Part 5 Antiatheroscleotic drugs

§Plasma lipids § Cholesterol free cholesterol (FC) § cholesterolester (CE) § Triglyceride (TG) § Phospholipid (PL) §Plasma lipoproteins § Apoprotein (apo) § Lipoprotein (apoprotein + lipids) § Chylomicron (CM) § Very low density lipoprotein (VLDL) § Low density lipoprotein (LDL) § Intermediate density lipoprotein (IDL) § High density lipoprotein (HDL)

Lipid metabolism in the body

Drugs used in treatment of atheroscleosis §1. Lipid-regulators （ 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-regulators § HMG CoA reductase inhibitors ( statins ): § lovastatin （洛伐他汀）, etc. Inhibitors of intestinal sterol absorption: § 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: ezetimibe ( 依泽替米贝 ) § Nicotinic acids ( 烟酸类 ): § nicotinic acid （烟酸）, acipimox （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 ） § Lovastatin 洛伐他汀 § Simvastatin 辛伐他汀 § Pravastatin 普伐他汀 § Fluvastatin 氟伐他汀 § Mevastatin 美伐他汀 § Atorvastatin 阿伐他汀 § Cerivastatin 西立伐他汀

§HMG CoA reductase inhibitors

Drugs used in treatment of atheroscleosis §HMG CoA reductase inhibitors §1. Pharmacological effects §(1) Reducing plasma LDL and total cholesterol levels § inhibiting atherosclerosis formation §(2) Other effects: § inhibiting hypertrophy of arterial smooth muscles, inflammation, free radicals § protecting vascular endothelium

Action of HMG CoA reductase inhibitors on cholesterol biosynthesis

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 of atheroscleosis §2. Clinical uses §Treatment of hypercholesterolemia: prevention of cardiovascular and cerebrovascular diseases §Other diseases §3. Adverse effects § GI reactions § Hepatotoxicity § Myopathy

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   cholesterol  bile acid   LDL-C  § Combined 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

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） §Inhibiting degradation of TG, reducing free fatty acid and hepatic synthesis of TG §Reducing VLDL and LDL through TG synthesis reduction §Increasing LPL activity, accelerating clearance of TG in CM and VLDL §Adjuvant treatment of statins

Action of nicotinic acids

Drugs used in treatment of atheroscleosis §Fibric acids ( 贝特类，苯氧酸类 ): § gimfibrozil （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 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, 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 LPL: lipoprotein lipase; VLDL: very-low-density lipoproteins

Drugs used in treatment of atheroscleosis §Antioxidants: probucol （普罗布考）, vitamin E § Inhibiting ox-LDL formation §Polyenoic acids ( 多烯脂肪酸类 ) §Protective agents for arterial endothelium: polysaccharide sulfate （硫酸多糖）