Part 5Part 5

Antiatheroscleotic drugs Antiatheroscleotic drugs

Plasma lipidsPlasma lipids Cholesterol Cholesterol free cholesterol (FC)free cholesterol (FC) cholesterolester (CE)cholesterolester (CE) Triglyceride (TG)Triglyceride (TG) Phospholipid (PL)Phospholipid (PL)

Plasma lipoproteinsPlasma lipoproteins Apoprotein (apo)Apoprotein (apo) Lipoprotein (Lipoprotein (apoprotein + lipidsapoprotein + lipids)) Chylomicron (CM)Chylomicron (CM) Very low density lipoprotein (VLDL)Very low density lipoprotein (VLDL) Low density lipoprotein (LDL)Low density lipoprotein (LDL) Intermediate density lipoprotein (IDL)Intermediate density lipoprotein (IDL) High density lipoprotein (HDL)High density lipoprotein (HDL)

Lipid metabolism in the bodyLipid metabolism in the body

Drugs used in treatment of atheroscleosisDrugs used in treatment of atheroscleosis

1.1. Lipid-regulatorsLipid-regulators （（调血脂药调血脂药））2. Antioxidants2. Antioxidants （（抗氧化药抗氧化药））3. Polyunsaturated fatty acids 3. Polyunsaturated fatty acids (PUFAs) (PUFAs) （（多不饱和脂肪酸多不饱和脂肪酸））4. Protective agents for arterial4. Protective agents for arterial endotheliumendothelium （（动脉内皮保护药动脉内皮保护药））

Drugs used in treatment of atheroscleosisDrugs used in treatment of atheroscleosis

Lipid-regulatorsLipid-regulators HMG CoA reductase inhibitors (HMG CoA reductase inhibitors (statinsstatins):): lovastatinlovastatin （洛伐他汀）（洛伐他汀） , , etc. etc. Inhibitors of intestinal sterol absorption:Inhibitors of intestinal sterol absorption: Bile acid binding resinsBile acid binding resins ( ( 胆酸结合树脂胆酸结合树脂 ):): colestryraminecolestryramine （考来烯胺）（考来烯胺） , colestipol, colestipol （考来替泊）（考来替泊） Inhibitor of cholesterol absorption: ezetimibe Inhibitor of cholesterol absorption: ezetimibe ((依泽替米依泽替米贝贝 ))

Nicotinic acids (Nicotinic acids ( 烟酸类烟酸类 ):): nicotinic acidnicotinic acid （烟酸）（烟酸） , acipimox , acipimox （阿西莫司）（阿西莫司） Fibric acids (Fibric acids ( 贝特类，苯氧酸类贝特类，苯氧酸类 ):): gimfibrozilgimfibrozil （吉非贝齐）（吉非贝齐） , benzafibrate, benzafibrate ( (苯扎贝特苯扎贝特 )), , etcetc..

Drugs used in treatment of atheroscleosisDrugs used in treatment of atheroscleosis

HMG CoA reductase inhibitorsHMG CoA reductase inhibitors （（ HMG CoAHMG CoA: 3-hydroxy-3-menthylglutaryl-coenzyme A, : 3-hydroxy-3-menthylglutaryl-coenzyme A, 3-3- 羟基羟基 -3--3- 甲甲

基基 -- 戊二酸单酰辅酶戊二酸单酰辅酶 AA ））

Lovastatin Lovastatin 洛伐他汀洛伐他汀 Simvastatin Simvastatin 辛伐他汀辛伐他汀 Pravastatin Pravastatin 普伐他汀普伐他汀 Fluvastatin Fluvastatin 氟伐他汀氟伐他汀 Mevastatin Mevastatin 美伐他汀美伐他汀 Atorvastatin Atorvastatin 阿伐他汀阿伐他汀 Cerivastatin Cerivastatin 西立伐他汀西立伐他汀

HMG CoA HMG CoA reductase ireductase inhibitorsnhibitors

Drugs used in treatment of atheroscleosisDrugs used in treatment of atheroscleosis

HMG CoA reductase inhibitorsHMG CoA reductase inhibitors

1.1. Pharmacological effects Pharmacological effects

(1) Reducing plasma LDL and total cholesterol (1) Reducing plasma LDL and total cholesterol levelslevels

inhibiting atherosclerosis formationinhibiting atherosclerosis formation (2) Other effects: (2) Other effects: inhibiting hypertrophy of arterial smooth inhibiting hypertrophy of arterial smooth

muscles, inflammation, free radicals muscles, inflammation, free radicals protecting vascular endotheliumprotecting vascular endothelium

Action of HMG CoA reAction of HMG CoA reductase inhibitors on chductase inhibitors on cholesterol biosynthesisolesterol biosynthesis

Actions of HMG CoA reductase inhibitActions of HMG CoA reductase inhibitors on cholesterol biosynthesisors on cholesterol biosynthesis

Lipid-lowing effectLipid-lowing effect

Other effects via Other effects via modulating signal modulating signal transductiontransduction

甲羟戊酸甲羟戊酸

鲨烯鲨烯

类异戊二烯类异戊二烯

Drugs used in treatment of atheroscleosisDrugs used in treatment of atheroscleosis

2.2. Clinical uses Clinical uses

Treatment of hypercholesterolemia: Treatment of hypercholesterolemia: prevention oprevention of cardiovascular and cerebrovascular diseasesf cardiovascular and cerebrovascular diseases

Other diseasesOther diseases

3.3. Adverse effects Adverse effects GI reactionsGI reactions HepatotoxicityHepatotoxicity MyopathyMyopathy

Drugs used in treatment of atheroscleosisDrugs used in treatment of atheroscleosis

Inhibitors of intestinal sterol absorption:Inhibitors of intestinal sterol absorption:Bile acid binding resinsBile acid binding resins ( ( 胆酸结合树脂胆酸结合树脂 ):): colestryraminecolestryramine （（考来烯胺考来烯胺）） , colestipol, colestipol （（考来替泊考来替泊）） bile acid bile acid cholesterol cholesterolbile acid bile acid LDL-C LDL-C Combined with statinsCombined with statins GI reactions; plasma TG GI reactions; plasma TG ; liposoluble vitamin absorption ; liposoluble vitamin absorption

Inhibitor of cholesterol absorption: Inhibitor of cholesterol absorption: ezetimibe ezetimibe ((依泽替米依泽替米贝贝 ))

a selective inhibitor of intestinal absorption of cholesterol and phytosteroa selective inhibitor of intestinal absorption of cholesterol and phytosterolsls

high tolerancehigh tolerance

Actions of intestinal Actions of intestinal sterol absorption sterol absorption inhibitors inhibitors

Drugs used in treatment of atheroscleosisDrugs used in treatment of atheroscleosis

Nicotinic acids (Nicotinic acids ( 烟酸类烟酸类 ):): nicotinic acidnicotinic acid （烟酸）（烟酸） , acipimox , acipimox （阿西莫司）（阿西莫司）

Inhibiting degradation of TG, reducing free fatty acid and hInhibiting degradation of TG, reducing free fatty acid and hepatic synthesis of TGepatic synthesis of TG

Reducing VLDL and LDL through TG synthesis reductionReducing VLDL and LDL through TG synthesis reduction

Increasing LPL activity, accelerating clearance of TG in CIncreasing LPL activity, accelerating clearance of TG in CM and VLDL M and VLDL

Adjuvant treatment of statinsAdjuvant treatment of statins

Action of nicotinic Action of nicotinic acids acids

Drugs used in treatment of atheroscleosisDrugs used in treatment of atheroscleosis

Fibric acids (Fibric acids ( 贝特类，苯氧酸类贝特类，苯氧酸类 ):): gimfibrozilgimfibrozil （吉非贝齐）（吉非贝齐） , benzafibrate, benzafibrate ( (苯扎贝特苯扎贝特 )), , etcetc..

as ligands for the nuclear transcription receptor, PPAR-as ligands for the nuclear transcription receptor, PPAR-;; transcriptionally up-regulating LPL, apoA-I and apoA-II; down regulattranscriptionally up-regulating LPL, apoA-I and apoA-II; down regulat

ing apoCIII, an inhibitor of lipolysis. ing apoCIII, an inhibitor of lipolysis.

increasing oxidation of fatty acids in liver and striated muscleincreasing oxidation of fatty acids in liver and striated muscle increasing lipolysis of lipoprotein triglyceride via LPLincreasing lipolysis of lipoprotein triglyceride via LPL decreasing intracellular lipolysis in adipose tissue and VLDL levels, in pdecreasing intracellular lipolysis in adipose tissue and VLDL levels, in p

art as a result of decreased secretion by the liverart as a result of decreased secretion by the liver

Only modest reductions of LDL occur in most patients. In others, especiOnly modest reductions of LDL occur in most patients. In others, especially those with combined hyperlipidemia, LDL often increases as triglycally those with combined hyperlipidemia, LDL often increases as triglycerides are reduced.erides are reduced.

Hepatic and peripheral effects of fibratesHepatic and peripheral effects of fibrates LPL: lipoprotein lipase; VLDL: very-low-density lipoproteinsLPL: lipoprotein lipase; VLDL: very-low-density lipoproteins

Drugs used in treatment of atheroscleosisDrugs used in treatment of atheroscleosis

Antioxidants: Antioxidants: probucolprobucol （普罗布考）（普罗布考） , vitamin E, vitamin E Inhibiting ox-LDL formationInhibiting ox-LDL formation

Polyenoic acidsPolyenoic acids ( ( 多烯脂肪酸类多烯脂肪酸类 ))

Protective agents for arterial endotheliuProtective agents for arterial endothelium: m: polysaccharide sulfatepolysaccharide sulfate （硫酸多糖）（硫酸多糖）