第19章治療冠心病藥物

第19章治療冠心病藥物AgentstotreatCHDcoronaryheartdiseaseBackground:IHDistheleadingsinglecauseofdeathintheUSandisresponsiblefor1ofevery4.8deaths.AbouthalfofthepatientswithIHDinitiallypresentwithchronicstableangina.IHDmanifestsasanimbalanceinmyocardialoxygensupplyanddemandthatresultsinmyocardialhypoxemia. IHDisusuallyduetoatheroscleroticdiseaseofthecoronaryarteries(coronaryheartdisease[CHD]andcoronaryarterydisease[CAD])。病因學EtiologyTheexactpathogenesisofCADisnotclear,andnosingletheoryadequatelyexplainstheatheroscleroticprocess.Twomainexplanationshavebeenproposed:thelipidhypothesisandthechronicendothelialinjuryhypothesis.Theseexplanationsareprobablyinterrelatedandarecertainlynotmutuallyexclusive.RiskFactorsPositivefamilyhistory,particularlywithonsetbeforeage50insame-sexparentMalegenderAgeAbnormalitiesinbloodlipids/lipidmetabolism,HighWaist/HipRatio(Rexrodeetal,1998)ElevatedbloodhomocysteineElevatedfibrinogen(Bielaketal,2000)Highultra-sensitiveC-reactiveproteinHighlevelsofironstores(Salonenetal,1992)Lowlevelsofselenium(Suadicanietal,1992)Sedentarylifestyle/poorphysicalfitnessCigarettesmokingAlcoholabuseDietshighinanimalfatandcaloriesandlowinfruits,vegetables,andfiberDietslowinpolyunsaturatedfattyacidsDietshighintransfats(Willettetal,1993)PoorstressmanagementHighbloodlevelsofinsulinDecreasedoxidativeradicalantioxidantcapacity(ORAC)(Fazendasetal,2000)DiabetesmellitusHypertensionHypothyroidismMaritalstress(Orth-Gomer,2002)1．動脈粥樣硬化與冠心病

動脈粥樣硬化是冠心病的病理基礎。

膽固醇等脂質沉著在大中動脈血管壁，形成粥樣斑塊，尤其在動脈分叉處。在心外膜下中等動脈分支的內膜下膽固醇沉著，管腔內新月形隆起，表面為纖維帽，含增殖平滑肌、膠原、脂質及泡沫細胞，內膜下形成壞死區(qū)，含膽固醇結晶、膽固醇酯，鈣鹽等。

冠脈狹窄為偏狹窄，開始為新月形，狹窄<50%為輕度，對供血影響不大，無明顯癥狀；狹窄50%-70%為重度，供血大減，可出現(xiàn)心絞痛。若管腔被血栓迅速阻塞，可產(chǎn)生急性心肌梗死。

冠脈痙攣亦導致缺血性心臟病，可造成心絞痛（如變異型心絞痛），甚至心肌梗死。2．冠心病的臨床分型及表現(xiàn)冠心病共分為五型，分述如下：⑴隱匿型：病人無癥狀，僅心電圖有缺血改變（包括運動試驗），如T波低平，下降，S-T段壓低等。⑵心絞痛（anginapectoris）：心絞痛的發(fā)生是由于心肌耗氧增加或供血不足，導致心肌氧供需失衡所致。⑶急性心肌梗死（acutemyocardialinfarction，AMI）：心肌嚴重缺血缺氧持續(xù)時間過長，導致心肌代謝和功能障礙，心肌細胞壞死。⑷心力衰竭及心律失常型：為長期心肌缺血導致心肌纖維化所致。表現(xiàn)為心臟擴大，心力衰竭及心律失常。⑸猝死型冠心病：因缺血心肌電生理紊亂引起嚴重心律失常所致的原發(fā)性心臟猝死。通常將心絞痛分為穩(wěn)定型心絞痛、不穩(wěn)定型心絞痛和變異型心絞痛三型，現(xiàn)根據(jù)WHO意見將心絞痛分為勞累性和自發(fā)性兩類：①勞累性心絞痛：由體力活動、情緒激動、寒冷或其他增加心肌需氧量的活動誘發(fā)。又分為三種：穩(wěn)定型心絞痛（stableangina）：為最常見的一種類型。病情穩(wěn)定一個月以上，靜息時無癥狀，在勞累或情緒激動時發(fā)病，病情穩(wěn)定，有規(guī)律性。心電圖改變主要有S-T段壓低，T波低平倒置等。初發(fā)勞累性心絞痛：勞累性心絞痛病程在一個月以內。惡化型勞累性心絞痛：同等程度勞累所誘發(fā)的心絞痛發(fā)作次數(shù)、嚴重程度及持續(xù)時間突然加重。②自發(fā)性心絞痛：包括變異型心絞痛（variantangina），較少見。主要由冠脈痙攣所致，在休息靜止時發(fā)作。其特點為發(fā)作與心肌需氧量增加無明顯關系，時間較長，程度較重，且不易為硝酸甘油緩解。心電圖主要表現(xiàn)為S-T段抬高。③不穩(wěn)定型心絞痛：包括初發(fā)勞累性，惡化型，及自發(fā)性心絞痛，易發(fā)生心肌梗死。Pathophysiology

Myocardialischemiareflectsanimbalancebetweenmyocardialoxygensupplyanddemand.Myocardialoxygendemandismainlydeterminedbyheartrate,theforceofventricularcontraction,andventricularwalltension,whichisproportionaltotheventricularvolumeandpressure.Themyocardium'sextractionofoxygenisnearlymaximalintherestingstate.Therefore,intheabsenceofanemiaorsystemichypoxia,anincreaseincoronarybloodflowisessentiallytheonlymechanismavailabletocompensateforincreasesinmyocardialoxygendemand.影響心肌耗氧量的影響心肌收縮力心室壁張力（與心室內壓和心室半徑乘積成正比）心率和射血時間 通常用簡便的方法來估算心肌耗氧量二重乘積（心率×收縮壓，HR×SBP）三重乘積（心率×收縮壓×射血時間(Q-T)，HR×SBP×ET）。 凡使心率加快，血壓升高，心肌收縮加強及心室擴大的因素都可增加心肌氧耗。FactorsthatAffectMyocardialOxygenDemandThemajordeterminantsofmyocardialoxygenconsumptioninclude:ventricularwallstressheartrateinotropicstate(contractility)Bothpreloadandafterloadaffectthestressontheventricularwall"doubleproduct"(HeartRatexSystolicBloodPressure)TreatmentLifestyleMeasures

counselpatientsaboutsmokingcessation,diet,regularexercise,andweightreductionPharmacologicaltreatment PharmacologicaltreatmentofCADcanbedividedintoagentsthatprolongsurvival(eg,aspirin,statindrugs,ACEinhibitors,beta-blockers)andthosethattreatsymptoms(eg,calciumchannelblockers,nitrates).抗血栓形成AspirinhasbeenshowntodecreasemortalityandreinfarctionafteranMI.Administeraspirinimmediately,whichthepatientshouldchewifpossibleuponpresentation.Continueaspirinindefinitelyunlessanobviouscontraindication,suchasableedingtendencyoranallergy,ispresent.ClopidogrelmaybeusedasanalternativetoaspirinincasesofaspirinresistanceorallergyStartallpatientswithsuspectedcoronaryarterydisease(CAD)orischemicheartdisease(IHD)onaspirin(75to150milligrams[mg]onetimeaday),unlesscontraindicatedAspirinreducestheriskofadversecardiovasculareventsby25%to33%inpatientswithstableangina.Clopidogrel(75mgaday)appearstobeaseffectiveasaspirin,butitismuchmoreexpensive;itisrecommendedforpatientswithcontraindication(s)toaspirin緩解心絞痛

Threecategoriesofagentsareusedinthetreatmentofangina1.

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

Calciumchannelblockers(reduceafterload,vasodilatecoro