医学教学课件：抗动脉粥样硬化药

Part5

Antiatheroscleoticdrugs

抗动脉粥样硬化药动脉粥样硬化Plasmalipids血脂

Cholesterol

freecholesterol(FC)游离胆固醇

cholesterolester(CE)胆固醇酯

Triglyceride(TG)甘油三脂

Phospholipid(PL)磷脂Plasmalipoproteins血浆脂蛋白

Apoprotein(apo)载脂蛋白

Lipoprotein(apoprotein+lipids)脂蛋白

Chylomicron(CM)乳糜微粒

Verylowdensitylipoprotein(VLDL)极低密度脂蛋白

Lowdensitylipoprotein(LDL)低密度脂蛋白

Intermediatedensitylipoprotein(IDL)中间密度脂蛋白

Highdensitylipoprotein(HDL)高密度脂蛋白Lipidmetabolisminthebody体内脂质代谢endogenousFFA:freefattyacid;LPL:lipoproteinlipase;HL:hepaticlipaseexogenousLipidmetabolisminthebody

体内脂质代谢exogenousendogenousDrugsusedintreatmentofatheroscleosis1.

Lipid-regulatingdrugs（调血脂药）2.Antioxidants（抗氧化药）3.Polyunsaturatedfattyacids(PUFAs)（多不饱和脂肪酸）4.Protectiveagentsforarterialendothelium（动脉内皮保护药）DrugsusedintreatmentofatheroscleosisLipid-regulatingdrugs调脂药物

HMGCoAreductaseinhibitors(statins,他汀类):

lovastatin（洛伐他汀）,etc.

Inhibitorsofintestinalsterolabsorption:

Bileacidbindingresins(胆酸结合树脂):

colestryramine（考来烯胺）,colestipol（考来替泊）

Inhibitorofcholesterolabsorption(抑制胆固醇吸收):ezetimibe(依泽替米贝)

Nicotinicacids(烟酸类):

nicotinicacid（烟酸）,acipimox（阿西莫司）

Fibricacids(贝特类，苯氧酸类):

gimfibrozil（吉非贝齐）,benzafibrate(苯扎贝特),etc.DrugsusedintreatmentofatheroscleosisHMGCoAreductaseinhibitors（HMGCoA:3-hydroxy-3-menthylglutaryl-coenzymeA,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

Mevastatin美伐他汀

Atorvastatin阿伐他汀

Cerivastatin西立伐他汀HMGCoAreductaseinhibitors甲羟戊酸DrugsusedintreatmentofatheroscleosisHMGCoAreductaseinhibitors1.Pharmacologicaleffects药理作用(1)ReducingplasmaLDLandtotalcholesterollevels降低血浆LDL和总胆固醇

inhibitingatherosclerosisformationincreasingLDLreceptor

抑制动脉粥样硬化形成，增加LDL受体甲羟戊酸ActionofHMGCoAreductaseinhibitorsoncholesterolbiosynthesis羟甲基戊二酸单酰辅酶A抑制药对胆固醇合成的作用ActionofHMGCoAreductaseinhibitorsoncholesterolbiosynthesis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Drugsusedintreatmentofatheroscleosis(2)Othereffects:

inhibitinghypertrophyofarterialsmoothmuscles,inflammation,free

radicals抑制动脉平滑肌增殖、炎症、自由基生成

protectingvascularendothelium

保护血管内皮ActionsofHMGCoAreductaseinhibitorsoncholesterolbiosynthesisLipid-lowingeffectOthereffectsviamodulatingsignaltransduction甲羟戊酸鲨烯类异戊二烯Drugsusedintreatmentofatheroscleosis2.Clinicaluses临床应用Treatmentofhypercholesterolemia高胆固醇血症:primaryandsecondarypreventionofcardiovascularandcerebrovasculardiseasesOtherdiseases其他疾病3.Adverseeffects不良反应

GIreactions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)P<0.0001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DrugsusedintreatmentofatheroscleosisInhibitorsofintestinalsterolabsorption:Bileacidbindingresins(胆酸结合树脂):

colestryramine（考来烯胺）,colestipol（考来替泊）

bileacidcholesterolbileacidLDL-CCombinedusewithstatinsGIreactions;plasmaTG;liposolublevitaminabsorptionInhibitorofcholesterolabsorption:ezetimibe(依泽替米贝)aselectiveinhibitorofintestinalabsorptionofcholesterolandphytosterolshightolerance;excretingfrommilk(contraindicatedinlactationwoman)ActionsofintestinalsterolabsorptioninhibitorsActionsofintestinalsterolabsorptioninhibitorsDrugsusedintreatmentofatheroscleosisNicotinicacids(烟酸类):

nicotinicacid（烟酸）,acipimox（阿西莫司）降低甘油三酯InhibitingdegradationofTG,reducingfreefattyacidandhepaticsynthesisofTGReducingVLDLandLDLthroughreducingTGsynthesisIncreasingLPLactivity,acceleratingclearanceofTGinCMandVLDLFaceflashing潮红,GIreactions胃肠道反应;contraindicatedindiabetes,ulcers,activehepaticdisease,pregnantwoman禁用于糖尿病、溃疡病、急性肝病、孕妇Adjuvanttreatmentofstatins他汀类药物辅助用药Actionofnicotinicacids烟酸作用示意图DrugsusedintreatmentofatheroscleosisFibricacids(贝特类，苯氧酸类):

gemfibrozil（吉非贝齐）,benzafibrate(苯扎贝特),etc.asligandsforthenucleartranscriptionreceptor,PPAR-;transcriptionallyup-regulatingLPL,apoA-IandapoA-II;down-regulatingapoCIII(aninhibitoroflipolysis).increasingoxidationoffattyacidsinliverandstriatedmuscleincreasinglipolysisoflipoproteintriglycerideviaLPLdecreasingintracellularlipolysisinadiposetissueandVLDLlevels(降低VLDL),inpartasaresultofdecreasedsecretionbytheliverOnlymodestreductionsofLDLoccurinmostpatients.Inothers,especiallythosewithcombinedhyperlipidemia,LDLoftenincreasesastriglyceridesarereduced.

Hepaticandperipheraleffectsoffibrates贝特类药物作用环节

LPL:lipoproteinlipase;VLDL:very-low-densitylipoprot