充血性心衰药物

治疗充血性心力衰竭药物

DrugsforCongestiveHeartFailure

心力衰竭（heartfailure）是各种原因引起的心肌舒缩障碍，导致心输出量不能满足机体需求的一组临床综合征。充血性心衰是其中最主要的一种。 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。 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。这些变化导致心脏出现不可逆的重构(remodeling)，使衰竭的心脏一步步恶化。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。实际上慢性心衰的发展过程就是在心肌氧供不足和维持机体循环血供需求之间不断平衡的矛盾发展过程。神经体液系统主要改变Increasedsympatheticnervoussystemactivity(andincreasedplasmacatecholamines,b-receptordownregulation)Increasedactivityoftherenin-angiotensin-aldosteronesystem

Increasedreleaseofarginine-vasopressin

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

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抗心衰药物的发展和演变洋地黄时代（从民间的治疗水肿药物而来）利尿药（噻嗪类、汞撒利）非苷类强心药（儿茶酚胺类，磷酸二酯酶抑制剂-氨力农、米力农）扩血管药物血管紧张素转化酶抑制剂ACEIs，ARBsβ受体阻断剂醛固酮受体阻断剂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，ARBs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,mayreducemortalityinpatientswithsevereheartfailureACEinhibitorsfirst-linetherapyinallpatientswithheartfailure

improvesymptoms,slowprogressionofthedisease,reducemortality,anddecreasetheincidenceofhospitalizationThemostcommonadverseeffectsofACEinhibitorsaredirectlyrelatedtoloweringangiotensinIIconcentrations(hypotensionandrenalinsufficiency)andincreasingconcentrationsofkinins(coughandangioneuroticedema)血管紧张素原AngiotensinⅠ收缩血管肾素激肽原缓激肽↑降解失活AngⅢACEACEIsAngⅡ

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分泌醛固酮NOPGI(-)ACE和ACEIs作用示意图舒张血管Captopril第1个在临床上广泛应用的ACEI。含巯基，可致味觉异常。Enalapril前体药，不含巯基。药效和作用时间比cartopril强。ARBs-angiotensinreceptorblockersangiotensinreceptorantagonists(AT1ReceptorAntagonists)areaseffectiveasACEinhibitorsintreatingheartfailure,butitappearsthattherapeuticefficacymaybecomparablelosartan,candesartan,valsartanInotropicDrugs-digitalisThebeneficialeffectsofcardiacglycosidesinthetreatmentofheartfailurehavebeenattributedtoapositiveinotropiceffectonfailingmyocardiumandefficacyincontrollingtheventricularrateresponsetoatrialfibrillation.Thecardiacglycosidesalsomodulateautonomicnervoussystemactivity,anditislikelythatthismechanismcontributessubstantiallytotheirefficacyinthemanagementofheartfailure.Pos戴iti召ve捕Ino掉tro亿pic服Ef级fec亩t（抑制Na+,含K+-A恋TPas沉e）Elec味trop读hysi偏olog忠ical名Act台ions（加上闹增强迷歼走）Reg贴ula饺tio浴no趣fS翼ymp挠ath烘eti驴cN扭erv弃ous垄Sy染ste嫁mA瓜cti馒vit垮yTher考eis午evi门denc栽eth持atd障igit堤alis剪may贡act混dir赚ectl辟ytosen略sit黑iza壮tio拘no善fbaro咱rece里ptor纪res吓pons恢ean抽dth关ereb忧yex永ert绍some衣of板its推bene惕fici吼ale氧ffec痰tst要hrou崖ghr金educ辛tion拾of请symp里athe虚tic哄toneThe携rece斑ntD质igit搅alis烈Inv针esti帽gati有onG食roup蛇(DI唱G)c盯lini游cal舱tria寸lin忧dica测ted艰digo倚xin蔑did插not笛redu伪ceo茧vera拢llm统orta腔lity乳in导pati圆ents掩wit叔hhe粒art特fail虚ure亲(who挺wer芒ere乓ceiv耍ing僵diur粥etic区san盗dAC毫Ein溜hibi纸tors膀),b解utd蝴idr叛educ有eth痕era策teo住fho丢spit园aliz腐atio烤nOth蛙er隆ino间tro氧pic愚ag施ent勒s只适用于君急性心衰兽，长期应形用于慢性涉心衰后，痛病人死亡胖率增加。Bet另a-A灶dre雷ner深gic皮Ag春oni漆stsdop竟ami醒ne,收do幸but丈ami搅ne,热pr粮ena蚂lte殿rolLevo糕dopa汪and较ibo永pami捞neCycl鲁icN刻ucle临otid信ePh帜osph溉odie特ster蒙ase拒(PDE尊-III放,cG鸭MP-i泼nhib瓦itab互leP典DE)缩慧Inhi页bito宇rsBipy敌ridi怠nes-视amr缸inon梳ean幸dmi怠lrin咱oneimi松daz悬olo遗ne砍der佣iva践tiv六es-于en充oxi半mon消ea疲nd竖pir型oxi枯mon寒eBet呢a-B涛loc犯ker从sa便nd脂CHFAn效umb烂er与of钳stu当die割sb雁egi芽nni盖ng哑in伸the劈燕19赛70s迈ha窗ve砖sho芳wn司tha蛾tb遣eta贵-bl旱ock存ers律ca词ni桨mpr刘ove省sy畜mpt镜oms阔an旅dv狡ent蜡ric抖ula锈rf浆unc牌tio肿ni悼np趋ati寄ent幕sw捏ith麦mo疲der提ate悉to贿se论ver训eh苹ear铲tf铺ail身ure话,a售nd委may雁sl屠ow们the井pr哄ogr置ess溪ion文of英he旬art怜fa医ilu龟re吉in葡som后ep石ati扯ent循s(泽rev页iew胆ed跪in禾Bri革sto危w,句Cir管cul础ati衣on惕101锁:55埋8(贩200桶0))Tho刺ugh换be贷ta-畅blo纳cke某rs竞wer励ew世ide川ly巷con衣sid阶ere快dt距ob帽ec岩ont帮rai藏ndi桨cat哀ed歇for腐pa岁tie教nts免wi进th吩hea返rt摄fai瞒lur般eo境nly答a娇dec拨ade继ag寇o,沃the队ya滑re渴now汪co紧nsi递der蹄edfir孙st-摧lin抽et腾her尼apy晋fo冠rp棒ati锣ent吉sw顿ith差mi挪ld考to竞mod诉era伯te盆hea腾rt侦fai涌lur哥e现认为脂姥溶性的效市果更好。met朴opr奸olo斑lcarv翁edil孙olbis袋opr惕olo挑lThe躲ad辆ver彩se轰eff职ect没s:w疗ors润eni外ng餐of纲sym示pto钢ms,帽hy谎pot果ens姥ion卫,a漠nd析bra逗dyc量ard诱iaThe知se守sym艺pto闻ms稠can副be押mi石nim美ize央db翻yi冰nit香iat猾ing清th垂era勉py嗽wit否hl若ow摘dos螺es购and蹦gr质adu带all微yi虹ncr星eas珠ing虹do哪sag检eu昆nti甩lt路ole波rab舱le折the头rap惧eut晚ic屠dos旅es坚are版re板ach滴edBeta姨-blo旅cker糊sar元eco玻ntra舰indi贝cate愁din沈pat刊ient层swi挂tha误sthm铜aor箱sev和ere叨brad盒ycar登diaDiur膛etic召sMost纷pat始eint霸swi帜thh毒eart阵fai誉lure菜req犯uire污tre显atme贝ntw饰ith款diur游etic缩慧sto析rel门ieve薯sym橡ptom纠sof馒flu省idr找eten畏tion防(ed坚ema绪and挥cong怒esti捞on),战but塑the能iri盏sno雀evi帅denc商eth多atd碎iure历tics思slo日wth部epr惨ogre水ssio老nof瞎the喜dis菊ease渣or谷decr茫ease予mor锋tali清ty.Loop等diu叼reti替cs(决furo赏semi件de)律are筑the脱most誉eff欢ecti流ved那iure研tics多用于严妥重水钠潴盘留和肾功兄能不全时召。Thia苹zide斯diu捡reti卷csact涛ont舒hed远ista夫llo机opa岁nda许rel贴ess筛effe定ctiv票eth磨anl俩oop蹲diur者etic画s用于轻度倒水钠潴留骆。Con将cur能ren衔tu婶se跳of匪two劝di娃ure炕tic素sw御ith骆di邀ffe时ren只ts勇ite遇so畜fa蚁cti址on现may俗be装ne低ede音di以np安ati爸ent罪sw傅ho捆do惯not苗re递spo掉nd越wel稍lt兄oa北si罢ngl说eo画ral动di痒ure扒ticThe笛mo住st字com传mon田ad殊ver善se津eff替ect满of帐di山ure岛tic府th厅era仪py龙is炉pot筒ass焰ium卫de气ple农tio画nw雀hic匀hc虚an罢be蛮pre聪ven恢ted职by害us羞eo震fs焦upp兆lem丢ent面al骗pot盛ass斜ium嘱,a掀nA葵CE老inh株ibi税tor父,o锣ra滴po捎tas累siu雅m-s伞par绳ing拴di井ure工tic倾(s剪pir臣ono筐lac链ton坝eo省ra筹mil著ori档de)Ald掉ost分ero西ne席Ant围ago跌nis雅tsRec感ent湖cl黄ini抱cal钥tr遗ial绪si曾ndi寒cat粥et除hat结ad金din析gs责pir温ono有lac膝ton筛e(螺内酯)to价stan扯dard樱tre党atme佩ntc壮ans饭igni丙fica贸ntly辛dec浸reas宴emo泻rtal贵ity狸inp月atie南nts网with蚁sev麻ere背hear舌tfa健ilur产eEff戏ect冒ofspi羽ron柳ola春cto家neon腿sur辨viv圈al简in弃pat责ien透ts碌wit萍hm冠ode高rat究eo览rs炉eve计re扶con聪ges盒tiv头eh妹ear胜tf顽ail薪ure苦in央a贴ran诞dom绢ize负dd巴oub拆le-南bli遵nd馅cli节nic沫al者stu京dy.马(R呈epr扑odu窄ced桨,w钞ith它pe恐rmi最ssi际on,妄fr位om蜻Pit序tB氧et饲al困:T番he捡eff狗ect种of你sp布iro垦nol麦act孔one尺on剃mo梨rbi陵dit闪ya暖nd趣mor支tal挑ity科in止pa伶tie淋nts底wi熔th夏sev声ere欧he过art摩fa霸ilu佛re.蜡N钉Eng丑lJ糊Me烂d1凭999物;34捡1:7淡09醛固酮受古体拮抗剂垫螺内酯降低充我血性心幕衰病人秒死亡率Oth驾er递Age继nts君wi厕th宗The尸rap禾aeu晕tic犯Po存ten奖tia燃lEndo栽thel撑in-1夫Ant摇agon符istsThe冻va钞soc票ons鄙tri暴cto蝇rp铲ept键ide席,e鞠ndo抹the插lin衫-1,肿is滥kn白own辆to板be暑el器eva条ted晨in川he剪art地fa桐ilu申re宅and秘is叫a假pre拨dic晶tor烂of衰mo题rta航lit垮yi量np锡ati注ent赞sw争ith穗he箱art峰fa便ilu装re.察An那ima夜lm尸ode柏ls弟of羽hea唐rt洒fai石lur贯ei件ndi币cat附ee辟ndo歪the躁lin具re行cep弊tor垒an嘱tag数oni劲sts顶su述ch著as左bos末ent界an冤may著ha承ve气lon辞g-t啄erm息be鸽nef醒its胶in铁re业ver耀sin象gm在yoc星ard冠ial悠re誉mod出eli独ng灾and慕im厉pro确vin引gs钞urv插iva忧l.炭Sho海rt-烈ter耕m,染sma奔ll-际sca授le促tri格als土in肯hu钞man予si呜ndi登cat提ep滔oss泥ibl济eb比ene填fic内ial蚁ef俘fec察ts幸on股sys望tem觉ic尿and睁pu卵lmo来nar摧yh金emo随dyn驱ami甩csxan械thi奇ne鉴oxi屿das程ei形nhi言bit乳orBack典grou易nd:Hig辫hs蚕eru荣mu斩ric短ac密id奋(SU冷A)赵lev乖els圾ar原ea挪st闪ron倒g,蒜ind放epe哄nde啄nt擦mar例ker眼of散im询pai蛛red土pr荡ogn疑osi汇si严np君ati外ent泪sw亮ith芦mo珍der虎ate艇to歼se淘ver猎eC朴HF.Resu泼lts锻and铺conc惑lusi伪on:Oxyp竞urin维old轮idn约otp社rod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