治疗冠心病药物

治疗冠心病药物第1页/共25页coronaryheartdiseaseBackground:IHDistheleadingsinglecauseofdeathintheUSandisresponsiblefor1ofevery4.8deaths.AbouthalfofthepatientswithIHDinitiallypresentwithchronicstableangina.IHDmanifestsasanimbalanceinmyocardialoxygensupplyanddemandthatresultsinmyocardialhypoxemia. IHDisusuallyduetoatheroscleroticdiseaseofthecoronaryarteries(coronaryheartdisease[CHD]andcoronaryarterydisease[CAD])。第2页/共25页病因学EtiologyTheexactpathogenesisofCADisnotclear,andnosingletheoryadequatelyexplainstheatheroscleroticprocess.Twomainexplanationshavebeenproposed:thelipidhypothesisandthechronicendothelialinjuryhypothesis.Theseexplanationsareprobablyinterrelatedandarecertainlynotmutuallyexclusive.第3页/共25页RiskFactorsPositivefamilyhistory,particularlywithonsetbeforeage50insame-sexparentMalegenderAgeAbnormalitiesinbloodlipids/lipidmetabolism,HighWaist/HipRatio(Rexrodeetal,1998)ElevatedbloodhomocysteineElevatedfibrinogen(Bielaketal,2000)Highultra-sensitiveC-reactiveproteinHighlevelsofironstores(Salonenetal,1992)Lowlevelsofselenium(Suadicanietal,1992)Sedentarylifestyle/poorphysicalfitness第4页/共25页CigarettesmokingAlcoholabuseDietshighinanimalfatandcaloriesandlowinfruits,vegetables,andfiberDietslowinpolyunsaturatedfattyacidsDietshighintransfats(Willettetal,1993)PoorstressmanagementHighbloodlevelsofinsulinDecreasedoxidativeradicalantioxidantcapacity(ORAC)(Fazendasetal,2000)DiabetesmellitusHypertensionHypothyroidismMaritalstress(Orth-Gomer,2002)第5页/共25页1．动脉粥样硬化与冠心病

动脉粥样硬化是冠心病的病理基础。胆固醇等脂质沉着在大中动脉血管壁，形成粥样斑块，尤其在动脉分叉处。在心外膜下中等动脉分支的内膜下胆固醇沉着，管腔内新月形隆起，表面为纤维帽，含增殖平滑肌、胶原、脂质及泡沫细胞，内膜下形成坏死区，含胆固醇结晶、胆固醇酯，钙盐等。

冠脉狭窄为偏狭窄，开始为新月形，狭窄<50%为轻度，对供血影响不大，无明显症状；狭窄50%-70%为重度，供血大减，可出现心绞痛。若管腔被血栓迅速阻塞，可产生急性心肌梗死。

冠脉痉挛亦导致缺血性心脏病，可造成心绞痛（如变异型心绞痛），甚至心肌梗死。第6页/共25页2．冠心病的临床分型及表现冠心病共分为五型，分述如下：⑴隐匿型：病人无症状，仅心电图有缺血改变（包括运动试验），如T波低平，下降，S-T段压低等。⑵心绞痛（anginapectoris）：心绞痛的发生是由于心肌耗氧增加或供血不足，导致心肌氧供需失衡所致。⑶急性心肌梗死（acutemyocardialinfarction，AMI）：心肌严重缺血缺氧持续时间过长，导致心肌代谢和功能障碍，心肌细胞坏死。⑷心力衰竭及心律失常型：为长期心肌缺血导致心肌纤维化所致。表现为心脏扩大，心力衰竭及心律失常。⑸猝死型冠心病：因缺血心肌电生理紊乱引起严重心律失常所致的原发性心脏猝死。第7页/共25页通常将心绞痛分为稳定型心绞痛、不稳定型心绞痛和变异型心绞痛三型，现根据WHO意见将心绞痛分为劳累性和自发性两类：①劳累性心绞痛：由体力活动、情绪激动、寒冷或其他增加心肌需氧量的活动诱发。又分为三种：稳定型心绞痛（stableangina）：为最常见的一种类型。病情稳定一个月以上，静息时无症状，在劳累或情绪激动时发病，病情稳定，有规律性。心电图改变主要有S-T段压低，T波低平倒置等。初发劳累性心绞痛：劳累性心绞痛病程在一个月以内。恶化型劳累性心绞痛：同等程度劳累所诱发的心绞痛发作次数、严重程度及持续时间突然加重。②自发性心绞痛：包括变异型心绞痛（variantangina），较少见。主要由冠脉痉挛所致，在休息静止时发作。其特点为发作与心肌需氧量增加无明显关系，时间较长，程度较重，且不易为硝酸甘油缓解。心电图主要表现为S-T段抬高。③不稳定型心绞痛：包括初发劳累性，恶化型，及自发性心绞痛，易发生心肌梗死。第8页/共25页Pathophysiology

Myocardialischemiareflectsanimbalancebetweenmyocardialoxygensupplyanddemand.Myocardialoxygendemandismainlydeterminedbyheartrate,theforceofventricularcontraction,andventricularwalltension,whichisproportionaltotheventricularvolumeandpressure.Themyocardium'sextractionofoxygenisnearlymaximalintherestingstate.Therefore,intheabsenceofanemiaorsystemichypoxia,anincreaseincoronarybloodflowisessentiallytheonlymechanismavailabletocompensateforincreasesinmyocardialoxygendemand.第9页/共25页影响心肌耗氧量的影响心肌收缩力心室壁张力（与心室内压和心室半径乘积成正比）心率和射血时间 通常用简便的方法来估算心肌耗氧量二重乘积（心率×收缩压，HR×SBP）三重乘积（心率×收缩压×射血时间(Q-T)

，HR×SBP×ET）。 凡使心率加快，血压升高，心肌收缩加强及心室扩大的因素都可增加心肌氧耗。第10页/共25页FactorsthatAffectMyocardialOxygenDemandThemajordeterminantsofmyocardialoxygenconsumptioninclude:ventricularwallstressheartrateinotropicstate(contractility)Bothpreloadandafterloadaffectthestressontheventricularwall"doubleproduct"(HeartRatexSystolicBloodPressure)第11页/共25页TreatmentLifestyleMeasures

counselpatientsaboutsmokingcessation,diet,regularexercise,andweightreductionPharmacologicaltreatment PharmacologicaltreatmentofCADcanbedividedintoagentsthatprolongsurvival(eg,aspirin,statindrugs,ACEinhibitors,beta-blockers)andthosethattreatsymptoms(eg,calciumchannelblockers,nitrates).第12页/共25页抗血栓形成AspirinhasbeenshowntodecreasemortalityandreinfarctionafteranMI.Administeraspirinimmediately,whichthepatientshouldchewifpossibleuponpresentation.Continueaspirinindefinitelyunlessanobviouscontraindication,suchasableedingtendencyoranallergy,ispresent.Clopidogrelmaybeusedasanalternativetoaspirinincasesofaspirinresistanceorallergy第13页/共25页Startallpatientswithsuspectedcoronaryarterydisease(CAD)orischemicheartdisease(IHD)onaspirin(75to150milligrams[mg]onetimeaday),unlesscontraindicatedAspirinreducestheriskofadversecardiovasculareventsby25%to33%inpatientswithstableangina.Clopidogrel(75mgaday)appearstobeaseffectiveasaspirin,butitismuchmoreexpensive;itisrecommendedforpatientswithcontraindication(s)toaspirin第14页/共25页缓解心绞痛

Threecategoriesofagentsareusedinthetreatmentofangina1.

Organicnitrates(reducepreload,reduceafterload,vasodilatecoronaryarteries,inhibitplateletaggregation)2.

Calciumchannelblockers(reduceafterload,vasodilatecoronaryarteries,mayinhibitplateletaggregation;somealsodecreaseheartrate,decreasecontractility)第15页/共25页3.

Beta-adrenergicantagonists(decreaseheartrate,decreasecontractility,decreaseafterloadduetodecreaseincardiacoutput,mayinhibitplateletaggregation)第16页/共25页硝酸酯及亚硝酸酯是缓解心绞痛的主要药物增加氧供，改善侧支循环降低心室内压，改善心内膜下心肌供血（此处常是缺血最严重的部位），舒张冠脉痉挛减少氧耗舒张外周静脉和动脉血管，降低心脏前后负荷，缩小心室容积一般短效，可产生反射性心动过速第17页/共25页Beta-阻断剂阻断交感对心脏的兴奋作用，减慢心率，抑制心肌收缩，降低氧耗量对劳作型心绞痛效好，对变异性无效？可用于先兆心肌梗死和急性心肌梗死第18页/共25页钙拮抗剂舒张动静脉血管，减轻后负荷和前负荷冠脉解痉效果好，最适用于变异性心绞痛要用长效药物，短效者可使血压波动过大，兴奋交感第19页/共25页Usebeta-blockersasfirst-lineanti-anginaltherapy,unlesscontraindicated.Beta-blockersdecreasemyocardialoxygendemandbydecreasingmyocardialcontractility,arterial(blood)pressure,andheartrate.Leftventricularperfusionisenhancedbytheincreaseddurationofdiastole.Ofallofthemedicationsusedintreatinganginapectoris,onlybeta-blockershaveconclusivelybeenshowntoreducebothclinicalsymptomsandcardiacevents.However,emergingdatasuggestthatangiotensin-convertingenzyme(ACE)inhibitorsandstatinsalsoreduceclinicalsymptomsandcardiacevents.第20页/共25页combinationtherapyBeta-blockersandnitratesarefrequentlyusedtogetherinpatientswithchronicstableangina,becausetheircombineduseappearstobemoreeffectivethanmonotherapywitheitheragent.Theconcurrentuseofbeta-blockersattenuatesthetendencyofnitratestoincreasesympathetictoneandcausereflextachycardia.Thepotentialincreaseinleftventricularvolume,end-diastolicpressure,andwalltension,andthepotentialdecreaseinheartratewithbeta-blockers,arecounteractedbytheconcurrentuseofnitroglycerin.第21页/共25页对心肌梗死的治疗冠脉血栓心肌梗死。梗塞范围大可致心源性休克，心律失常，心衰，心脏破裂，死亡率高