充血性心衰藥物演示文稿

充血性心衰藥物演示文稿當前第1頁\共有33頁\編于星期二\23點優(yōu)選充血性心衰藥物Ppt當前第2頁\共有33頁\編于星期二\23點Concept: CHFisacomplexclinicalsyndromecharacterizedbyimpairedventricularperformance,exerciseintolerance,ahighincidenceofventriculararrhythmias,andshortenedlifeexpectancy當前第3頁\共有33頁\編于星期二\23點Thesignsandsymptoms

Thesignsandsymptomsofheartfailureincludetachycardia,decreasedexercisetoleranceandshortnessofbreath,peripheralandpulmonaryedema,andcardiomegaly.

動脈系統(tǒng)缺血-乏力，氣短，頭暈 靜脈系統(tǒng)淤血-水腫，頸靜脈怒張，肝脾腫大，呼吸困難靜脈淤血所致的癥狀為主。當前第4頁\共有33頁\編于星期二\23點心衰的分級（NYHA標準）Ⅰ級：心功能代償完全，體力活動不受限，日?；顒訜o乏力，心悸，呼吸困難等癥狀；Ⅱ級：輕度代償不全，活動輕度受限，休息時無癥狀；Ⅲ級：中度代償不全，體力活動明顯受限，日?；顒蛹纯僧a(chǎn)生癥狀。限于室內(nèi)活動；Ⅳ級：嚴重代償不全，休息時亦有癥狀，不能從事任何體力活動。當前第5頁\共有33頁\編于星期二\23點 心力衰竭不是一種獨立的疾病，而是由多種原因引起的心肌收縮和/或舒張功能障礙的綜合征。近年來的研究發(fā)現(xiàn)，心力衰竭雖然主要表現(xiàn)為心肌收縮和舒張功能障礙，但神經(jīng)內(nèi)分泌的改變對其惡性循環(huán)的形成和維持有重要的作用。這些變化導致心臟出現(xiàn)不可逆的重構(gòu)(remodeling)，使衰竭的心臟一步步惡化。Pathophysiology當前第6頁\共有33頁\編于星期二\23點心力衰竭時機體的代償機制:AugmentedsympatheticactivitySodiumandwaterretentionMyocardialhypertrophyVentriculardilatation1．心臟本身的代償 心率加快、心肌收縮加強--快速發(fā)生 心臟擴大和肥大—緩慢發(fā)生 是心臟本身儲備功能的動員。2．心臟外的代償 血容量增加 血液重分配及紅細胞增多 等幾方面的心臟外代償作用。當前第7頁\共有33頁\編于星期二\23點 機體的代償機制雖然有助于維持機體所需的心輸出量要求，但長時間代償機制的激活可加重心臟的負擔。 在CHF的長期發(fā)病過程中，各種代償機制對心臟和動脈血管等的影響可產(chǎn)生惡性循環(huán)，加重心臟負擔，最終加重心力衰竭。實際上慢性心衰的發(fā)展過程就是在心肌氧供不足和維持機體循環(huán)血供需求之間不斷平衡的矛盾發(fā)展過程。當前第8頁\共有33頁\編于星期二\23點神經(jīng)體液系統(tǒng)主要改變Increasedsympatheticnervoussystemactivity(andincreasedplasmacatecholamines,b-receptordownregulation)Increasedactivityoftherenin-angiotensin-aldosteronesystem

Increasedreleaseofarginine-vasopressin

當前第9頁\共有33頁\編于星期二\23點心衰的一些代償機制Inadditiontotheeffectsshown,angiotensinIIincreasessympatheticeffectsbyfacilitatingnorepinephrinerelease.

當前第10頁\共有33頁\編于星期二\23點慢性心衰的藥物治療：

應減輕負荷，降低能耗，保護心臟。達到改善血流動力學；改善運動耐量；延長生命。

而不是病馬加鞭，只增強心肌收縮力心衰的血流動力學指標：壓力指標：LVEDP，±dP/dtmax；容積指標：SV，CO，CI，EF（正常0.67,心衰<0.45,嚴重心衰<0.3）時間指標：PEP，LVET，T-dP/dtmax當前第11頁\共有33頁\編于星期二\23點抗心衰藥物的發(fā)展和演變洋地黃時代（從民間的治療水腫藥物而來）利尿藥（噻嗪類、汞撒利）非苷類強心藥（兒茶酚胺類，磷酸二酯酶抑制劑-氨力農(nóng)、米力農(nóng)）擴血管藥物血管緊張素轉(zhuǎn)化酶抑制劑ACEIs，ARBsβ受體阻斷劑醛固酮受體阻斷劑當前第12頁\共有33頁\編于星期二\23點使用抗心衰藥物后心功能曲線的改變(I)正性肌力藥物positiveinotropicagents(V)舒血管藥Vasodilators(D)利尿藥Diuretics當前第13頁\共有33頁\編于星期二\23點pharmacologicintervention

inCHF 抗心衰藥物是主要用于治療CHF的藥物，主要有強心苷、非甙類正性肌力藥、利尿藥、ACEI和β受體阻斷藥等。Improvinghemodynamicswithinotropicdrugsdoesnotdecreasemortality;（病馬加鞭）long-termtreatmentdirectedtowardsneurohormonalfactorswithACEinhibitorsandbeta-blockerscandecreasemortality當前第14頁\共有33頁\編于星期二\23點ConsensusrecommendationsforthemanagementofCHFPatientswithheartfailureshouldfirstbeevaluatedtoassessLVejectionfraction.Patientswithsystolicdysfunction(EF<40%)shouldthenundergothefollowingtreatment:水鈉潴留：利尿藥ACEIs，ARBs和/或beta-blocker室率快的房顫：強心苷（地高辛）重癥患者延長壽命：醛固酮受體拮抗劑當前第15頁\共有33頁\編于星期二\23點fluidretention-adiuretic.ACEinhibitorandbeta-blockershouldbeinitiatedandmaintainedunlessspecificallycontraindicated.（Patientswithsevereheartfailureshouldprobablynotreceiveabeta-blocker）Digoxin-inpatientswithrapidatrialfibrillation.Spironolactone,analdosteroneantagonist,mayreducemortalityinpatientswithsevereheartfailure當前第16頁\共有33頁\編于星期二\23點ACEinhibitorsfirst-linetherapyinallpatientswithheartfailure

improvesymptoms,slowprogressionofthedisease,reducemortality,anddecreasetheincidenceofhospitalizationThemostcommonadverseeffectsofACEinhibitorsaredirectlyrelatedtoloweringangiotensinIIconcentrations(hypotensionandrenalinsufficiency)andincreasingconcentrationsofkinins(coughandangioneuroticedema)當前第17頁\共有33頁\編于星期二\23點血管緊張素原AngiotensinⅠ收縮血管腎素激肽原緩激肽↑降解失活AngⅢACEACEIsAngⅡ

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分泌醛固酮NOPGI(-)ACE和ACEIs作用示意圖舒張血管當前第18頁\共有33頁\編于星期二\23點Captopril第1個在臨床上廣泛應用的ACEI。含巰基，可致味覺異常。Enalapril前體藥，不含巰基。藥效和作用時間比cartopril強。當前第19頁\共有33頁\編于星期二\23點ARBs-angiotensinreceptorblockersangiotensinreceptorantagonists(AT1ReceptorAntagonists)areaseffectiveasACEinhibitorsintreatingheartfailure,butitappearsthattherapeuticefficacymaybecomparablelosartan,candesartan,valsartan當前第20頁\共有33頁\編于星期二\23點InotropicDrugs-digitalisThebeneficialeffectsofcardiacglycosidesinthetreatmentofheartfailurehavebeenattributedtoapositiveinotropiceffectonfailingmyocardiumandefficacyincontrollingtheventricularrateresponsetoatrialfibrillation.Thecardiacglycosidesalsomodulateautonomicnervoussystemactivity,anditislikelythatthismechanismcontributessubstantiallytotheirefficacyinthemanagementofheartfailure.當前第21頁\共有33頁\編于星期二\23點PositiveInotropicEffect

（抑制Na+,K+-ATPase）ElectrophysiologicalActions

（加上增強迷走）RegulationofSympatheticNervousSystemActivity

Thereisevidencethatdigitalismayactdirectlytosensitizationofbaroreceptorresponseandtherebyexertsomeofitsbeneficialeffectsthroughreductionofsympathetictone

當前第22頁\共有33頁\編于星期二\23點TherecentDigitalisInvestigationGroup(DIG)clinicaltrialindicateddigoxindidnotreduceoverallmortalityinpatientswithheartfailure(whowerereceivingdiureticsandACEinhibitors),butdidreducetherateofhospitalization當前第23頁\共有33頁\編于星期二\23點Otherinotropicagents 只適用于急性心衰，長期應用于慢性心衰后，病人死亡率增加。Beta-AdrenergicAgonistsdopamine,dobutamine,prenalterolLevodopaandibopamineCyclicNucleotidePhosphodiesterase(PDE-III,cGMP-inhibitablePDE)InhibitorsBipyridines-amrinoneandmilrinone

imidazolonederivatives-enoximoneandpiroximone

當前第24頁\共有33頁\編于星期二\23點Beta-BlockersandCHFAnumberofstudiesbeginninginthe1970shaveshownthatbeta-blockerscanimprovesymptomsandventricularfunctioninpatientswithmoderatetosevereheartfailure,andmayslowtheprogressionofheartfailureinsomepatients(reviewedinBristow,Circulation101:558(2000))

當前第25頁\共有33頁\編于星期二\23點Thoughbeta-blockerswerewidelyconsideredtobecontraindicatedforpatientswithheartfailureonlyadecadeago,theyarenowconsideredfirst-linetherapyforpatientswithmildtomoderateheartfailure現(xiàn)認為脂溶性的效果更好。metoprololcarvedilolbisoprolol當前第26頁\共有33頁\編于星期二\23點Theadverseeffects:worseningofsymptoms,hypotension,andbradycardiaThesesymptomscanbeminimizedbyinitiatingtherapywithlowdosesandgraduallyincreasingdosageuntiltolerabletherapeuticdosesarereachedBeta-blockersarecontraindicatedinpatientswithasthmaorseverebradycardia當前第27頁\共有33頁\編于星期二\23點DiureticsMostpateintswithheartfailurerequiretreatmentwithdiureticstorelievesymptomsoffluidretention(edemaandcongestion),buttheirisnoevidencethatdiureticsslowtheprogressionofthediseaseordecreasemortality.Loopdiuretics(furosemide)arethemosteffectivediuretics多用于嚴重水鈉潴留和腎功能不全時。Thiazidediureticsactonthedistalloopandarelesseffectivethanloopdiuretics用于輕度水鈉潴留。Concurrentuseoftwodiureticswithdifferentsitesofactionmaybeneededinpatientswhodonotrespondwelltoasingleoraldiuretic當前第28頁\共有33頁\編于星期二\23點Themostcommonadverseeffectofdiuretictherapyispotassiumdepletionwhichcanbepreventedbyuseofsupplementalpotassium,anACEinhibitor,orapotassium-sparingdiuretic(spironolactoneoramiloride)AldosteroneAntagonists Recentclinicaltrialsindicatethataddingspironolactone(螺內(nèi)酯)tostandardtreatmentcansignificantlydecreasemortalityinpatientswithsevereheartfailure當前第29頁\共有33頁\編于星期二\23點Effectofspironolactoneonsurvivalinpatientswithmoderateorseverecongestiveheartfailureinarandomizeddouble-blindclinicalstudy.(Reproduced,withpermission,fromPittBetal:Theeffectofspironolactoneonmorbidityandmortalityinpatientswithsevereheartfailure.NEnglJMed1999;341:709醛固酮受體拮抗劑螺內(nèi)酯降低充血性心衰病人死亡率當前第30頁\共有33頁\編于星期二\23點OtherAgentswithTherapaeuticPotential

Endothelin-1Antagonists

Thevasoconstrictorpeptide,endothelin-1,isknowntobeelevatedinheartfailureandisapredictorofmortalityinpatientswithheartfailure.Animalmodelsofheartfailureindicateendothelinreceptorantagonistssuchasbosentanmayhavelong-termbenefitsinreversingmyocardialremodelingandimprovingsurvival.Short-term,small-scaletrialsinhumansindicatepossiblebeneficialeffectsonsystemicandpulmonaryhemodynamics當前第31頁\共有33頁\編于星期二\23點xanthineoxidaseinhibitorBackground:Highserumuricacid(SUA)levelsareastrong,independentmarkerofimpairedprognosisinpatientswithmoderatetosevereCHF.Resultsand