没有标题浙江大学教学信息化平台.pptx

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1、Contents OverviewOverview ACE inhibitors ACE inhibitors Diuretics Diuretics receptor blockers receptor blockers Cardiac glycoside Cardiac glycoside Others OthersHeart(cardiac)failure is said to have occurred when the heart Heart(cardiac)failure is said to have occurred when the heart is no longer ab

2、le to maintain the circulation to the tissues for is no longer able to maintain the circulation to the tissues for normal metabolism.normal metabolism.第1页/共48页1.1.Pathophysiological changes of Pathophysiological changes of congestive heart failure(CHF)congestive heart failure(CHF)(1)Function and str

3、ucture changes(1)Function and structure changes(2)Increased sympathetic activity and(2)Increased sympathetic activity and down-regulation of down-regulation of receptor receptor(3)Activated renin-angiotensin-(3)Activated renin-angiotensin-aldosterone system(RAAS)aldosterone system(RAAS)A.A.OverviewO

4、verview第2页/共48页第3页/共48页Pathophysiological Pathophysiological changes of CHFchanges of CHF第4页/共48页Pathophysiological changes of CHFPathophysiological changes of CHF第5页/共48页Cardiac failureCardiac failureCardiac outputCardiac outputVenous pressureVenous pressureVenous hyperemiaVenous hyperemiaPulmonary

5、 Pulmonary circulation:circulation:cough,emptysis,cough,emptysis,dyspneadyspneaSystemic circulationSystemic circulation hyperemiahyperemia :jugular vein distension,jugular vein distension,edemaedemaBlood supplyBlood supplyRenal blood flowRenal blood flowRenin-angiotension Renin-angiotension Aldoster

6、one Aldosterone Sodium and waterSodium and waterretentionretentionChanges in hemodynamics of CHFChanges in hemodynamics of CHF第6页/共48页A.Overview2.Grades of CHF (A):(A):no symptoms no symptoms (B):(B):physical activities were limited and physical activities were limited and symptoms could be induced

7、by general symptoms could be induced by general activityactivity (C):(C):physical activities were markedly physical activities were markedly limited limited (D):(D):symptoms appear even at rest symptoms appear even at rest第7页/共48页3.3.Therapeutic strategies in CHF Therapeutic strategies in CHF(1)Incr

8、easing contractility of the(1)Increasing contractility of the cardiac musclescardiac muscles(2)Inhibiting RAAS(2)Inhibiting RAAS(3)Reducing sympathetic activity(3)Reducing sympathetic activity(4)Dilating vessels(4)Dilating vessels(5)Diuresis (5)Diuresis A.A.OverviewOverview CardiacCardiacremodelingr

9、emodeling DecreaseDecreaseoverloadoverload 第8页/共48页Drug therapy for CHFDrug therapy for CHF第9页/共48页ACEI:ACEI:captopril captopril 卡托普利卡托普利卡托普利卡托普利 enalapril enalapril 依那普利依那普利依那普利依那普利ATAT1 1 receptor antagonists:receptor antagonists:losartan losartan 氯沙坦氯沙坦氯沙坦氯沙坦 irbesartan irbesartan 伊白沙坦伊白沙坦伊白沙坦伊白沙

10、坦B.Angiotensin converting enzyme inhibitors(ACEI)and angiotensin receptor antagonists第10页/共48页Cardiovascular remodelingCardiovascular remodelingvasodilatationvasodilatationSystemic and localSystemic and local第11页/共48页ACEI1.1.Pharmacological effectsPharmacological effectsInhibiting the production of

11、Ang IIInhibiting the production of Ang II vasoconstriction vasoconstriction ;sodium;sodium retention retention ;cardiac remodeling(myocardial cardiac remodeling(myocardial hypertrophy)hypertrophy)Inhibiting the degradation of Inhibiting the degradation of bradykinin bradykinin vasodilatation vasodil

12、atation Increasing ANP and scavenging free Increasing ANP and scavenging free radicalsradicals B.Angiotensin converting enzyme inhibitors(ACEI)and angiotensin receptor antagonists第12页/共48页Box Actions of angiotensin II through activating AT1 receptorsConstricting vessels,increase peripheral Constrict

13、ing vessels,increase peripheral resistance and returned blood volume.resistance and returned blood volume.Increasing sympathetic tension,promote Increasing sympathetic tension,promote release of sympathetic transmitter.release of sympathetic transmitter.Stimulating release of aldosteroneStimulating

14、release of aldosterone.Rapidly inducing expression of Rapidly inducing expression of c-fos,c-c-fos,c-jun,Egr-1,c-myc,etc.jun,Egr-1,c-myc,etc.第13页/共48页Cardiovascular effectsCardiovascular effects Decrease resistance of peripheral vessels Decrease resistance of peripheral vessels Dilate coronary arter

15、y,increase blood supply of heart and kidney,Dilate coronary artery,increase blood supply of heart and kidney,improve cardiac and renal functionimprove cardiac and renal function Reverse myocardial hypertrophy and ventricular remodeling Reverse myocardial hypertrophy and ventricular remodeling B.Angi

16、otensin converting enzyme inhibitors(ACEI)and angiotensin receptor antagonists第14页/共48页B.Angiotensin converting enzyme inhibitors(ACEI)and angiotensin receptor antagonists2.Clinical uses(1)CHF(1)CHF increase motor increase motor tolerancetolerance decrease mortality decrease mortality(2)Hypertension

17、(2)Hypertension 第15页/共48页3.Adverse effects HypotensionHypotensionCough and angioedemaCough and angioedemaHyperpotassemiaHyperpotassemia Rashes and altered tastesRashes and altered tastesContraindications:Contraindications:pregnancy and pregnancy and stenosis of renal artery stenosis of renal artery

18、B.Angiotensin converting enzyme inhibitors(ACEI)and angiotensin receptor antagonists第16页/共48页AT1 receptor antagonistsCompared with ACEI:Compared with ACEI:Blocking actions of angiotensin Blocking actions of angiotensin II directlyII directlyNot affecting bradykinin Not affecting bradykinin metabolis

19、mmetabolismProtecting renal functionProtecting renal functionUsed for CHF and hypertensionUsed for CHF and hypertension B.Angiotensin converting enzyme inhibitors(ACEI)and angiotensin receptor antagonists第17页/共48页1.1.Pharmacological effectsPharmacological effects Reduce blood volume by increasing Na

20、Reduce blood volume by increasing Na+and and water excretionwater excretion Reduce NaReduce Na+-Ca-Ca2+2+exchange in vascular smooth exchange in vascular smooth muscle cellsmuscle cells2.2.Clinical uses Clinical uses CHF:CHF:grand I IV(mainly used in II III),grand I IV(mainly used in II III),alone o

21、r combined with other drugs alone or combined with other drugs Edema,hypertension,Edema,hypertension,etc.etc.3.Adverse effects3.Adverse effects imbalance of electrolytes/acid-base;imbalance of electrolytes/acid-base;plasma level of renin plasma level of renin ;hypokalemia;hypokalemia;hyperuricemia;h

22、yperglycemia/hyperlipidemiahyperuricemia;hyperglycemia/hyperlipidemiaC.C.DiureticsDiuretics第18页/共48页Therapeutic effects of Therapeutic effects of diuretics in CHFdiuretics in CHF第19页/共48页Main Main diureticsdiureticsThiazideThiazides sLoop Loop diureticdiuretics sK+K+sparing sparing diureticsdiuretic

23、s第20页/共48页类类 别别(主要作用部位主要作用部位)其他分类名其他分类名作用机制作用机制利尿应用利尿应用非利尿应用非利尿应用碳酸酐酶抑制药碳酸酐酶抑制药碳酸酐酶抑制药碳酸酐酶抑制药（近曲小管）（近曲小管）（近曲小管）（近曲小管）/抑制碳酸酐酶抑制碳酸酐酶抑制碳酸酐酶抑制碳酸酐酶利尿药耐受的病利尿药耐受的病利尿药耐受的病利尿药耐受的病人人人人,与袢利尿药合与袢利尿药合与袢利尿药合与袢利尿药合用用用用青光眼，高山病，青光眼，高山病，青光眼，高山病，青光眼，高山病，代谢性碱中毒代谢性碱中毒代谢性碱中毒代谢性碱中毒渗透性利尿药渗透性利尿药渗透性利尿药渗透性利尿药（髓袢及其他部（髓袢及其他部（髓袢

24、及其他部（髓袢及其他部位）位）位）位）脱水药脱水药脱水药脱水药增高尿液渗透压增高尿液渗透压增高尿液渗透压增高尿液渗透压急性肾功能衰竭急性肾功能衰竭急性肾功能衰竭急性肾功能衰竭脑水肿，青光眼脑水肿，青光眼脑水肿，青光眼脑水肿，青光眼袢利尿药（髓袢袢利尿药（髓袢袢利尿药（髓袢袢利尿药（髓袢升支粗段）升支粗段）升支粗段）升支粗段）1.1.高效能利尿药高效能利尿药高效能利尿药高效能利尿药2.Na2.Na+-K-K+-2C1-2C1同同同同向转运体抑制药向转运体抑制药向转运体抑制药向转运体抑制药抑制抑制抑制抑制NaNa+-K-K+-2C1-2C1同向转运同向转运同向转运同向转运各种严重水肿，各种严重水肿

25、，各种严重水肿，各种严重水肿，急性肾功能衰竭急性肾功能衰竭急性肾功能衰竭急性肾功能衰竭高钙血症，加速高钙血症，加速高钙血症，加速高钙血症，加速毒物排出毒物排出毒物排出毒物排出噻嗪类利尿药噻嗪类利尿药噻嗪类利尿药噻嗪类利尿药（远曲小管）（远曲小管）（远曲小管）（远曲小管）1.1.中效能利尿药中效能利尿药中效能利尿药中效能利尿药2.Na2.Na+-C1-C1同向转同向转同向转同向转运体抑制药运体抑制药运体抑制药运体抑制药抑制抑制抑制抑制NaNa+-C1-C1同向同向同向同向转运转运转运转运各种水肿各种水肿各种水肿各种水肿高血压，高尿钙高血压，高尿钙高血压，高尿钙高血压，高尿钙症，尿崩症症，尿崩症症

26、，尿崩症症，尿崩症保钾利尿药（集保钾利尿药（集保钾利尿药（集保钾利尿药（集合管、末段远曲合管、末段远曲合管、末段远曲合管、末段远曲小管）小管）小管）小管）低效能利尿药低效能利尿药低效能利尿药低效能利尿药1.1.拮抗醛固酮作拮抗醛固酮作拮抗醛固酮作拮抗醛固酮作用（螺内酯）用（螺内酯）用（螺内酯）用（螺内酯）2.2.抑制上皮细胞抑制上皮细胞抑制上皮细胞抑制上皮细胞NaNa+通道（氨苯蝶通道（氨苯蝶通道（氨苯蝶通道（氨苯蝶啶，阿米洛利）啶，阿米洛利）啶，阿米洛利）啶，阿米洛利）水肿（尤其对伴水肿（尤其对伴水肿（尤其对伴水肿（尤其对伴有醛固酮增高者，有醛固酮增高者，有醛固酮增高者，有醛固酮增高者，如肝

27、硬化病人）如肝硬化病人）如肝硬化病人）如肝硬化病人）失钾和失钾和失钾和失钾和/或失镁或失镁或失镁或失镁第21页/共48页Commonly used:Commonly used:carvedilol carvedilol 卡维地洛卡维地洛卡维地洛卡维地洛,bisoprolol,bisoprolol 比索比索比索比索洛尔洛尔洛尔洛尔,sustained-release metoprolol ,sustained-release metoprolol 缓释型缓释型缓释型缓释型美托洛尔美托洛尔美托洛尔美托洛尔 1.1.Pharmacological effectsPharmacological eff

28、ects(1)Blocking effects of catecholamines on(1)Blocking effects of catecholamines on myocardium:myocardium:decreasing heart rate and decreasing heart rate and cardiac oxygen demandcardiac oxygen demand(2)Up-regulating(2)Up-regulating receptor receptor(3)Inhibiting RAAS and VP(vosopressin,(3)Inhibiti

29、ng RAAS and VP(vosopressin,加压素加压素加压素加压素):):anti-myocardial hypertrophy and remodeling anti-myocardial hypertrophy and remodeling(4)Reducing cardiac oxygen remand,(4)Reducing cardiac oxygen remand,vasodilatation vasodilatation(receptor receptor block)block)(5)Anti-arrhythmic and anti-hypertensive(5)A

30、nti-arrhythmic and anti-hypertensive effectseffects D.D.receptor receptor blockersblockers第22页/共48页2.2.Clinical usesClinical uses(1)CHF:(1)CHF:grand II-III grand II-III decreasing mortality decreasing mortality(2)Other uses:(2)Other uses:hypertension,arrhythmias,hypertension,arrhythmias,angina,angin

31、a,etcetc.D.D.receptor receptor blockersblockers第23页/共48页Therapeutic effects of Therapeutic effects of receptor antagonists receptor antagonists on cardiac function in CHF patientson cardiac function in CHF patientsD.receptor blockers第24页/共48页3.3.Adverse effects Adverse effects Inhibition of cardiac

32、functionInhibition of cardiac function Contraindications:Contraindications:severe heart failure severe heart failure severe A-V block severe A-V block hypotension hypotension worsening bronchial worsening bronchial asthmaasthmaD.receptor blockers第25页/共48页E.E.Cardiac glycosideCardiac glycoside(digita

33、lis)(digitalis)Cardiac glycoside:It is a kind of glycoside compounds which can selectively act on cardiac muscle,and increase the force of myocardial contraction.第26页/共48页Digoxin 地高辛地高辛地高辛地高辛E.Cardiac glycoside(digitalis)第27页/共48页1.1.Pharmacological effectsPharmacological effects(1)Positive inotropi

34、c effects(1)Positive inotropic effects inhibiting Nainhibiting Na+-K-K+-ATPase-ATPase free Ca free Ca2+2+excitation-contraction coupling excitation-contraction coupling cardiac output cardiac output organ blood supply organ blood supply Vmax Vmax diastolic duration diastolic duration venous venous r

35、eturn return coronary coronary blood supply blood supply cardiac oxygen consumption cardiac oxygen consumption E.Cardiac glycoside(digitalis)第28页/共48页Inhibition of NaInhibition of Na+-K-K+-ATPase by digitalis and-ATPase by digitalis and potentiation of cardiac muscle contractionpotentiation of cardi

36、ac muscle contraction第29页/共48页第30页/共48页第31页/共48页(2)Negative chronotropic effects Reflex inhibition of sympathetic activity cardiac output cardiac output Sympathetic activity Sympathetic activity HR HR Increasing vagal activity directly Reducing AV conduction:Reducing AV conduction:ventricular rate v

37、entricular rate E.Cardiac glycoside(digitalis)第32页/共48页(3)Electrophysiological effects decreasing automaticity of sinoatrial nodedecreasing automaticity of sinoatrial node slow conduction,slow conduction,especially AV conductionespecially AV conduction increasing automaticity of increasing automatic

38、ity of PurkinjePurkinje fibres fibres shortening ERP of fast response cells shortening ERP of fast response cellsMechanisms:Mechanisms:intracellular Na intracellular Na+,K,K+,Ca Ca2+2+MDP MDP ,afterdepolarization,afterdepolarization E.Cardiac glycoside(digitalis)第33页/共48页Overdose:Overdose:NaNa+,K,K+

39、,Ca,Ca2+2+MDP MDP afterdepolarization afterdepolarizationElectrophysiological basis for digitalis Electrophysiological basis for digitalis overdoseoverdose第34页/共48页ECG:ECG:P-R P-R ;S-T/T wave S-T/T wave ;various arrhythmias;various arrhythmiasP-R P-R S-T/T wave S-T/T wave prematural ventricular beat

40、prematural ventricular beat第35页/共48页(4)Other effectsVessels:Vessels:vasoconstriction vasoconstriction Central nervous system:Central nervous system:CTZ dopamine D CTZ dopamine D2 2 receptor receptor mental and vision disorders mental and vision disordersKidneyKidney increase blood supply of kidney i

41、ncrease blood supply of kidney diuretic effect:decrease Na diuretic effect:decrease Na+reabsorption reabsorption E.Cardiac glycoside(digitalis)第36页/共48页2.Clinical uses(1)Congestive heart failure(CHF)(1)Congestive heart failure(CHF)especially associated with atrial fibrillation especially associated

42、with atrial fibrillation and sinus tachycardiaand sinus tachycardia(2)Arrhythmias(2)Arrhythmias atrial fibrillation/atrial flutter:atrial fibrillation/atrial flutter:paroxysmal surpraventricular tachycardiaparoxysmal surpraventricular tachycardia E.Cardiac glycoside(digitalis)第37页/共48页3.Adverse effe

43、cts(1)Gastrointestinal effects(1)Gastrointestinal effects nausea,vomiting,nausea,vomiting,etc.etc.(2)CNS effects(2)CNS effects alteration of color perceptionalteration of color perception（色视色视色视色视,such assuch as yellow yellow vision vision 黄视黄视黄视黄视）;headache,fatigue,confusion,;headache,fatigue,confu

44、sion,etc.etc.E.Cardiac glycoside(digitalis)第38页/共48页(3)Cardiac toxicity(3)Cardiac toxicity arrhythmiasarrhythmias：prematural beats,prematural beats,tachycardiatachycardia，atrioventricular block,sinus atrioventricular block,sinus bradycardia,bradycardia,etc.etc.PreventionPrevention：Dose individualiza

45、tionDose individualization Avoiding provocation factors:plasma K Avoiding provocation factors:plasma K+,and drug,and drug interactions,interactions,etc.etc.TreatmentTreatment：KCl,phenytoin or lidocaine,KCl,phenytoin or lidocaine,i.v.i.v.Atropine:Atropine:A-V block,sinus bradycardia A-V block,sinus b

46、radycardia Fab segment of digoxin antibody,Fab segment of digoxin antibody,i.v.i.v.E.Cardiac glycoside(digitalis)第39页/共48页Drug Drug interactions that interactions that probably induce probably induce digitalis digitalis cardiotoxicitycardiotoxicity第40页/共48页4.Administration(1)Loading+maintaining dose

47、sfull dose(digitalization)+maintaining full dose(digitalization)+maintaining dosesdosesfor severe patientsfor severe patients(2)Maintaining dose given daily reaching steady state of plasma reaching steady state of plasma concentration with 1 week(digoxin)concentration with 1 week(digoxin)for stable

48、patients for stable patientsE.Cardiac glycoside(digitalis)第41页/共48页5.ADME and properties of different digitalis drugs(1)Moderate-acting:digoxin digoxin 地高辛地高辛地高辛地高辛(2)Long-acting：digitoxin digitoxin 洋地黄毒苷洋地黄毒苷洋地黄毒苷洋地黄毒苷 digitalization+maintaining dosesdigitalization+maintaining doses(3)Short-acting：

49、deslanoside deslanoside 西地兰西地兰西地兰西地兰,去乙酰毛花苷去乙酰毛花苷去乙酰毛花苷去乙酰毛花苷 acute attack of CHFacute attack of CHFE.Cardiac glycoside(digitalis)第42页/共48页第43页/共48页1.1.receptor agonists receptor agonists dobutamine dobutamine 多巴酚丁胺多巴酚丁胺多巴酚丁胺多巴酚丁胺 Positive inotropic drugsPositive inotropic drugs Arrhythmias,Arrhythm

50、ias,etc.etc.2.2.PDE-III inhibitors PDE-III inhibitors milrinone milrinone 米力农米力农米力农米力农,vesnarinone,vesnarinone 维司力农维司力农维司力农维司力农，amrinoneamrinone 安力农安力农安力农安力农 Positive inotropic drugsPositive inotropic drugs Hypotension,Hypotension,thrombocytopeniathrombocytopenia,etc.etc.F.Other drugs 第44页/共48页3.3.V