxidants（抗氧化药） 3. Polyunsaturated fatty acids (PUFAs) （多不饱和脂肪酸） 4. Protective agents for arterial endothelium（动脉内皮保护药）,Drugs used in treatment of atheroscleosis,Lipid-regulating drugs 调脂药物 H

4、MG CoA reductase inhibitors (statins, 他汀类): lovastatin（洛伐他汀）, etc. Inhibitors of intestinal sterol absorption: Bile acid binding resins (胆酸结合树脂): colestryramine（考来烯胺）, colestipol（考来替泊） Inhibitor of cholesterol absorption (抑制胆固醇吸收): ezetimibe (依泽替米贝) Nicotinic acids (烟酸类): nicotinic acid（烟酸）, acipimo

5、x （阿西莫司） Fibric acids (贝特类，苯氧酸类): gimfibrozil（吉非贝齐）, benzafibrate (苯扎贝特), etc.,Drugs used in treatment of atheroscleosis,HMG CoA reductase inhibitors （HMG CoA: 3-hydroxy-3-menthylglutaryl-coenzyme A, 3-羟基-3-甲基-戊二酸单酰辅酶A, 羟甲基戊二酸单酰辅酶A） Lovastatin 洛伐他汀 Simvastatin 辛伐他汀 Pravastatin 普伐他汀 Fluvastatin 氟伐他汀

6、Mevastatin 美伐他汀 Atorvastatin 阿伐他汀 Cerivastatin 西立伐他汀,HMG CoA reductase inhibitors,甲羟戊酸,Drugs used in treatment of atheroscleosis,HMG CoA reductase inhibitors 1. Pharmacological effects 药理作用 (1) Reducing plasma LDL and total cholesterol levels 降低血浆LDL和总胆固醇 inhibiting atherosclerosis formation increas

7、ing LDL receptor 抑制动脉粥样硬化形成，增加LDL受体,甲羟戊酸,Action of HMG CoA reductase inhibitors on cholesterol biosynthesis 羟甲基戊二酸单酰辅酶A抑制药对胆固醇合成的作用,Action of HMG CoA reductase inhibitors on cholesterol biosynthesis 羟甲基戊二酸单酰辅酶A抑制药对胆固醇合成的作用,甲羟戊酸,Drugs used in treatment of atheroscleosis,(2) Other effects: inhibiting

8、hypertrophy of arterial smooth muscles, inflammation, free radicals 抑制动脉平滑肌增殖、炎症、自由基生成 protecting vascular endothelium 保护血管内皮,Actions of HMG CoA reductase inhibitors on cholesterol biosynthesis,Lipid-lowing effect,Other effects via modulating signal transduction,甲羟戊酸,鲨烯,类异戊二烯,Drugs used in treatment

9、 of atheroscleosis,2. Clinical uses 临床应用 Treatment of hypercholesterolemia 高胆固醇血症: primary and secondary prevention of cardiovascular and cerebrovascular diseases Other diseases 其他疾病 3. Adverse effects 不良反应 GI reactions 胃肠道反应 Hepatotoxicity 肝毒性 Myopathy 肌病,阿伐他汀对脑卒中的一级和二级预防作用,一级预防,二级预防,辛伐他汀对脑卒中类型和严重度

10、的影响（Meta分析）,辛伐他汀对脑卒中随访的结果综合（Meta分析）,0.75 (0.66-0.85) P0.0001,辛伐他汀,普伐他汀,阿伐他汀,他汀类药物对脑卒中的长期疗效,辛伐他汀和阿伐他汀对5年随访中脑卒中发生率的影响,辛伐他汀,阿伐他汀,Drugs used in treatment of atheroscleosis,Inhibitors of intestinal sterol absorption: Bile acid binding resins (胆酸结合树脂): colestryramine（考来烯胺）, colestipol（考来替泊） bile acid chol

11、esterol bile acid LDL-C Combined use with statins GI reactions; plasma TG ; liposoluble vitamin absorption Inhibitor of cholesterol absorption: ezetimibe (依泽替米贝) a selective inhibitor of intestinal absorption of cholesterol and phytosterols high tolerance; excreting from milk (contraindicated in lac

12、tation woman),Actions of intestinal sterol absorption inhibitors,Actions of intestinal sterol absorption inhibitors,Drugs used in treatment of atheroscleosis,Nicotinic acids (烟酸类): nicotinic acid（烟酸）, acipimox （阿西莫司） 降低甘油三酯 Inhibiting degradation of TG, reducing free fatty acid and hepatic synthesis

13、 of TG Reducing VLDL and LDL through reducing TG synthesis Increasing LPL activity, accelerating clearance of TG in CM and VLDL Face flashing 潮红, GI reactions胃肠道反应;contraindicated in diabetes, ulcers, active hepatic disease, pregnant woman 禁用于糖尿病、溃疡病、急性肝病、孕妇 Adjuvant treatment of statins 他汀类药物辅助用药,A

14、ction of nicotinic acids 烟酸作用示意图,Drugs used in treatment of atheroscleosis,Fibric acids (贝特类，苯氧酸类): gemfibrozil（吉非贝齐）, benzafibrate (苯扎贝特), etc. as ligands for the nuclear transcription receptor, PPAR-; transcriptionally up-regulating LPL, apoA-I and apoA-II; down-regulating apoCIII (an inhibitor of

15、 lipolysis). increasing oxidation of fatty acids in liver and striated muscle increasing lipolysis of lipoprotein triglyceride via LPL decreasing intracellular lipolysis in adipose tissue and VLDL levels (降低VLDL), in part as a result of decreased secretion by the liver Only modest reductions of LDL occur in most patients. In others, especially those with combined hyperlipidemia, LDL often increases as triglycerides are reduced.,Hepatic and peripheral effects of fibrates 贝特类药物作用环节 LPL: lipoprotein lipase; VLDL: very-low-density lipoproteins,Hepatic and peripheral effects of fibrates 贝特类药物作用