最新心力衰竭知识ppt课件PPT文档.ppt

Chronic or Congestive Heart Failure，CHF,CHF occurs when the cardiac output is inadequate to provide the oxygen needed by the body.The key defect in CHF is a decrease in cardiac contractility,resulting in inadequate cardiac output,The Causes of Heart Failure,The characterizations of CHF,Decrease in cardiac contractility,inadequate cardiac output.Intravascular volume expansion and ventricular filling pressures,systemic and pulmonary hypertentension,dyspnea呼吸困难.Activation of sympathetic nervous and RASMyocardial dysfunction.Ventricular remodeling.,Ventricular remodeling after acute infarction,Ventricular remodeling in diastolic舒张 and systolic收缩 heart failure,Initial infarct,Expansion of infarct(hours to days),Global remodeling(days to months),Normal heart,Hypertrophied heart(diastolic heart failure),Dilated heart(systolic heart failure),Myocardial remodeling in Calcineurin transgenic hearts(Cell,Vol 93,215-228,1998),Heart failure,Reduced cardiac output,Sympathetic nervous system activation,Vasoconstriction,Elevated cardiac filling pressure,Sodium and water retention,Angiotensin,Renin,Cardiac remodeling,Aldosterone,Angiotensin,Pathophysiological mechanisms of heart failure and major sites of drug action,digoxin,-blockers,digoxin,Vasodilators,ACE inhibitors,Diuretics,Spironolactone,Classification of drugs used in CHF,1.Renin-angiotensin-aldosterone system inhibitors(1)ACEI captopril(2)ang receptor blocker(AT1 antagonist)losartan(3)aldosterone antagonist spironolacton2.Diuretics thiazides,furosemide3.-receptor blocker Metoprolol,carvedilol4.positive inotropic agents(1)Cardiac glycosides digoxin,digitoxin(2)non-glycoside positive inotropic agents milrinone5.vasodilators nitroprusside sodium6.calcium sensitizer and calcium channel blockers amlodipine,Section IIInhibitors of renin-angiotensin-aldosterone system(RAAS),Renin-AngiotensinSystem(RAS),angiotensinogen,renin,Angiotensin,糜酶旁路,ACE,Angiotensin,AT1receptor,1.vasoconstriction,aldosterone：BP2.hypertrophyandproliferation cardiovascularremodeling,Kallikrein-KininSystem(KKS),kininogenase,Bradykinin,降解产物,AT2receptor,NO,part fight AT1receptor,Vasodilation,BP,ACEI,(),The composition and physiologicalrole of RAS,AT1 Blocker,spironolactone,angiotensin-converting enzyme inhibitor，ACEI:captopril,enalapril angiotensin receptor(AT1)blocker,ARB:losartan氯沙坦 antagonist for the aldosterone receptor:spironolactone,The classification of Inhibitors RAAS,1.ACEI,卡托普利（captopril）（开搏通）依那普利（enalapril）（悦宁定）赖诺普利（lisinopril）（帝益洛）苯那普利（benazepril（洛丁新/诺华）福辛普利（fosinopril）（蒙诺/施贵宝）喹那普利（quinapril）（益恒）雷米普利（ramipril）（瑞泰）培哚普利（perindopril）（雅施达）西拉普利（cilazapril）（一平苏）,治疗慢性心衰的ACEI及其剂量,The mechanism for anti-congestive heart failure effect,1.peripheral vascular resistance,cardiac afterload 2.aldosterone 3.myocardial and ventricular remodeling4.changes of hemodynamics 5.the activity of sympathetic nervous system,ACEI,1.peripheral vascular resistance,cardiac afterload,ACEI,内皮衍生超极化因子(Endothelium Derived Hyperpolarizing Factor),5.antisympathetic effect,AT1 receptor in presynaptic membrane of sympathetic nerve NA AT1 receptor in adrenal medella NA AT1 receptor in CNScentral sympathetic impulse transmission heart load and damage,ACEI,1)The salt and water retention 2)The preload and afterload3)The long-term remodeling of the heart and vessels Mortality and morbidity,Therapeutic applications,CHFHypertension,Clinical using:,ACEI,AT1 blocker,ARB,氯沙坦(losartan)缬沙坦(valsartan)厄贝沙坦(irbesartan)坎地沙坦(candesartan)依普沙坦(eprosartan)替米沙坦(telmisartan),Renin-AngiotensinSystem(RAS),angiotensinogen,renin,Angiotensin,糜酶旁路,ACE,Angiotensin,AT1receptor,1.vasoconstriction,aldosterone：BP2.hypertrophyandproliferation cardiovascularremodeling,Kallikrein-KininSystem(KKS),kininogenase,Bradykinin,降解产物,AT2receptor,NO,part fight AT1receptor,Vasodilation,BP,The composition and physiologicalrole of RAS,ARB,Section III Diuretics,High-efficacy diuretics(loop diuretics)Furosemide Moderate-efficacy diuretics Thiazides;Low-efficacy diureticsSpironolactone；They can promote the loss of sodium and water from the body and provide a reduction in preload and afterload.,Cardiogenic edema relieve the symptoms mild CHF Thiazides moderate CHFThiazides+SpironolactoneIf it fails or for the serious CHFloop diuretics；But Cautions:A large dose diureticscardiac output;sympathetic nerve activityaldosterone and hypokalemia.Coadministration with spironolactone,Diuretics,Section IV-receptor blocker,1.Drugs acting on-receptor(1)Carvedilol,-receptor blocker.(2)Metoprolol1-receptor blocker,Pharmacological effects,Inhibition of sympathetic activity catecholaminesCa2+infux myocardial necrosismyocardial remodelingreninangiotensinup-regulating R sensitivity of R to catecholaminesAnti-arrhythmic and anti-ischemic effects,-R blocker,Therapeutic applications,Mild and moderate CHF Dilated cardiomyopathy心肌病 CHF,ischemic CHF Improve symptoms and decrease mortality Combination with diuretics and ACEI The medication should be initiated with low doses.,-R blocker,Bronchospasm,bradycardia and hypotensionOthers:depression,nightmares,fatigue,and sexual dysfunction;asthma;masking hypoglycemic symptoms,Adverse Effects,-R blocker,Classification of drugs used in CHF,1.Renin-angiotensin-aldosterone system inhibitors(1)ACEI captopril(2)ang receptor blocker(AT1 antagonist)losartan(3)aldosterone antagonist spironolacton2.Diuretics thiazides,furosemide3.-receptor blocker Metoprolol,carvedilol4.positive inotropic agents(1)Cardiac glycosides digoxin,digitoxin(2)non-glycoside positive inotropic agents milrinone5.vasodilators nitroprusside sodium6.calcium sensitizer and calcium channel blockers amlodipine,Heart failure,Reduced cardiac output,Sympathetic nervous system activation,Vasoconstriction,Elevated cardiac filling pressure,Sodium and water retention,Angiotensin,Renin,Cardiac remodeling,Aldosterone,Angiotensin,Pathophysiological mechanisms of heart failure and major sites of drug action,digoxin,-blockers,digoxin,Vasodilators,ACE inhibitors,Diuretics,Spironolactone,Digitoxin 洋地黄毒苷Digoxin 地高辛 Deslanoside 毛花苷丙Strophantin K 毒毛花苷K,Section V Cardiac glycosides,甾核Steroid,不饱和内酯环Lactone ring,三分子洋地黄毒糖 tri-digitoxose(苷元的作用强度和时间）,Chemical structure of Digoxin,苷元aglycone(正性肌力),（C3、C14)OH；C17具构型。否则苷元失去强心作用。,3,14,17,B,A,C,D,Effects of cardiac glycosides on heart(a highly selective for heart),1.Positive inotropic action(1)Cardiac glycosides the maximum force the contractility of cardiac muscle the velocity of cardiac muscle contraction diastole relative extension,CHF patients:Cardiac glycosides cardiac output cardiac filling pressures heart size and venous and capillary pressures.,(2)Cardiac output,In normal individuals:contractility myocardial minute oxygen consumption(MVO2).b.In patients with CHF:ventricular volume MVO2.,(3)Myocardial oxygen consumption,Myocardial oxygen consumption,ventricular pressure(afterload),ventricular volume(preload),contractility,heart rate,ventricular wall tension,O2 demand,Inhibit the membrane-bound Na+-K+-ATPase.Inhibition of Na+-K+-ATPase results in intracellular accumulation of Na+(and loss of intracellular K+).Accumulation of intracellular Na+slight movement of extracellular Ca2+into the cell secondary to activation of a membrane Na+-Ca2+carrier.,The mechanism for positive inotropic effect,Digoxin may interfere with the ability of the sarcoplasmic reticulum to bind Ca2+making more Ca2+available for interaction with contractile proteins Ca2+positive inotropic effect,说教学过程,Na+Ca2+K+,intracellular,extracellular,NKA,NCE,NKA:Na+-K+-ATPaseNCE:Na+-Ca2+exchanger,The mechanism for positive inotropic effect,说教学过程,CICR:Calcium induced calcium release,Ca2+,Ca2+i与AP和心肌收缩的关系,The mechanism for positive inotropic effect,The mechanism for positive inotropic effect,Cardiac glycosides,MLCK:Myosin light chain kinase肌球蛋白轻链激酶,SERCA:Sarco-endoplasmic Reticulum Calcium Atpase肌浆网钙泵,SOCE:store-operated calcium entry channels钙池操纵钙离子通道,RYR:Ryanodine receptor兰尼碱受体,强心苷 Na+-K+-ATPase Na+-K+交换Cell内Na+短暂 C内Na+超负荷，失K+影响Na+-Ca2+交换机制 Ca2+超负荷 异位节律点 自律性 Na+外流，Ca2+内流 迟后去极 Na+内流，Ca2+外流 C内 Ca2+i 心律失常 正性肌力,治疗量,中毒量,CICR,CICR:Calcium induced calcium release,说教法,HR,Mechanism：A：COactivating vagus nerve B：sensitivity of vagusSignificance：负性频率心动周期舒张期 心室充盈好 心肌自身供血 心肌获充分休息,心功能改善,Effects of cardiac glycosides on heart,2.Negative chronotropic action,窦房结自律性房室传导心房ERP浦肯野纤维自律性，ERP、传导,与增加迷走神经活性有关,3.Electrophysiological effects,抑制Na+-K+-ATP酶,增加迷走神经活性,Ca2+内流房室传导,房扑转为房颤,a.therapeutic dose,3.Electrophysiological effects,窦房结细胞KAch开放频率K+外流静息期膜电位（多负）自律性窦性频率,K+外流心房ERP缩短,促K+外流 心房肌静息电位加大 零相除极速度 心房传导速度,()Na+-K+-ATP酶K+i最大舒张电位（少负）接近阈电位自律性；,c.toxic dose,b.high dose（提高普氏纤维自律性）,Central sympathetic activity,Ca2+i；ERP（中毒时室速或室颤的机制）,K+外流ERP,最大舒张电位除极发生在较小的膜电位,与增加迷走神经活性有关,抑制Na+-K+-ATP酶,是强心苷引起室早、室性心律失常的原因之一,治疗房颤、房扑,使房扑转为房颤,3.Electrophysiological effects,With more toxic concentration,resting membrane potential is reduced as a result of inhibition of the sodium pump and reduced intracellular potassium.Glycosides toxicity:atrioventricular junctional rhythm,premature ventricular depolarization,bigeminal rhythm,and atrioventricular blockade.,3.Electrophysiological effects,Regulation of neuroendocrine activity,-Parasympathomimetic effectsAt lower dose:mainly affects atrial and atrioventricular nodal function.-Sympathomimetic effectsAt overdose,enhance the activity of sympathetic nervous centre.Anorexia厌食,nausea and vomiting,headache,fatigue,.-RAASrenin activity;Ag;aldosterone,1)Effects on vascular In normal individuals:peripheral vascular resistance(direct action)In patients with CHF:peripheral vascular resistance(indirect action)2)Effects on kidney A diuretic effect.cardiac function improvementinhibition of kidney tubular Na+-K+-ATPase,Extracardiac effects,Pharmacokinetics,Serum Principal Absorption Protein Therapeutic MetabolicDrugs(Per os)Binding T1/2 Concentration RouteDigoxin 6085%25%36h 0.52.0ng KidneyDigitoxin 90100%97%57d 1035ng/ml Liver,Therapeutic usesCHF,2.Arrhythmias:,1.心房纤颤：350-600次/分（f波）强心苷迷走兴奋房室传导 房室结隐匿性传导心室率 2.心房扑动：240-430次/分（F波）强心苷心房ERP扑动变颤动心室率；有些病人在停用强心苷后可恢复为窦性节律 3.阵发性室上性心动过速：迷走兴奋（现已少用),房扑,Drug actions and doses,1.Action vs Effect or Response2.Pharmacological effects and doses,Untoward effects,(1)Cardiac effects,(a)Premature ventricular beats and ventricular tachycardia and fibrillation(b)A-V block(c)Sinus bradycardia(60 bpm),Some factors evoking toxicity,HypokalemiaHypomagnesemiaHypercalcemiaMyocarditis心肌炎Myocardial anoxia缺氧Acid base imbalanceRenal insufficiency,Treatment of untoward effects,A.digoxin and potassium-depleting diuretics are discontinued.B.Potassium chloride;C.Phenytoin.D.Lidocaine.E.Atropine.F.Digoxin-specific antibody fragment(Fab):,(2)Anorexia,nausea and vomiting(often the earliest sign)(3)Headache,vision change,including abnormal color perception(often yellow or green vision).,1.明确中毒症状，停药指征;（心电图监测）2.血药浓度监测:地高辛3ng/ml,洋地黄毒苷45ng/ml-停药;3.注意药物相互作用：排钾利尿药：低血钾 加重毒性，注意补钾；钙阻滞剂、胺碘酮、普罗帕酮抑制地高辛经肾小管分泌减量；奎尼丁能自组织置换地高辛 肝药酶诱导剂 苯妥英钠-清除-血药浓度 拟肾上腺素药-心肌对强心苷敏感性,【中毒预防措施】,Non-Cardioglycoside Positive Inotropic Drugs,1.PDE inhibitors.cAMP Ca2+a positive inotropic effect vasodilation:direct action 1)Milrinone 米力农 2)Vesnarinone 维司力农 They have not been shown to reduce survival in placebo-controlled trials.,2.1-selective adrenoceptor agonist,Dobutamine多巴酚丁胺Ibopamine异布帕明Increase mortalityNot for regular use in CHF,Section VI Vasodilators,Effective in CHF because they provide a reduction in preload,or reduction in afterload,or both.Nitroprusside sodium:rapid afterload decrease,acute severe CHF.,3.Calcium channel blokers,AmlodipineFelodipine They are effective arterial vasodilators and reduce the afterload of heart.Reduce HR,facilitating diastolic relaxation and lowering diastolic filling pressures.Not for routine use in CHF.,PDEI,PDEI,利尿药,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NYHA心功能级：控制危险因素；ACEI。NYHA心功能级：ACEI；利尿剂；-R阻滞剂；地高辛用或不用。NYHA心功能级：ACEI；利尿剂；-R阻滞剂；地高辛。NYHA心功能级：ACEI；利尿剂；地高辛；醛固酮受体拮抗剂；病情稳定者，谨慎应用-R阻滞剂。,Thank you!,3,