治療充血性心力衰竭藥物

DrugsforCongestiveHeartFailure

心力衰竭（heartfailure）是各種原因引起的心肌舒縮障礙，導(dǎo)致心輸出量不能滿足機體需求的一組臨床綜合征。充血性心衰是其中最主要的一種。 慢性或充血性心力衰竭（congestiveheartfailure,CHF）是各種病因所引起的多種心臟疾?。ü谛摹⒏咝摹⒎涡?、風(fēng)心、心肌病等）的終末階段，當(dāng)靜脈回流足夠的情況下，心臟排出量絕對或相對減少，不能滿足機體組織需求的一種臨床或病理綜合征。心衰病人運動耐量下降，壽命縮短。Concept: CHFisacomplexclinicalsyndromecharacterizedbyimpairedventricularperformance,exerciseintolerance,ahighincidenceofventriculararrhythmias,andshortenedlifeexpectancyThesignsandsymptoms

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。心衰的分級（NYHA標(biāo)準(zhǔn)）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(yán)重代償不全，休息時亦有癥狀，不能從事任何體力活動。 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(dǎo)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(xì)胞增多 等幾方面的心臟外代償作用。 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(fù)擔(dān)。 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(fù)擔(dān)，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。神經(jīng)體液系統(tǒng)主要改變Increasedsympatheticnervoussystemactivity(andincreasedplasmacatecholamines,b-receptordownregulation)Increasedactivityoftherenin-angiotensin-aldosteronesystem

Increasedreleaseofarginine-vasopressin

心衰的一些代償機制Inadditiontotheeffectsshown,angiotensinIIincreasessympatheticeffectsbyfacilitatingnorepinephrinerelease.

慢性心衰的藥物治療：

應(yīng)減輕負(fù)荷，降低能耗，保護心臟。達(dá)到改善血流動力學(xué)；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(xué)指標(biāo)：壓力指標(biāo)：LVEDP，±dP/dtmax；容積指標(biāo)：SV，CO，CI，EF（正常0.67,心衰<0.45,嚴(yán)重心衰<0.3）時間指標(biāo)：PEP，LVET，T-dP/dtmax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Diureticspharmacologicintervention

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-blockerscandecreasemortalityConsensusrecommendationsforthemanagementofCHFPatientswithheartfailureshouldfirstbeevaluatedtoassessLVejectionfraction.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fluidretention-adiuretic.ACEinhibitorandbeta-blockershouldbeinitiatedandmaintainedunlessspecificallycontraindicated.（Patientswithsevereheartfailureshouldprobablynotreceiveabeta-blocker）Digoxin-inpatientswithrapidatrialfibrillation.Spironolactone,analdosteroneantagonist,mayreducemortalityinpatientswithsevereheartfailureACEinhibitorsfirst-linetherapyinallpatientswithheartfailure

improvesymptoms,slowprogressionofthedisease,reducemortality,anddecreasetheincidenceofhospitalizationThemostcommonadverseeffectsofACEinhibitorsaredirectlyrelatedtoloweringangiotensinIIconcentrations(hypotensionandrenalinsufficiency)andincreasingconcentrationsofkinins(coughandangioneuroticedema)血管緊張素原AngiotensinⅠ收縮血管腎素激肽原緩激肽↑降解失活A(yù)ngⅢACEACEIsAngⅡ

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分泌醛固酮NOPGI(-)ACE和ACEIs作用示意圖舒張血管Captopril第1個在臨床上廣泛應(yīng)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。ARBs-angiotensinreceptorblockersangiotensinreceptorantagonists(AT1ReceptorAntagonists)areaseffectiveasACEinhibitorsintreatingheartfailure,butitappearsthattherapeuticefficacymaybecomparablelosartan,candesartan,valsartanInotropicDrugs-digitalisThebeneficialeffectsofcardiacglycosidesinthetreatmentofheartfailurehavebeenattributedtoapositiveinotropiceffectonfailingmyocardiumandefficacyincontrollingtheventricularrateresponsetoatrialfibrillation.Thecardiacglycosidesalsomodulateautonomicnervoussystemactivity,anditislikelythatthismechanismcontributessubstantiallytotheirefficacyinthemanagementofheartfailure.Pos戴iti召ve捕Ino掉tro億pic服Ef級fec畝t（抑制Na+,含K+-A戀TPas沉e）Elec味trop讀hysi偏olog忠ical名Act臺ions（加上鬧增強迷殲走）Reg貼ula餃tio浴no趣fS翼ymp撓ath烘eti驢cN扭erv棄ous壟Sy染ste嫁mA瓜cti饅vit垮yTher考eis午evi門denc栽eth持atd障igit堤alis剪may貢act混dir賺ectl辟ytosen略sit黑iza壯tio拘no善fbaro咱rece里ptor紀(jì)res嚇pons恢ean抽dth關(guān)ereb憂yex永ert紹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請symp里athe虛tic哄toneThe攜rece斑ntD質(zhì)igit攪alis烈Inv針esti帽gati有onG食roup蛇(DI唱G)c盯lini游cal艙tria寸lin憂dica測ted艱digo倚xin蔑did插not笛redu偽ceo繭vera攏llm統(tǒng)orta腔lity乳in導(dǎo)pati圓ents掩wit叔hhe粒art特fail虛ure親(who挺wer芒ere乓ceiv耍ing僵diur粥etic區(qū)san盜dAC毫Ein溜hibi紙tors膀),b解utd蝴idr叛educ有eth痕era策teo住fho丟spit園aliz腐atio烤nOth蛙er隆ino間tro氧pic愚ag施ent勒s只適用于君急性心衰獸，長期應(yīng)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攪ne,熱pr糧ena螞lte殿rolLevo糕dopa汪and較ibo永pami撈neCycl魯icN刻ucle臨otid信ePh幟osph溉odie特ster蒙ase拒(PDE尊-III放,cG鴨MP-i潑nhib瓦itab互leP典DE)縮慧Inhi頁bito宇rsBipy敵ridi怠nes-視amr缸inon梳ean幸dmi怠lrin咱oneimi松daz懸olo遺ne砍der傭iva踐tiv六es-于en充oxi半mon消ea疲nd豎pir型oxi枯mon寒eBet呢a-B濤loc犯ker從sa便nd脂CHFAn效umb爛er與of鉗stu當(dāng)die割sb雁egi芽nni蓋ng啞in伸the劈燕19賽70s邁ha窗ve磚sho芳wn司tha蛾tb遣eta貴-bl旱ock存ers律ca詞ni槳mpr劉ove省sy畜mpt鏡oms闊an旅dv狡ent蠟ric抖ula銹rf漿unc牌tio腫ni悼np趨ati寄ent幕sw捏ith麥mo疲der提ate悉to賄se論ver訓(xùn)eh蘋ear鏟tf鋪ail身ure話,a售nd委may雁sl屠ow們the井pr哄ogr置ess溪ion文of英he旬a(chǎn)rt憐fa醫(yī)ilu龜re吉in葡som后ep石ati扯ent循s(澤rev頁iew膽ed跪in禾Bri革sto危w,句Cir管cul礎(chǔ)ati衣on惕101鎖:55埋8(販200桶0))Tho刺ugh換be貸ta-暢blo納cke某rs競wer勵ew世ide川ly巷con衣sid階ere快dt距ob帽ec巖ont幫rai藏ndi槳cat哀ed歇for腐pa歲tie教nts免wi進th吩hea返rt攝fai瞞lur般eo境nly答a嬌dec撥ade繼ag寇o,沃the隊ya滑re渴now汪co緊nsi遞der蹄edfir孫st-摧lin抽et騰her尼apy晉fo冠rp棒ati鑼ent吉sw頓ith差mi挪ld考to競mod訴era伯te盆hea騰rt偵fai涌lur哥e現(xiàn)認(rèn)為脂姥溶性的效市果更好。met樸opr奸olo斑lcarv翁edil孫olbis袋opr惕olo挑lThe躲ad輛ver彩se轟eff職ect沒s:w療ors潤eni外ng餐of綱sym示pto鋼ms,帽hy謊pot果ens姥ion衛(wèi),a漠nd析bra逗dyc量ard誘iaThe知se守sym藝pto聞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購and蹦gr質(zhì)adu帶all微yi虹ncr星eas珠ing虹do哪sag檢eu昆nti甩lt路ole波rab艙le折the頭rap懼eut晚ic屠dos旅es堅are版re板ach滴edBeta姨-blo旅cker糊sar元eco玻ntra艦indi貝cate愁din沈pat刊ient層swi掛tha誤sthm銅aor箱sev和ere叨brad盒ycar登diaDiur膛etic召sMost紛pat始eint霸swi幟thh毒eart陣fai譽lure菜req犯uire污tre顯atme貝ntw飾ith款diur游etic縮慧sto析rel門ieve薯sym橡ptom糾sof饅flu省idr找eten畏tion防(ed堅ema緒and揮cong怒esti撈on),戰(zhàn)but塑the能iri盞sno雀evi帥denc商eth多atd碎iure歷tics思slo日wth部epr慘ogre水ssio老nof瞎the喜dis菊ease渣or谷decr茫ease予mor鋒tali清ty.Loop等diu叼reti替cs(決furo賞semi件de)律are筑the脫most譽eff歡ecti流ved那iure研tics多用于嚴(yán)妥重水鈉潴盤留和腎功兄能不全時召。Thia蘋zide斯diu撿reti卷csact濤ont舒hed遠(yuǎn)ista夫llo機opa歲nda許rel貼ess篩effe定ctiv票eth磨anl倆oop蹲diur者etic畫s用于輕度倒水鈉潴留駱。Con將cur能ren銜tu嬸se跳of匪two勸di娃ure炕tic素sw御ith駱di邀ffe時ren只ts勇ite遇so畜fa蟻cti址on現(xiàn)may俗be裝ne低ede音di以np安ati爸ent罪sw傅ho捆do慣not苗re遞spo掉nd越wel稍lt兄oa北si罷ngl說eo畫ral動di癢ure扒ticThe笛mo住st字com傳mon田ad殊ver善se津eff替ect滿of帳di山ure島tic府th廳era儀py龍is爐pot筒ass焰ium衛(wèi)de氣ple農(nóng)tio畫nw雀hic勻hc虛an罷be蠻pre聰ven恢ted職by害us羞eo震fs焦upp兆lem丟ent面al騙pot盛ass斜ium囑,a掀nA葵CE老inh株ibi稅tor父,o鑼ra滴po捎tas累siu雅m-s傘par繩ing拴di井ure工tic傾(s剪pir臣o(jì)no筐lac鏈ton壩eo省ra籌mil著ori檔de)Ald掉ost分ero西ne席Ant圍ago跌nis雅tsRec感ent湖cl黃ini抱cal鑰tr遺ial緒si曾ndi寒cat粥et除hat結(jié)ad金din析gs責(zé)pir溫ono有l(wèi)ac膝ton篩e(螺內(nèi)酯)to價stan扯dard櫻tre黨atme佩ntc壯ans飯igni丙fica貿(mào)ntly辛dec浸reas宴emo瀉rtal貴ity貍inp月atie南nts網(wǎng)with蟻sev麻ere背hear舌tfa健ilur產(chǎn)eEff戲ect冒ofspi羽ron柳ola春cto家neon腿sur辨viv圈al簡in棄pat責(zé)ien透ts碌wit萍hm冠ode高rat究eo覽rs爐eve計re扶con聰ges盒tiv頭eh妹ear勝tf頑ail薪ure苦in央a貼ran誕dom絹ize負(fù)dd巴oub拆le-南bli遵nd餡cli節(jié)nic沫al者stu京dy.馬(R呈epr撲odu窄ced槳,w鈔ith它pe恐rmi最ssi際on,妄fr位om蜻Pit序tB氧et飼al困:T番he撿eff狗ect種of你sp布iro墾nol麥act孔one尺on剃mo梨rbi陵dit閃ya暖nd趣mor支tal挑ity科in止pa伶tie淋nts底wi熔th夏sev聲ere歐he過art摩fa霸ilu佛re.蠟N釘Eng丑lJ糊Me爛d1憑999物;34撿1:7淡09醛固酮受古體拮抗劑墊螺內(nèi)酯降低充我血性心幕衰病人秒死亡率Oth駕er遞Age繼nts君wi廁th宗The尸rap禾aeu暈tic犯Po存ten獎tia燃lEndo栽thel撐in-1夫Ant搖agon符istsThe凍va鈔soc票ons鄙tri暴cto蠅rp鏟ept鍵ide席,e鞠ndo抹the插lin衫-1,腫is濫kn白own輛to板be暑el器eva條ted晨in川he剪art地fa桐ilu申re宅and秘is叫a假pre撥dic晶tor爛of衰mo題rta航lit垮yi量np錫ati注ent贊sw爭ith穗he箱art峰fa便ilu裝re.察An那ima夜lm尸ode柏ls弟of羽hea唐rt灑fai石lur貫ei件ndi幣cat附ee辟ndo歪t(yī)he躁lin具re行cep弊tor壘an囑tag數(shù)oni勁sts頂su述ch著as左bos末ent界an冤may著ha承ve氣lon辭g-t啄erm息be鴿nef醒its膠in鐵re業(yè)ver耀sin象gm在yoc星ard冠ial悠re譽mod出eli獨ng災(zāi)and慕im厲pro確vin引gs鈔urv插iva憂l.炭Sho海rt-烈ter耕m,染sma奔ll-際sca授le促tri格als土in肯hu鈔man予si嗚ndi登cat提ep滔oss泥ibl濟eb比ene填fic內(nèi)ial蟻ef俘fec察ts幸on股sys望tem覺ic尿and睜pu卵lmo來nar摧yh金emo隨dyn驅(qū)ami甩csxan械thi奇ne鑒oxi嶼das程ei形nhi言bit乳orBack典gr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