第17章治疗充血性心力衰竭药物

第17章治疗充血性心力衰竭药物

DrugsforCongestiveHeartFailure 慢性或充血性心力衰竭（congestiveheartfailure,CHF）是各种病因所引起的多种心脏疾病（冠心、高心、肺心、风心、心肌病等）的终末阶段，当静脉回流足够的情况下，心脏排出量绝对或相对减少，不能满足机体组织需求的一种临床或病理综合征。心衰病人运动耐量下降，寿命缩短。Concept: CHFisacomplexclinicalsyndromecharacterizedbyimpairedventricularperformance,exerciseintolerance,ahighincidenceofventriculararrhythmias,andshortenedlifeexpectancyThesignsandsymptoms

Thesignsandsymptomsofheartfailureincludetachycardia,decreasedexercisetoleranceandshortnessofbreath,peripheralandpulmonaryedema,andcardiomegaly.

动脉系统缺血-乏力，气短，头晕 静脉系统淤血-水肿，颈静脉怒张，肝脾肿大，呼吸困难静脉淤血所致的症状为主。 心力衰竭不是一种独立的疾病，而是由多种原因引起的心肌收缩和/或舒张功能障碍的综合征。近年来的研究发现，心力衰竭虽然主要表现为心肌收缩和舒张功能障碍，但神经内分泌的改变对其恶性循环的形成和维持有重要的作用。Pathophysiology心力衰竭时机体的代偿机制:AugmentedsympatheticactivitySodiumandwaterretentionMyocardialhypertrophyVentriculardilatation1．心脏本身的代偿 心率加快、心肌收缩加强--快速发生 心脏扩大和肥大—缓慢发生 是心脏本身储备功能的动员。2．心脏外的代偿 血容量增加 血液重分配及红细胞增多 等几方面的心脏外代偿作用。 机体的代偿机制虽然有助于维持机体所需的心输出量要求，但长时间代偿机制的激活可加重心脏的负担。 在CHF的长期发病过程中，各种代偿机制对心脏和动脉血管等的影响可产生恶性循环，加重心脏负担，最终加重心力衰竭。神经体液系统主要改变Increasedsympatheticnervoussystemactivity(andincreasedplasmacatecholamines,b-receptordownregulation)Increasedactivityoftherenin-angiotensin-aldosterone

system

Increasedreleaseofarginine-vasopressin

心衰的一些代偿机制Inadditiontotheeffectsshown,angiotensinIIincreasessympatheticeffectsbyfacilitatingnorepinephrinerelease.

心衰的分级（NYHA标准）Ⅰ级：心功能代偿完全，体力活动不受限，日常活动无乏力，心悸，呼吸困难等症状；Ⅱ级：轻度代偿不全，活动轻度受限，休息时无症状；Ⅲ级：中度代偿不全，体力活动明显受限，日常活动即可产生症状。限于室内活动；Ⅳ级：严重代偿不全，休息时亦有症状，不能从事任何体力活动。慢性心衰的药物治疗：

应减轻负荷，降低能耗，保护心脏。达到改善血流动力学；改善运动耐量；延长生命。

而不是病马加鞭，只增强心肌收缩力心衰的血流动力学指标：压力指标：LVEDP，±dP/dtmax；容积指标：SV，CO，CI，EF（正常0.67,心衰

<0.45,严重心衰<0.3）时间指标：PEP，LVET，T-dP/dtmax使用抗心衰药物后心功能曲线的改变(I)正性肌力药物positiveinotropicagents(V)舒血管药Vasodilators(D)利尿药Diureticspharmacologicintervention

inCHF 抗心衰药物是主要用于治疗CHF的药物，主要有强心苷、非甙类正性肌力药、利尿药、ACEI和β受体阻断药等。Improvinghemodynamicswithinotropicdrugsdoesnotdecreasemortality;（病马加鞭）long-termtreatmentdirectedtowardsneurohormonalfactorswithACEinhibitorsandbeta-blockerscandecreasemortalityConsensusrecommendationsforthemanagementofCHFPatientswithheartfailureshouldfirstbeevaluatedtoassessLVejectionfraction.Patientswithsystolicdysfunction(EF<40%)shouldthenundergothefollowingtreatment:水钠潴留：利尿药ACEIs

和/或beta-blocker室率快的房颤：强心苷（地高辛）重症患者延长寿命：醛固酮受体拮抗剂fluidretention-adiuretic.ACEinhibitorandbeta-blockershouldbeinitiatedandmaintainedunlessspecificallycontraindicated.（Patientswithsevereheartfailureshouldprobablynotreceiveabeta-blocker）Digoxin

-inpatientswithrapidatrialfibrillation.Spironolactone,analdosteroneantagonist,mayreducemortalityinpatientswithsevereheartfailureInotropicDrugs-digitalisThebeneficialeffectsofcardiacglycosidesinthetreatmentofheartfailurehavebeenattributedtoapositiveinotropiceffectonfailingmyocardiumandefficacyincontrollingtheventricularrateresponsetoatrialfibrillation.Thecardiacglycosidesalsomodulateautonomicnervoussystemactivity,anditislikelythatthismechanismcontributessubstantiallytotheirefficacyinthemanagementofheartfailure.PositiveInotropicEffect

（抑制Na+,K+-ATPase

）ElectrophysiologicalActions

（加上增强迷走）RegulationofSympatheticNervousSystemActivity

Thereisevidencethatdigitalismayactdirectlytosensitizationof

baroreceptorresponseandtherebyexertsomeofitsbeneficialeffectsthroughreductionofsympathetictone

TherecentDigitalisInvestigationGroup(DIG)clinicaltrialindicateddigoxindidnotreduceoverallmortalityinpatientswithheartfailure(whowerereceivingdiureticsandACEinhibitors),butdidreducetherateofhospitalizationOtherinotropicagents 只适用于急性心衰，长期应用于慢性心衰后，病人死亡率增加。Beta-AdrenergicAgonistsdopamine,dobutamine,prenalterol

Levodopaandibopamine

CyclicNucleotidePhosphodiesterase(PDE-III,cGMP-inhibitablePDE)InhibitorsBipyridines-amrinoneandmilrinone

imidazolonederivatives-enoximoneandpiroximone

ACEinhibitorsfirst-linetherapyinallpatientswithheartfailure

improvesymptoms,slowprogressionofthedisease,reducemortality,anddecreasetheincidenceofhospitalizationThemostcommonadverseeffectsofACEinhibitorsaredirectlyrelatedtoloweringangiotensinIIconcentrations(hypotensionandrenalinsufficiency)andincreasingconcentrationsofkinins(coughandangioneuroticedema)ARBs-angiotensinreceptorblockersangiotensinreceptorantagonists(AT1ReceptorAntagonists)losartan,candesartan,valsartanareaseffectiveasACEinhibitorsintreatingheartfailure,butitappearsthattherapeuticefficacymaybecomparableBeta-BlockersandCHFAnumberofstudiesbeginninginthe1970shaveshownthatbeta-blockerscanimprovesymptomsandventricularfunctioninpatientswithmoderatetosevereheartfailure,andmayslowtheprogressionofheartfailureinsomepatients(reviewedinBristow,Circulation101:558(2000))

Thoughbeta-blockerswerewidelyconsideredtobecontraindicatedforpatientswithheartfailureonlyadecadeago,theyarenowconsideredfirst-linetherapyforpatientswithmildtomoderateheartfailureTheadverseeffects:worseningofsymptoms,hypotension,andbradycardia

ThesesymptomscanbeminimizedbyinitiatingtherapywithlowdosesandgraduallyincreasingdosageuntiltolerabletherapeuticdosesarereachedBeta-blockersarecontraindicatedinpatientswithasthmaorseverebradycardiaDiureticsMostpateintswithheartfailurerequiretreatmentwithdiureticstorelievesymptomsoffluidretention(edemaandcongestion),buttheirisnoevidencethatdiureticsslowtheprogressionofthediseaseordecreasemortality.Loopdiuretics(furosemide)arethemosteffectivediureticsThiazidediureticsactonthedistalloopandarelesseffectivethanloopdiureticsConcurrentuseoftwodiureticswithdifferentsitesofactionmaybeneededinpatientswhodonotrespondwelltoasingleoraldiureticThemostcommonadverseeffectofdiuretictherapyispotassiumdepletionwhichcanbepreventedbyuseofsupplementalpotassium,anACEinhibitor,orapotassium-sparingdiuretic(spironolactoneoramiloride)AldosteroneAntagonists Recentclinicaltrialsindicatethataddingspironolactone(螺内酯)tostandardtreatmentcansignificantlydecreasemortalityinpatientswithsevereheartfailureOtherAgentswithTherapaeuticPotential

Endothelin-1AntagonistsThevasoconstrictorpeptide,endothelin-1,isknowntobeelevatedinheartfailureandisapredictorofmortalityinpatientswithheartfailure.Animalmodelsofheartfailureindicateendothelinreceptorantagonistssuchasbosentanmayhavelong-termbenefitsinreversingmyocardialremodelingandimprovingsurvival.Short-term,small-scaletrialsinhumansindicatepossiblebeneficialeffectsonsystemicandpulmonaryhemodynamics

Stepsinthetreatmentofchronicheartfailure.________________________________________ 1.Reduceworkloadoftheheart

a.Limitactivitylevel

b.Reduceweight

c.Controlhypertension

2.Restrictsodium

3.Restrictwater(rarelyrequired)

4.Givediuretics

5.GiveACEinhibitoranddigitalis1

6.Giveb-blockerstopatientswithstableclassII-IIIheartfailure

7.Givevas