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Part4DrugsforTreatmentofCongestiveHeartFailureContentsOverviewACEinhibitorsDiureticsreceptorblockersCardiacglycosideOthersHeart(cardiac)failureissaidtohaveoccurredwhentheheartisnolongerabletomaintainthecirculationtothetissuesfornormalmetabolism.1.Pathophysiologicalchangesofcongestiveheartfailure(CHF)(1)Functionandstructurechanges(2)Increasedsympatheticactivityanddown-regulationofreceptor(3)Activatedrenin-angiotensin-aldosteronesystem(RAAS)A.OverviewPathophysiologicalchangesofCHFPathophysiologicalchangesofCHFCardiacfailureCardiacoutputVenouspressureVenoushyperemiaPulmonarycirculation:cough,emptysis,dyspneaSystemiccirculationhyperemia:jugularveindistension,edemaBloodsupplyRenalbloodflowRenin-angiotensionⅡAldosteroneSodiumandwaterretentionChangesinhemodynamicsofCHFA.Overview2.GradesofCHFⅠ(A):nosymptomsⅡ(B):physicalactivitieswerelimitedandsymptomscouldbeinducedbygeneralactivityⅢ(C):physicalactivitiesweremarkedlylimitedⅣ(D):symptomsappearevenatrest3.TherapeuticstrategiesinCHF(1)Increasingcontractilityofthecardiacmuscles(2)InhibitingRAAS(3)Reducingsympatheticactivity(4)Dilatingvessels(5)DiuresisA.OverviewCardiacremodelingDecreaseoverloadDrugtherapyforCHFACEI:captopril卡托普利enalapril依那普利AT1receptorantagonists:losartan氯沙坦irbesartan伊白沙坦B.Angiotensinconvertingenzymeinhibitors(ACEI)andangiotensinreceptorantagonistsCardiovascularremodelingvasodilatationSystemicandlocalACEI1.PharmacologicaleffectsInhibitingtheproductionofAngIIvasoconstriction;sodiumretention;cardiacremodeling(myocardialhypertrophy)InhibitingthedegradationofbradykininvasodilatationIncreasingANPandscavengingfreeradicalsB.Angiotensinconvertingenzymeinhibitors(ACEI)andangiotensinreceptorantagonistsBoxActionsofangiotensinIIthroughactivatingAT1receptors•Constrictingvessels,increaseperipheralresistanceandreturnedbloodvolume.•Increasingsympathetictension,promotereleaseofsympathetictransmitter.•Stimulatingreleaseofaldosterone.•Rapidlyinducingexpressionofc-fos,c-jun,Egr-1,c-myc,etc.CardiovasculareffectsDecreaseresistanceofperipheralvesselsDilatecoronaryartery,increasebloodsupplyofheartandkidney,improvecardiacandrenalfunctionReversemyocardialhypertrophyandventricularremodelingB.Angiotensinconvertingenzymeinhibitors(ACEI)andangiotensinreceptorantagonistsB.Angiotensinconvertingenzymeinhibitors(ACEI)andangiotensinreceptorantagonists2.Clinicaluses(1)CHFincreasemotortolerancedecreasemortality(2)Hypertension3.AdverseeffectsHypotensionCoughandangioedemaHyperpotassemiaRashesandalteredtastesContraindications:pregnancyandstenosisofrenalarteryB.Angiotensinconvertingenzymeinhibitors(ACEI)andangiotensinreceptorantagonistsAT1receptorantagonistsComparedwithACEI:BlockingactionsofangiotensinIIdirectlyNotaffectingbradykininmetabolismProtectingrenalfunctionUsedforCHFandhypertensionB.Angiotensinconvertingenzymeinhibitors(ACEI)andangiotensinreceptorantagonists1.PharmacologicaleffectsReducebloodvolumebyincreasingNa+andwaterexcretionReduceNa+-Ca2+exchangeinvascularsmoothmusclecells2.ClinicalusesCHF:grandI–IV(mainlyusedinII–III),aloneorcombinedwithotherdrugsEdema,hypertension,etc.3.Adverseeffectsimbalanceofelectrolytes/acid-base;plasmalevelofrenin;hypokalemia;hyperuricemia;hyperglycemia/hyperlipidemiaC.DiureticsTherapeuticeffectsofdiureticsinCHFMaindiureticsThiazidesLoopdiureticsK+sparingdiuretics类别(主要作用部位)其他分类名作用机制利尿应用非利尿应用碳酸酐酶抑制药（近曲小管）/抑制碳酸酐酶利尿药耐受的病人,与袢利尿药合用青光眼，高山病，代谢性碱中毒渗透性利尿药（髓袢及其他部位）脱水药增高尿液渗透压急性肾功能衰竭脑水肿，青光眼袢利尿药（髓袢升支粗段）1.高效能利尿药2.Na+-K+-2C1—同向转运体抑制药抑制Na+-K+-2C1—同向转运各种严重水肿，急性肾功能衰竭高钙血症，加速毒物排出噻嗪类利尿药（远曲小管）1.中效能利尿药2.Na+-C1—同向转运体抑制药抑制Na+-C1—同向转运各种水肿高血压，高尿钙症，尿崩症保钾利尿药（集合管、末段远曲小管）低效能利尿药1.拮抗醛固酮作用（螺内酯）2.抑制上皮细胞Na+通道（氨苯蝶啶，阿米洛利）水肿（尤其对伴有醛固酮增高者，如肝硬化病人）失钾和/或失镁Commonlyused:carvedilol卡维地洛,bisoprolol比索洛尔,sustained-releasemetoprolol缓释型美托洛尔1.Pharmacologicaleffects(1)Blockingeffectsofcatecholaminesonmyocardium:decreasingheartrateandcardiacoxygendemand(2)Up-regulatingreceptor(3)InhibitingRAASandVP(vosopressin,加压素):anti-myocardialhypertrophyandremodeling(4)Reducingcardiacoxygenremand,vasodilatation(receptorblock)(5)Anti-arrhythmicandanti-hypertensiveeffectsD.receptorblockers2.Clinicaluses(1)CHF:grandII-IIIdecreasingmortality(2)Otheruses:hypertension,arrhythmias,angina,etc.D.receptorblockersTherapeuticeffectsofreceptorantagonistsoncardiacfunctioninCHFpatientsD.receptorblockers3.AdverseeffectsInhibitionofcardiacfunctionContraindications:severeheartfailuresevereA-VblockhypotensionworseningbronchialasthmaD.receptorblockersE.Cardiacglycoside(digitalis)Cardiacglycoside:Itisakindofglycosidecompoundswhichcanselectivelyactoncardiacmuscle,andincreasetheforceofmyocardialcontraction.Digoxin地高辛E.Cardiacglycoside(digitalis)1.Pharmacologicaleffects(1)PositiveinotropiceffectsinhibitingNa+-K+-ATPasefreeCa2+excitation-contractioncouplingcardiacoutputorganbloodsupplyVmaxdiastolicdurationvenousreturncoronarybloodsupplycardiacoxygenconsumptionE.Cardiacglycoside(digitalis)InhibitionofNa+-K+-ATPasebydigitalisandpotentiationofcardiacmusclecontraction(2)Negativechronotropicef