Part 5 Antiatheroscleotic drugs
Normal bood cap of plaque B Loid.chore of pLague Endotenon C Atherosclerosis is a disorder in which lipid deposits accumulate on the lining of the blood vessels, eventually producing degenerative changes and obstruction of blood flow. Atherosclerosis is considered to be a major contributor in the development of heart disease
Plasma lipids Cholesterol free cholesterol(fo cholesterylester(ce) Triglyceride(tg) Phospholipid (Pl) Plasma lipoproteins Apoprotein(apo) ipoprotein(apoprotein+ lipids) Chylomicron(CM) Very low density lipoprotein (VLDL) Low density lipoprotein (LDL) Intermediate density lipoprotein (IDL) High density lipoprotein(HDL)
Dietary fat cholesterol - Chylomicrons LPL、 Chylomicron remnants INTESTINE FFA Adipose LPL tissue HL Bile acids FFA Peripheral tissues (with LDI receptors FFA ∵∵∵:了 LPL VLD IDL LDL LIVER receptors' i HL 的: Remnant, ApoE mediated 它: receptors ApoB mediated A poE mediated Lipid metabolism in the body
Drugs used in treatment of atherosclersis 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) a 4. Protective agents for arterial endothelium(动脉内皮保护药)
Drugs used in treatment of atherosclersis a Lipid-regulators HMG COA reductase inhibitors(statins ) lovastatin(洛伐他汀),etc. Inhibitors of intestinal sterol absorption Bile acid binding resins(胆酸结合树脂) colestyramine(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) gemfibrozil(吉非贝齐), benzafibrate(苯扎贝特,etc
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Drugs used in treatment of atherosclersis MG 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
MEVASTATIN LOVASTATIN SIMVASTATIN PRAVASTAT OH HIC 小人hC CH3 H3C CH3 CH3 H3C 'H CH H3C FLUVASTATIN ATORVASTATIN CERIVASTATIN CH3)2CH ①叉叉∞m CH(CI H3)2 Hco 2 (CH3)2HC CH(CH3) Reaction Catalyzed by HMG-CoA Reductase HMG COA HO CH3 CO0 NADPH +H COo NADPH+H Fcoo- reductase inhibitors HMG-COA Intermediate Mevalonate
Drugs used in treatment of atherosclersis 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
Hepatocyte Golgi endothelium vesicle B-100 LO RER A Lipoprotein lipase ApoB VLDL ApoE Apoc VLDL ● Cholesterol LDL receptor remnant Lysosome FFA Mevalonic HDL acid HMG-COA LDL reductase A Peripheral cell 口CoA Cholesterol biosynthetic Cholesterol pathway Lysosome Cholesteryl esters