没有标题浙江大学教学信息化平台PPT学习教案.pptx

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1、会计学1没有没有(mi yu)标题浙江大学教学信息化平台标题浙江大学教学信息化平台第一页，共48页。Contentsn n Overviewn n ACE inhibitorsn n Diureticsn n receptor blockersn n Cardiac glycosiden n OthersHeart(cardiac)failure is said to have occurred when the heart is no longer Heart(cardiac)failure is said to have occurred when the heart is no long

2、er able to maintain the circulation to the tissues for normal metabolism.able to maintain the circulation to the tissues for normal metabolism.第1页/共48页第二页，共48页。1.1.Pathophysiological changes of congestive heart failure Pathophysiological changes of congestive heart failure(CHF)(CHF)(1)Function and s

3、tructure 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-aldosterone system(3)Activated renin-angiotensin-aldosterone system(RAAS)(RAAS)A.Overview第

4、2页/共48页第三页，共48页。第3页/共48页第四页，共48页。Pathophysiological changes of CHFPathophysiological changes of CHF第4页/共48页第五页，共48页。Pathophysiological changes of CHFPathophysiological changes of CHF第5页/共48页第六页，共48页。Cardiac failureCardiac failureCardiac outputCardiac outputVenous pressureVenous pressureVenous hypere

5、miaVenous hyperemiaPulmonary circulation:Pulmonary circulation:cough,emptysis,dyspneacough,emptysis,dyspneaSystemic circulationSystemic circulation hyperemiahyperemia :jugular vein distension,edemajugular vein distension,edemaBlood supplyBlood supplyRenal blood flowRenal blood flowRenin-angiotension

6、 Renin-angiotension Aldosterone Aldosterone Sodium and waterSodium and waterretentionretentionChanges in hemodynamics of CHFChanges in hemodynamics of CHF第6页/共48页第七页，共48页。A.Overview2.2.Grades of CHFGrades of CHF (A):(A):no symptoms no symptoms (B):(B):physical activities were limited and physical ac

7、tivities were limited and symptoms could be induced 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页第八页，共48页。3.Therape

8、utic strategies in CHF(1)Increasing contractility of the cardiac muscles(1)Increasing contractility of the cardiac 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.Overview Cardi

9、acCardiacremodelingremodeling DecreaseDecreaseoverloadoverload 第8页/共48页第九页，共48页。Drug therapy for CHFDrug therapy for CHF第9页/共48页第十页，共48页。ACEI:captopril 卡卡托普利托普利 enalapril 依那依那普利普利AT1 receptor antagonists:losartan 氯沙氯沙坦坦 irbesartan 伊伊白沙白沙(bi sh)坦坦B.Angiotensin converting enzyme inhibitors(ACEI)and an

10、giotensin receptor antagonists第10页/共48页第十一页，共48页。Cardiovascular remodelingCardiovascular remodelingvasodilatationvasodilatationSystemic and localSystemic and local第11页/共48页第十二页，共48页。ACEI1.Pharmacological effectsn nInhibiting the production of Ang IIInhibiting the production of Ang IIn n vasoconstric

11、tion vasoconstriction ;sodium retention;sodium retention ;n n cardiac remodeling(myocardial hypertrophy)cardiac remodeling(myocardial hypertrophy)n nInhibiting the degradation of bradykinin Inhibiting the degradation of bradykinin n n vasodilatation vasodilatation n nIncreasing ANP and scavenging fr

12、ee radicalsIncreasing ANP and scavenging free radicals B.B.Angiotensin converting enzyme inhibitors Angiotensin converting enzyme inhibitors(ACEI)and angiotensin receptor antagonists(ACEI)and angiotensin receptor antagonists第12页/共48页第十三页，共48页。Box Actions of angiotensin II through activating AT1 rece

13、ptors Constricting vessels,increase peripheral Constricting 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 tr

14、ansmitter.Stimulating release of aldosteroneStimulating release of aldosterone.Rapidly inducing expression of Rapidly inducing expression of c-fos,c-jun,c-fos,c-jun,Egr-1,c-myc,etc.Egr-1,c-myc,etc.第13页/共48页第十四页，共48页。Cardiovascular effectsCardiovascular effects Decrease resistance of peripheral vesse

15、ls Decrease resistance of peripheral vessels Dilate coronary artery,increase blood supply of heart and kidney,improve cardiac and renal function Dilate coronary artery,increase blood supply of heart and kidney,improve cardiac and renal function Reverse myocardial hypertrophy and ventricular remodeli

16、ng Reverse myocardial hypertrophy and ventricular remodeling B.B.Angiotensin converting enzyme Angiotensin converting enzyme inhibitors(ACEI)and angiotensin receptor inhibitors(ACEI)and angiotensin receptor antagonistsantagonists第14页/共48页第十五页，共48页。B.B.Angiotensin converting enzyme Angiotensin conver

17、ting enzyme inhibitors(ACEI)and angiotensin inhibitors(ACEI)and angiotensin receptor antagonistsreceptor antagonists2.2.Clinical usesClinical uses(1)CHF(1)CHF increase motor increase motor tolerancetolerance decrease mortality decrease mortality(2)Hypertension(2)Hypertension 第15页/共48页第十六页，共48页。3.Adv

18、erse effects HypotensionHypotensionn nCough and angioedemaCough and angioedeman nHyperpotassemiaHyperpotassemia n nRashes and altered tastesRashes and altered tastesn nContraindications:Contraindications:pregnancy and stenosis of renal pregnancy and stenosis of renal artery artery B.B.Angiotensin co

19、nverting enzyme Angiotensin converting enzyme inhibitors(ACEI)and angiotensin receptor inhibitors(ACEI)and angiotensin receptor antagonistsantagonists第16页/共48页第十七页，共48页。AT1 receptor antagonistsCompared with ACEI:n nBlocking actions of angiotensin II directlyBlocking actions of angiotensin II directl

20、yn nNot affecting bradykinin metabolismNot affecting bradykinin metabolismn nProtecting renal functionProtecting renal functionn nUsed for CHF and hypertensionUsed for CHF and hypertension B.B.Angiotensin converting enzyme Angiotensin converting enzyme inhibitors(ACEI)and angiotensin inhibitors(ACEI

21、)and angiotensin receptor antagonistsreceptor antagonists第17页/共48页第十八页，共48页。1.1.Pharmacological effectsPharmacological effects n nReduce blood volume by increasing NaReduce blood volume by increasing Na+and water excretion and water excretionn nReduce NaReduce Na+-Ca-Ca2+2+exchange in vascular smoot

22、h muscle cells exchange in vascular smooth muscle cells2.2.Clinical uses Clinical usesn nCHF:CHF:grand I IV(mainly used in II III),grand I IV(mainly used in II III),alone or combined alone or combined with other drugs with other drugs n nEdema,hypertension,Edema,hypertension,etc.etc.3.Adverse effect

23、s3.Adverse effects imbalance of electrolytes/acid-base;imbalance of electrolytes/acid-base;plasma level of renin plasma level of renin ;hypokalemia;hypokalemia;hyperuricemia;hyperglycemia/hyperlipidemiahyperuricemia;hyperglycemia/hyperlipidemiaC.Diuretics第18页/共48页第十九页，共48页。Therapeutic effects of The

24、rapeutic effects of diuretics in CHFdiuretics in CHF第19页/共48页第二十页，共48页。Main Main diureticsdiureticsThiazidesThiazidesLoop Loop diureticsdiureticsK+K+sparing sparing diureticsdiuretics第20页/共48页第二十一页，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

25、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

26、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，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

27、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，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

28、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页第二十二页，共48页。Commonly used:carvedilol 卡维地卡维地洛洛,bi

29、soprolol 比索比索(b su)洛尔洛尔,sustained-release metoprolol 缓缓释型美托洛尔释型美托洛尔 1.Pharmacological effects(1)Blocking effects of catecholamines on myocardium:decreasing heart rate and cardiac oxygen demand(2)Up-regulating receptor(3)Inhibiting RAAS and VP(vosopressin,加压素加压素):anti-myocardial hypertrophy and remod

30、eling(4)Reducing cardiac oxygen remand,vasodilatation(receptor block)(5)Anti-arrhythmic and anti-hypertensive effects D.receptor blockers第22页/共48页第二十三页，共48页。2.Clinical uses(1)CHF:(1)CHF:grand II-III grand II-III decreasing mortality decreasing mortality(2)Other uses:(2)Other uses:hypertension,arrhyt

31、hmias,angina,hypertension,arrhythmias,angina,etcetc.D.receptor blockers第23页/共48页第二十四页，共48页。Therapeutic effects of Therapeutic effects of receptor antagonists on receptor antagonists on cardiac function in CHF patientscardiac function in CHF patientsD.receptor blockers第24页/共48页第二十五页，共48页。3.Adverse ef

32、fectsn nInhibition of cardiac functionn nContraindications:n n severe heart failure severe heart failure severe A-V block severe A-V block hypotension hypotension worsening bronchial asthma worsening bronchial asthmaD.receptor blockers第25页/共48页第二十六页，共48页。E.Cardiac glycoside(digitalis)Cardiac glycosi

33、deCardiac glycoside:It is a kind of:It is a kind of glycoside compounds which can glycoside compounds which can selectively act on cardiac selectively act on cardiac muscle,and increase the force of muscle,and increase the force of myocardial contraction.myocardial contraction.第26页/共48页第二十七页，共48页。Di

34、goxin 地高辛地高辛地高辛地高辛E.Cardiac glycoside(digitalis)第27页/共48页第二十八页，共48页。1.1.Pharmacological effectsPharmacological effects(1)Positive inotropic effects(1)Positive inotropic effects inhibiting Nainhibiting Na+-K-K+-ATPase-ATPase free Ca free Ca2+2+excitation-excitation-contraction coupling contraction co

35、upling cardiac output cardiac output organ blood supply organ blood supply Vmax Vmax diastolic duration diastolic duration venous return venous return coronary blood supply coronary blood supply cardiac oxygen consumption cardiac oxygen consumption E.Cardiac glycoside(digitalis)第28页/共48页第二十九页，共48页。I

36、nhibition of NaInhibition of Na+-K-K+-ATPase by digitalis and-ATPase by digitalis and potentiation of cardiac muscle contractionpotentiation of cardiac muscle contraction第29页/共48页第三十页，共48页。第30页/共48页第三十一页，共48页。第31页/共48页第三十二页，共48页。(2)Negative chronotropic effects(2)Negative chronotropic effects Reflex

37、 inhibition of sympathetic Reflex inhibition of sympathetic activityactivity cardiac output cardiac output Sympathetic activity Sympathetic activity HR HR Increasing vagal activityIncreasing vagal activity directlydirectly Reducing AV conduction:Reducing AV conduction:ventricular rate ventricular ra

38、te E.Cardiac glycoside(digitalis)第32页/共48页第三十三页，共48页。(3)Electrophysiological effects (3)Electrophysiological effects decreasing automaticity of sinoatrial nodedecreasing automaticity of sinoatrial node slow conduction,slow conduction,especially AV conductionespecially AV conduction increasing automa

39、ticity of increasing automaticity 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4

40、8页第三十四页，共48页。Overdose:Overdose:NaNa+,K,K+,Ca,Ca2+2+MDP MDP afterdepolarization afterdepolarizationElectrophysiological basis for digitalis overdoseElectrophysiological basis for digitalis overdose第34页/共48页第三十五页，共48页。ECG:ECG:P-R P-R ;S-T/T wave S-T/T wave ;various arrhythmias;various arrhythmiasP-R P

41、-R S-T/T wave S-T/T wave prematural ventricular beatprematural ventricular beat第35页/共48页第三十六页，共48页。(4)Other effects(4)Other effectsVessels:Vessels:vasoconstriction vasoconstriction Central nervous system:Central nervous system:CTZ dopamine D CTZ dopamine D22 receptor receptor mental and vision disor

42、ders mental and vision disordersKidneyKidney increase blood supply of kidney increase blood supply of kidney diuretic effect:decrease Na diuretic effect:decrease Na+reabsorption reabsorption E.Cardiac glycoside(digitalis)第36页/共48页第三十七页，共48页。2.2.Clinical usesClinical uses(1)Congestive heart failure(C

43、HF)(1)Congestive heart failure(CHF)especially associated with atrial fibrillation and especially associated with atrial fibrillation and sinus tachycardiasinus tachycardia(2)Arrhythmias(2)Arrhythmias atrial fibrillation/atrial flutter:atrial fibrillation/atrial flutter:paroxysmal surpraventricular t

44、achycardiaparoxysmal surpraventricular tachycardia E.Cardiac glycoside(digitalis)第37页/共48页第三十八页，共48页。3.3.Adverse effectsAdverse effects(1)Gastrointestinal effects(1)Gastrointestinal effects nausea,vomiting,nausea,vomiting,etc.etc.(2)CNS effects(2)CNS effects alteration of color perceptionalteration

45、of color perception（色视色视色视色视,such assuch as yellow vision yellow vision 黄视黄视黄视黄视）;headache,fatigue,confusion,headache,fatigue,confusion,etc.etc.E.Cardiac glycoside(digitalis)第38页/共48页第三十九页，共48页。(3)Cardiac toxicity(3)Cardiac toxicity arrhythmiasarrhythmias：prematural beats,prematural beats,tachycardi

46、atachycardia，atrioventricular block,sinus bradycardia,atrioventricular block,sinus bradycardia,etc.etc.PreventionPrevention：Dose individualizationDose individualization Avoiding provocation factors:plasma K Avoiding provocation factors:plasma K+,and drug interactions,and drug interactions,etc.etc.Tr

47、eatmentTreatment：KCl,phenytoin or lidocaine,KCl,phenytoin or lidocaine,i.v.i.v.Atropine:Atropine:A-V block,sinus bradycardia A-V block,sinus bradycardia Fab segment of digoxin antibody,Fab segment of digoxin antibody,i.v.i.v.E.Cardiac glycoside(digitalis)第39页/共48页第四十页，共48页。Drug interactions Drug int

48、eractions that probably that probably induce digitalis induce digitalis cardiotoxicitycardiotoxicity第40页/共48页第四十一页，共48页。4.4.AdministrationAdministration(1)Loading+maintaining doses(1)Loading+maintaining doses full dose(digitalization)+maintaining dosesfull dose(digitalization)+maintaining doses for

49、severe patientsfor severe patients(2)Maintaining dose given daily(2)Maintaining dose given daily reaching steady state of plasma concentration reaching steady state of plasma concentration with 1 week(digoxin)with 1 week(digoxin)for stable patients for stable patientsE.Cardiac glycoside(digitalis)第4

50、1页/共48页第四十二页，共48页。5.5.ADME and properties of different digitalis ADME and properties of different digitalis drugsdrugs(1)Moderate-acting:(1)Moderate-acting:digoxin digoxin 地高辛地高辛地高辛地高辛(2)Long-acting(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