最新心力衰竭知识PPT课件.ppt

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1、心力衰竭知识心力衰竭知识Chronic or Congestive Heart Failure，CHFCHFoccurswhenthecardiacoutputisinadequatetoprovidetheoxygenneededbythebody.ThekeydefectinCHFisadecrease in cardiac contractility,resultingininadequatecardiacoutputClassification of drugs used in CHF1.Renin-angiotensin-aldosteronesysteminhibitors(1)A

2、CEIcaptopril(2)angreceptorblocker(AT1antagonist)losartan(3)aldosteroneantagonistspironolacton2.Diureticsthiazides,furosemide3.-receptor blockerMetoprolol,carvedilol4.positive inotropic agents(1)Cardiacglycosidesdigoxin,digitoxin(2)non-glycosidepositiveinotropicagentsmilrinone5.vasodilators nitroprus

3、sidesodium6.calcium sensitizer and calcium channel blockersamlodipineSectionIIInhibitorsofrenin-angiotensin-aldosteronesystem(RAAS)Renin-AngiotensinSystem(RAS)angiotensinogenreninAngiotensin糜酶旁路糜酶旁路ACEAngiotensinAT1receptor1.vasoconstriction,aldosterone：BP2.hypertrophyandproliferationcardiovascularr

4、emodelingKallikrein-KininSystem(KKS)kininogenase Bradykinin 降解产物降解产物AT2receptorNO,partfightAT1receptorVasodilation,BPACEI()ThecompositionandphysiologicalroleofRASAT1Blockerspironolactone angiotensin-converting enzyme inhibitor，ACEI:captopril,enalapril angiotensin receptor(AT1)blocker,ARB:losartan氯沙坦

5、氯沙坦 antagonist for the aldosterone receptor:spironolactoneThe classification of Inhibitors RAAS1.ACEI卡托普利（卡托普利（captopril）（开搏通）（开搏通）依那普利（依那普利（enalapril）（悦宁定）（悦宁定）赖诺普利（赖诺普利（lisinopril）（帝益洛）（帝益洛）苯那普利（苯那普利（benazepril （洛丁新（洛丁新/诺华）诺华）福辛普利（福辛普利（fosinopril）（蒙诺（蒙诺/施贵宝）施贵宝）喹那普利（喹那普利（quinapril）（益恒）（益恒）雷米普利（雷米普

6、利（ramipril）（瑞泰）（瑞泰）培哚普利（培哚普利（perindopril）（雅施达）（雅施达）西拉普利（西拉普利（cilazapril）（一平苏）（一平苏）药药 物物起始剂量起始剂量目标剂量目标剂量卡托普利6.25 mg，tid50 mg，tid依那普利2.5 mg，bid1020 mg，bid福辛普利510 mg/d 40 mg/d赖诺普利2.55 mg/d 3035 mg/d培哚普利2 mg/d48 mg/d喹那普利5 mg，bid20 mg，bid雷米普利2.5 mg/d5 mg，bid 或10 mg/d西拉普利0.5 mg/d12.5 mg/d苯那普利2.5 mg/d510 m

7、g，bid治疗慢性心衰的ACEI及其剂量The mechanism for anti-congestive heart failure effect1.peripheral vascular resistance,cardiac afterload 2.aldosterone 3.myocardial and ventricular remodeling4.changes of hemodynamics 5.the activity of sympathetic nervous systemACEI1.peripheral vascular 1.peripheral vascular resi

8、stance,cardiac afterloadresistance,cardiac afterloadACEI内皮衍生超极化因子内皮衍生超极化因子(Endothelium Derived Hyperpolarizing Factor)5.antisympathetic effectvAT1 receptor in presynaptic membrane of sympathetic nerve NA vAT1 receptor in adrenal medella NA vAT1 receptor in CNScentral sympathetic impulse transmission

9、 heart load and damageACEI1)Thesaltandwaterretention2)Thepreloadandafterload3)Thelong-termremodelingoftheheartandvesselsMortalityandmorbidityTherapeuticapplicationsCHFHypertensionClinical using:ACEIAT1blocker,ARB氯沙坦氯沙坦(losartan)(losartan)缬沙坦缬沙坦(valsartan)(valsartan)厄贝沙坦厄贝沙坦(irbesartan)(irbesartan)坎地

10、沙坦坎地沙坦(candesartan)(candesartan)依普沙坦依普沙坦(eprosartan)(eprosartan)替米沙坦替米沙坦(telmisartan)(telmisartan)Renin-AngiotensinSystem(RAS)angiotensinogenreninAngiotensin糜酶旁路糜酶旁路ACEAngiotensinAT1receptor1.vasoconstriction,aldosterone：BP2.hypertrophyandproliferationcardiovascularremodelingKallikrein-KininSystem(K

11、KS)kininogenase Bradykinin 降解产物降解产物AT2receptorNO,partfightAT1receptorVasodilation,BPThecompositionandphysiologicalroleofRASARBSectionIIIDiureticsHigh-efficacy diuretics(loop diuretics)FurosemideModerate-efficacy diuretics Thiazides;Low-efficacy diureticsSpironolactone；vTheycanpromotethelossofsodiuma

12、ndwaterfromthebodyandprovideareductioninpreloadandafterload.Cardiogenic edema relievethesymptomsmildCHFThiazidesmoderateCHFThiazides+SpironolactoneIfitfailsorfortheseriousCHFloopdiuretics；ButCautions:Alargedosediureticscardiacoutput;sympatheticnerveactivityaldosteroneandhypokalemia.Coadministrationw

13、ithspironolactone Diuretics SectionIV-receptorblocker1.Drugsactingon-receptor(1)Carvedilol,-receptorblocker.(2)Metoprolol 1-receptorblockerPharmacologicaleffectsInhibition of sympathetic activity catecholaminesCa2+infux myocardial necrosismyocardial remodelingreninangiotensinup-regulating R sensitiv

14、ity of R to catecholaminesAnti-arrhythmic and anti-ischemic effects-R blockerTherapeuticapplicationsMildandmoderateCHFDilatedcardiomyopathy心肌病CHF,ischemicCHFImprovesymptomsanddecreasemortalityCombinationwithdiureticsandACEIThemedicationshouldbeinitiatedwithlowdoses.-R blockerBronchospasm,bradycardia

15、andhypotensionOthers:depression,nightmares,fatigue,andsexualdysfunction;asthma;maskinghypoglycemicsymptomsAdverseEffects-R blockerClassification of drugs used in CHF1.Renin-angiotensin-aldosteronesysteminhibitors(1)ACEIcaptopril(2)angreceptorblocker(AT1antagonist)losartan(3)aldosteroneantagonistspir

16、onolacton2.Diureticsthiazides,furosemide3.-receptor blockerMetoprolol,carvedilol4.positive inotropic agents(1)Cardiacglycosidesdigoxin,digitoxin(2)non-glycosidepositiveinotropicagentsmilrinone5.vasodilators nitroprussidesodium6.calcium sensitizer and calcium channel blockersamlodipineHeartfailureRed

17、ucedcardiacoutputSympatheticnervoussystemactivationVasoconstrictionElevatedcardiacfillingpressureSodiumandwaterretentionAngiotensinReninCardiacremodelingAldosteroneAngiotensinPathophysiologicalmechanismsofheartfailureandmajorsitesofdrugactiondigoxin-blockers,digoxinVasodilatorsACEinhibitorsAngiotens

18、in-RblockersDiureticsSpironolactoneDigitoxin 洋地黄毒苷洋地黄毒苷Digoxin 地高地高辛辛 Deslanoside 毛花毛花苷丙苷丙Strophantin K 毒毛花苷毒毛花苷K KSection V Cardiac glycosides甾核甾核Steroid不饱和不饱和内酯环内酯环Lactonering三分子洋地黄毒三分子洋地黄毒糖糖 tri-digitoxose(苷元的作用强度和时间）苷元的作用强度和时间）Chemical structure of Digoxin 苷元苷元aglycone(正性肌力正性肌力)（C3、C14)OH；C17具具构

19、型。否则苷构型。否则苷元失去强心作元失去强心作用。用。OOOOHOHCH3HCH3HC18H31O53 314141717BACDEffects of cardiac glycosides on heart(ahighlyselectiveforheart)1.Positive inotropic action(1)Cardiac glycosides themaximumforcethecontractilityofcardiacmusclethe velocityofcardiacmusclecontractiondiastolerelativeextension 强强 心心 苷苷Anti

20、-congestiveheartfailuredrugsCHFpatients:Cardiacglycosidescardiac outputcardiacfillingpressuresheartsizeandvenousandcapillarypressures.(2)Cardiac output 强强 心心 苷苷Anti-congestiveheartfailuredrugsa.In normal individuals:contractilitymyocardialminuteoxygenconsumption(MVO2).b.In patients with CHF:ventricu

21、larvolumeMVO2.(3)Myocardial oxygen consumption 强强 心心 苷苷Anti-congestiveheartfailuredrugsMyocardial oxygen consumptionventricular pressure(afterload)ventricular volume(preload)contractility heart rate ventricular wall tension O2 demand 强强 心心 苷苷Anti-congestiveheartfailuredrugsInhibitthemembrane-boundNa

22、+-K+-ATPase.InhibitionofNa+-K+-ATPaseresultsinintracellularaccumulationofNa+(andlossofintracellularK+).AccumulationofintracellularNa+slightmovementofextracellularCa2+intothecellsecondarytoactivationofamembraneNa+-Ca2+carrier.The mechanism for positive inotropic effect Digoxinmayinterferewiththeabili

23、tyofthesarcoplasmicreticulumtobindCa2+makingmoreCa2+availableforinteractionwithcontractileproteinsCa2+positive inotropic effect说教学过程说教学过程Na+Ca2+K+intracellularextracellularNKANCE 强强 心心 苷苷 Anti-congestiveheartfailuredrugsNKA:Na+-K+-ATPaseNCE:Na+-Ca2+exchangerThe mechanism for positive inotropic effec

24、t说教学过程说教学过程 强强 心心 苷苷Anti-congestiveheartfailuredrugsCICR:Calcium induced calcium releaseCa2+Ca2+i与与AP和心肌收缩的关系和心肌收缩的关系The mechanism for positive inotropic effectThe mechanism for positive inotropic effectCardiac glycosidesMLCK:Myosin light chain kinase肌球蛋白肌球蛋白轻链轻链激激酶酶SERCA:Sarco-endoplasmic Reticulum

25、 Calcium Atpase肌肌浆浆网网钙泵钙泵SOCE:store-operated calcium entry channels钙钙池操池操纵钙纵钙离子通道离子通道RYR:Ryanodine receptor兰兰尼碱受体尼碱受体 强强 心心 苷苷Anti-congestiveheartfailuredrugs 强心苷强心苷 Na+-K+-ATPase Na+-K+交换交换Cell内内Na+短暂短暂 C内内Na+超负荷，超负荷，失失K+影响影响Na+-Ca2+交换机制交换机制 Ca2+超负荷超负荷 异位节律点异位节律点 自律性自律性 Na+外流外流，Ca2+内流内流 迟后去极迟后去极Na+

26、内流内流，Ca2+外流外流 C内内Ca2+i 心律失常心律失常 正性肌力正性肌力治疗量治疗量中毒量中毒量CICRCICR:Calcium induced calcium release说教法说教法HRMechanism：A A：COCOactivating vagus nerve B B：sensitivity of vagusSignificance：负性频率负性频率心动周期心动周期舒张期舒张期 心室充盈好心室充盈好 心肌自身供血心肌自身供血 心肌获充分休息心肌获充分休息心功能改善心功能改善Effects of cardiac glycosides on heart2.Negative ch

27、ronotropic action 强强 心心 苷苷Anti-congestiveheartfailuredrugs窦房结自律性窦房结自律性房室传导房室传导心房心房ERPERP浦肯野纤维自律性，浦肯野纤维自律性，ERPERP、传导、传导与增加迷走神经活性有关与增加迷走神经活性有关3.Electrophysiological effects抑制抑制Na+-K+-ATP酶酶0-50If,Ik and Na+-Ca2+exchangeCa2+channelK+channel增加迷走神经活性增加迷走神经活性vCaCa2+2+内流内流房室传导房室传导房扑转为房颤房扑转为房颤a.therapeutic d

28、ose3.Electrophysiological effects 强强 心心 苷苷Anti-congestiveheartfailurev窦房结细胞窦房结细胞KAch开放频率开放频率K+外流外流静息期膜电静息期膜电位位（多负）（多负）自律性自律性窦性频率窦性频率vKK+外流外流心房心房ERPERP缩短缩短0-50If,Ik and Na+-Ca2+exchangeCa2+channelK+channel 促促K+外流外流 心房肌静息电位加大心房肌静息电位加大 零相除极速度零相除极速度 心心房传导速度房传导速度()Na()Na+-K-K+-ATP-ATP酶酶KK+ii最大舒张电位最大舒张电位（

29、少负）（少负）接近阈电位接近阈电位自律性自律性；c.toxic doseb.high dose（提高普氏纤维自律性）（提高普氏纤维自律性）CentralsympatheticactivityCaCa2+2+ii；ERPERP（中毒时室速或室颤的机制中毒时室速或室颤的机制）强强 心心 苷苷Anti-congestiveheartfailuredrugsK+外流ERP最大舒最大舒张电张电位位除极除极发发生在生在较较小的膜小的膜电电位位 强强 心心 苷苷Anti-congestiveheartfailuredrugs电生理电生理 特性特性窦房结窦房结心房心房房室结房室结浦肯野浦肯野纤维纤维自律性自律

30、性传导性传导性ERPERP与增加迷走神经活性有关与增加迷走神经活性有关抑制抑制Na+-K+-ATP酶酶是强心苷引起室早、室是强心苷引起室早、室性心律失常的原因之一性心律失常的原因之一治疗房颤、房扑治疗房颤、房扑使房扑转为房颤使房扑转为房颤3.Electrophysiological effectsWithmoretoxicconcentration,restingmembranepotentialisreducedasaresultofinhibitionofthesodiumpumpandreducedintracellularpotassium.Glycosidestoxicity:atr

31、ioventricularjunctionalrhythm,prematureventriculardepolarization,bigeminalrhythm,andatrioventricularblockade.3.Electrophysiological effectsRegulation of neuroendocrine activity=-Parasympathomimetic effectsAtlowerdose:mainlyaffectsatrialandatrioventricularnodalfunction.=-Sympathomimetic effectsAtover

32、dose,enhancetheactivityofsympatheticnervouscentre.Anorexia厌食,nauseaandvomiting,headache,fatigue,.=-RAASreninactivity;Ag;aldosterone 强强 心心 苷苷Anti-congestiveheartfailuredrugs1)EffectsonvascularInnormalindividuals:peripheralvascularresistance(directaction)InpatientswithCHF:peripheralvascularresistance(

33、indirectaction)2)EffectsonkidneyAdiureticeffect.cardiacfunctionimprovementinhibitionofkidneytubularNa+-K+-ATPaseExtracardiac effects 强强 心心 苷苷Anti-congestiveheartfailuredrugsPharmacokineticsSerumPrincipalAbsorptionProteinTherapeuticMetabolicDrugs(Peros)BindingT1/2ConcentrationRouteDigoxin6085%25%36h0

34、.52.0ngKidneyDigitoxin90100%97%57d1035ng/mlLiver 强强 心心 苷苷Anti-congestiveheartfailuredrugsTherapeutic usesCHF 强强 心心 苷苷Anti-congestiveheartfailuredrugs2.Arrhythmias:1.1.心房纤颤心房纤颤：350-600次/分（f波）强心苷强心苷迷走兴奋迷走兴奋房室传导房室传导 房室结隐匿性传导房室结隐匿性传导心室率心室率 2.2.心房扑动心房扑动：240-430次/分（F波）强心苷强心苷心房心房ERPERP扑动变颤动扑动变颤动心室率心室率；有些病人

35、在停用强心苷后可恢复为窦性节律有些病人在停用强心苷后可恢复为窦性节律 3.3.阵发性室上性心动过速阵发性室上性心动过速：迷走兴奋迷走兴奋（现已少用)房扑房扑房颤房颤fff 强强 心心 苷苷Anti-congestiveheartfailuredrugsDrug actions and doses1.Action vs Effect or Response2.Pharmacological effects and doseslethallethaltoxic toxic max.effectivemax.effectivemin.effective min.effective submedica

36、lsubmedicalTherapeutic or Therapeutic or medical dosemedical doseUntoward effects(1)Cardiaceffects(a)Prematureventricularbeatsandventriculartachycardiaandfibrillation(b)A-Vblock(c)Sinusbradycardia(3ng/ml,3ng/ml,洋洋 地地 黄黄 毒毒 苷苷45ng/ml 45ng/ml -停药停药;3.3.注意药物相互作用注意药物相互作用：排钾利尿药：排钾利尿药：低血钾低血钾 加重毒性，注意补钾；加重毒

37、性，注意补钾；钙钙阻阻滞滞剂剂、胺胺碘碘酮酮、普普罗罗帕帕酮酮抑抑制制地地高高辛辛经经肾肾小小管分泌管分泌减量；减量；奎尼丁奎尼丁能自组织置换地高辛能自组织置换地高辛 肝药酶诱导剂肝药酶诱导剂 苯妥英钠苯妥英钠-清除清除-血药浓度血药浓度 拟肾上腺素药拟肾上腺素药-心肌对强心苷敏感性心肌对强心苷敏感性【中毒预防措施】【中毒预防措施】强强 心心 苷苷Anti-congestiveheartfailuredrugsNon-Cardioglycoside Positive Inotropic Drugs1.PDEinhibitors.cAMPCa2+apositiveinotropiceffectv

38、asodilation:directaction1)Milrinone米力农2)Vesnarinone维司力农Theyhavenotbeenshowntoreducesurvivalinplacebo-controlledtrials.2.1-selective adrenoceptor agonistDobutamine多巴酚丁胺Ibopamine异布帕明IncreasemortalityNotforregularuseinCHFSection VI VasodilatorsZEffectiveinCHFbecausetheyprovideareductioninpreload,orredu

39、ctioninafterload,orboth.ZNitroprusside sodium:rapidafterloaddecrease,acutesevereCHF.3.Calcium channel blokersAmlodipineFelodipineTheyareeffectivearterialvasodilatorsandreducetheafterloadofheart.ReduceHR,facilitatingdiastolicrelaxationandloweringdiastolicfillingpressures.NotforroutineuseinCHF.PDEIPDEI利尿药利尿药心力衰竭治疗建议概要（心力衰竭治疗建议概要（2002）不同心功能分级心力衰竭患者的治疗不同心功能分级心力衰竭患者的治疗NYHA心功能心功能级：级：控制危险因素；控制危险因素；ACEI。NYHA心心功功能能级级：ACEI；利利尿尿剂剂；-R阻阻滞滞剂剂；地地高辛高辛用或不用。用或不用。NYHA心心功功能能级级：ACEI；利利尿尿剂剂；-R阻阻滞滞剂剂；地地高辛高辛。NYHA心心功功能能级级：ACEI；利利尿尿剂剂；地地高高辛辛；醛醛固固酮酮受体拮抗剂受体拮抗剂；病情稳定者，谨慎应用；病情稳定者，谨慎应用-R阻滞剂阻滞剂。Thank you!Thank you!3