《【教学课件】第二十四章抗慢性心功能不全药.ppt》由会员分享，可在线阅读，更多相关《【教学课件】第二十四章抗慢性心功能不全药.ppt（61页珍藏版）》请在taowenge.com淘文阁网|工程机械CAD图纸|机械工程制图|CAD装配图下载|SolidWorks_CaTia_CAD_UG_PROE_设计图分享下载上搜索。
1、Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Chapter 24抗慢性心功能不全药Drugs Used in the Treatment of congestive heart failure“CHF”Guangdong University of TechnologyGuangdong University of Technology轻工化工学院objective掌握强心苷的一般药理，地高辛卡托普利用于CHF作用特点。熟悉利尿药、氨氯地平、米力农及其他非苷类抗CHF的作用及特点、扩血管药的
2、应用根据及选药。了解CHF的病理生理及其他药物的抗CHF作用特点。Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Guangdong University of TechnologyGuangdong University of Technology轻工化工学院心脏的泵血功能1.心肌收缩的特点“全或无”收缩相邻心肌细胞具有润盘的特殊结构，出生于心室某
3、一处的兴奋，通过润盘迅速传递，引起组成心室的所有心肌细胞几乎同步收缩。不发生完全强直收缩与骨骼肌不同，当刺激频率较高时，后一次刺激引起的骨骼肌收缩可发生在前一次刺激所引起的基础上，发生完全强直收缩。心肌细胞的有效不应期（ERP）特别长，相当于整个心肌细胞的收缩期和舒张早期。自动节律性心肌细胞分为工作细胞和特殊分化细胞，特殊分化细胞分布在窦房结、房室交界、希氏束、浦肯野纤维等，构成特殊的传导系统；特殊分化细胞都具有自动产生节律性兴奋的能力。Guangdong University of TechnologyGuangdong University of Technology轻工化工学院心脏的泵血
4、功能心脏泵血机制心动周期心脏一次收缩和舒张构成一个机械性活动周期，称为心动周期。在一个心动周期内，心房和心室均可以产生收缩和舒张活动，心室肌的收缩和舒张造成室内压力的变化，是导致心房和心室之间以及心室和主动脉之间产生压力梯度的主要原因，而心房的收缩和舒张生产是影响较少。压力梯度是推动血液在相应腔室之间流动的主要动力。室内压力的变化和血液的单方向流动，需要在瓣膜活动的配合下实现。Guangdong University of TechnologyGuangdong University of Technology轻工化工学院心脏的泵血功能影响心排出量的因素每分钟内一侧心室排血的总量，也称每分排出
5、量，CO取决于心率和每搏排出量。前负荷：心室舒张期所承受的压力，用心室舒张期末期容量表示。后负荷：指动脉血压心肌收缩力：收缩蛋白、调节蛋白、物质代谢、能量供应、细胞内钙离子浓度、ATP酶的活性等心率：神经因素（交感神经、迷走神经）、体液因素（循环血液中的肾上腺素、去甲肾上腺素、甲状腺素）、体温等。Guangdong University of TechnologyGuangdong University of Technology轻工化工学院1introductionWhatsCHF?Congestiveheartfailure（CHF）isaclinicalsyndromeofcardiac
6、dysfunction（心功能不全）.Itsalsocalled“overloadedmyocardiopathy”(超负荷心肌病）Guangdong University of TechnologyGuangdong University of Technology轻工化工学院1introductionSymptomsassociatedwithcongestiveheartfailureAcuteChronictachycardia心动过速Variousarrhythmias心律失常Shortnessofbreath短促呼吸hypertension高血压Edema(peripheral/p
7、ulmonary)cardiomegaly心肥大Decreasedexercisetolerance运动耐量Edema(peripheral外周/pulmonary与肺有关)Guangdong University of TechnologyGuangdong University of Technology轻工化工学院1introductionleft ventricle功能障碍功能障碍 运动耐力运动耐力arhythmia 心律失常心律失常congestive heart failure心衰心衰sudden death猝死猝死pathologyfeatureGuangdong Univers
8、ity of TechnologyGuangdong University of Technology轻工化工学院1introductionprognosis预后1、CHF mortality 死亡率死亡率3 year 30%5 year50%1 year50-70%(severe)2、death reason50%pump failure50%arrhythmiaGuangdong University of TechnologyGuangdong University of Technology轻工化工学院心功能不全心功能不全（心缩力（心缩力）CO 代偿机制代偿机制交感交感NS活性活性激活
9、激活RAAS 血管收缩血管收缩 水、钠潴留水、钠潴留心前、后负荷心前、后负荷耗氧耗氧久久失代偿失代偿循环衰竭循环衰竭A 灌注不足灌注不足V 淤血淤血正性肌力药正性肌力药心脏负荷药心脏负荷药（扩血管药、利尿药等）（扩血管药、利尿药等）ACEI其他其他Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Guangdong University of TechnologyGuangdong University of Technology轻工化工学院pathophysiologyFunction alte
10、ration 1)cardiac contractility 2)heart rate 3)heart loadStructure alteration 1)myocardial cell apoptosis（凋亡）凋亡）2)extracellular matrix（细胞外基质）细胞外基质）3）remodeling（重构）重构）Guangdong University of TechnologyGuangdong University of Technology轻工化工学院ComparisonofnormalandabnormalheartCardiac contractility（心收缩心收
11、缩力）力）CO，LVEDP左心室舒张末期压左心室舒张末期压Myocardial hypertrophy(心肌肥厚）心肌肥厚）and remodeling（重构）重构）Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Classificationofdrugs1、Positive inotropic agents（正性肌力药）正性肌力药）cardiacglycoside强心苷digoxin，digitoxin；non-cardiacglycosidemilrinone米力农，ibopamine异波帕
12、胺；Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Classificationofdrugs2、RAAS1)ACEI:captopril卡托普利,enalapril依那普利2)AT1antagonists血管紧张素受体阻滞药:losartan氯沙坦,valsartan缬沙坦3)Aldosterone醛固酮antagonist:spironolacton安体舒通Guangdong University of TechnologyGuangdong University of Technology
13、轻工化工学院Classificationofdrugs3、Reduce load agents(降低负荷药降低负荷药）vasodilators:nitroglycerin硝酸甘油，血管扩张剂 diuretics:DCT，furosemide；4、Others -R blocker：carvedilol卡维地洛卡维地洛;Ca2+antagonists：amlodipine氨氯地平氨氯地平Guangdong University of TechnologyGuangdong University of Technology轻工化工学院usualdrugs强心苷强心苷cardiac glycosid
14、es【definition】selective act on the heart myocardial contractility（心肌收缩力）心肌收缩力）;used for CHF&supraventricular arrhythmias（室上性心律失常）（室上性心律失常）.include：digitoxin，digoxin，cedilanide（毛花苷），strophanthin K（毒毛花苷）；Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Cardiacglycosides chemic
15、al structure of digoxin内酯环内酯环甾核甾核糖糖苷苷元元苷苷Guangdong University of TechnologyGuangdong University of Technology轻工化工学院pharmacokineticsofCGs1、po.bioavailabilityisvariation;digoxinF60%80%(20%80%)；2、distributewidely;3、classificationofCGsaccordingtotheireliminationmode:longeffectdigitoxin洋地黄毒苷moderateeffec
16、tdigoxin地高辛shorteffectcedilanide（毛花苷），strophanthinK（毒毛花苷）Guangdong University of TechnologyGuangdong University of Technology轻工化工学院pharmacological actions1.positive inotropic action （正性肌力作用）Selectivity is higher(选择性高选择性高)；the myocardial contractility Guangdong University of TechnologyGuangdong Unive
17、rsity of Technology轻工化工学院characteristics:1 cardiacmusclecontractpromptly，diastoleprolongreversely（舒张期相对延长）；themaximaltension（最高张力）;themaximalshortingvelocity（最大缩短速率）;Guangdong University of TechnologyGuangdong University of Technology轻工化工学院characteristics:2 COinpatientwithCHF;3 myocardialoxygenconsu
18、mptioninpatientwithCHF（衰竭心脏的耗氧量）How reduce myocardial oxygen consumption of CHF？Guangdong University of TechnologyGuangdong University of Technology轻工化工学院contractility H RVentricular wall tensionCHFoxygen consumptionCGs心室张力心室张力Guangdong University of TechnologyGuangdong University of Technology轻工化工学
19、院mechanismofaction Na+-K+-ATPase Na+-K+exchange intracellular Na+Na+-Ca2+exchange intracellularCa2+the force of cardiac contractionNKANCE3Na+2K+digoxin Na+Ca2+Ca2+Na+Guangdong University of TechnologyGuangdong University of Technology轻工化工学院pharmacological actions2、negative chronotropic action （负性频率作
20、用）（负性频率作用）1)indirect actionmyocardial contractilityvagalactivity（迷走迷走N N活性活性）reflex;HR；2)vagal sensitivity（迷走迷走N N敏感性敏感性）directly.Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Guangdong University of TechnologyGuangdong University of Technology轻工化工学院pharmacological action
21、s4、ECG T low or reverse，S-T fishhook type；P-R interphase；P-P interphase ；Q-T interphase .5、diuretic effect;renin activityGuangdong University of TechnologyGuangdong University of Technology轻工化工学院Clinicaluses1.CHFbesteffect:CHFaccompaniedbyatrialfibrillation（房颤）.bettereffect:hypertension,coronaryathe
22、roscleroticcardiopathy（冠脉粥样硬化性心脏病）.Guangdong University of TechnologyGuangdong University of Technology轻工化工学院noeffect：CHFinducedbypulmonaryheartdisease（肺心病）,activemyocarditis（活动性心肌炎）,seriouspericarditis（心包炎）.Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Clinicaluses2.Some
23、arrhythmias1）Atrialfibrillation（房颤）atrialrate400600time/minventricularrate100200time/minCO;digoxineffectsontheA-Vnodeconcealedconduction（隐匿性传导）ventricularrate（心室率）Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Clinicaluses2.Somearrhythmias2）Atrialflutter（房扑）atrialrate32036
24、0time/minventricularrate;digoxinERPofatria，AtrialflutterAtrialfibrillation，digoxindepressA-VconductionventricularrateGuangdong University of TechnologyGuangdong University of Technology轻工化工学院Adversereactions1.Gastrointestinal anorexia(厌食，厌食，the earliest sign of toxicity),nausea and vomiting2.CNS hea
25、dache,fatigue（疲劳）疲劳）,dizzy（眩晕眩晕）,delirium（谵妄谵妄）,visual（视觉视觉）changes3.Cardiac toxicity(the worst)Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Adversereactions3.Cardiac toxicity(the worst)Cardiac toxication:(introcellular K+)Premature ventricular beats（室早）33%AV-block 房室阻滞
26、18%AV node tachycardia 17%AV jointing rhythmia 12%Atrial tachycardia+AV block 10%Ventricular tachycardia（室性过速）8%Sinous arrest（窦性停搏）2%Guangdong University of TechnologyGuangdong University of Technology轻工化工学院treatmentofuntowardeffects1、prevention of toxic symptoms 1）avoid the factors altered the sens
27、itivity to cardiac glycoside(increase)：serum K+,Mg2+;serum Ca2+;Lower pH value;Myocardial ischemia（心肌缺血）;Drug influence Guangdong University of TechnologyGuangdong University of Technology轻工化工学院treatmentofuntowardeffects2)Observe the indications for withdrawal the drug（停药指征停药指征）:Sinus bradycardia（窦性
28、心动过缓窦性心动过缓）HR 60 beats/min.Ventricular tachycardia Abnormal color perception （色视异常色视异常）Guangdong University of TechnologyGuangdong University of Technology轻工化工学院treatmentofuntowardeffects3）measuration of serum concentration：digoxin 3ng/ml is toxic level（中毒水平）；2、Cessation of using the drugs（停药停药）supp
29、ly KCl po.or iv gtt.severe A-V block is not given!noticeGuangdong University of TechnologyGuangdong University of Technology轻工化工学院treatmentofuntowardeffects3、using antiarrhythmic drugs phenytoin sodium，lidocaine used to treat ventricular arrhythmia室性心律失常室性心律失常；atropine used to control bradycardia心动过
30、缓心动过缓、A-V block.4、using digoxin-Ab Fab segment Specificity is higher.Guangdong University of TechnologyGuangdong University of Technology轻工化工学院administration1、new method：Daily maintenance dose(每日维持量)：digoxin:0.25mg.d-1 after 67d （45 t1/2）Css(steady-state)1）toxicity occur；2）used in chronic CHF;3）not
31、be given to acute CHF or drugs with t1/2 over long；Guangdong University of TechnologyGuangdong University of Technology轻工化工学院administration2、old method：1）Total effective dose（全效量全效量）also called：loading dose（负荷量负荷量）,digitalizing dose（洋地黄化量洋地黄化量）2）Maintenance dose was used after total effective dose.G
32、uangdong University of TechnologyGuangdong University of Technology轻工化工学院Usualdrugs-RAASinhibitorsII、RAAS inhibitors肾素一血管紧张素一醛固酮系统II-1、血管紧张素血管紧张素I I转化酶抑制药转化酶抑制药 （Angiotensin-converting enzyme inhibitors ACEI）captopril fosinopril enalapril cilazapril ramiprilGuangdong University of TechnologyGuangdon
33、g University of Technology轻工化工学院1、inhibit ACE activityAngIAngIIBlood vessel（+）Aldosterone醛固酮醛固酮 Myocardial hypertrophy,remodelingBp ACE（kininase II）BKlose alive NO,PGI2 synthesis blood vessel dilationACEIreverseGuangdong University of TechnologyGuangdong University of Technology轻工化工学院ACEI2、inhibit m
34、yocardial hypertrophy and remodeling ventricular remodeline(心室重构心室重构)In CHF，myocardial hypertrophy with changes of left ventricular structure,cardiac efficiency（效能效能）Guangdong University of TechnologyGuangdong University of Technology轻工化工学院mechanismofreversionmyocardiaoverloadAng II activateCell gro
35、wth、proliferate ventricle hypertrophy and remodelingACEIGuangdong University of TechnologyGuangdong University of Technology轻工化工学院Guangdong University of TechnologyGuangdong University of Technology轻工化工学院ACEI【clinical uses】only one drug to prolong the survival of CHF patients.ACEI is used in combina
36、tion with diuretics、digoxin.They are basic drugs to treat CHF.Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Guangdong University of TechnologyGuangdong University of Technology轻工化工学院aldosterone antagonist spironolacton(螺内酯）螺内酯）competitive block aldosterone-R：Cell growth、p
37、roliferate;ventricle and vessels remodeling;alone used-weaker,used with ACEI-effects,mortalityGuangdong University of TechnologyGuangdong University of Technology轻工化工学院利尿药 diuretics thiazides（噻嗪类噻嗪类），DCT furosemide（呋塞米呋塞米）,spironolactone【actions and uses】excretionofNa+、H2O extracellular fluid volume
38、;vasodilations;Guangdong University of TechnologyGuangdong University of Technology轻工化工学院利尿药 diureticsSelection of diureticsmild CHF:DCT po；middle CHF ：po DCT+furosemide serious CHF：iv furosemide or+spironolactone;recommend:diuretics+digoxin+ACEI,-R drugs Guangdong University of TechnologyGuangdong
39、University of Technology轻工化工学院Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Guangdong University of TechnologyGuangdong Univ
40、ersity of Technology轻工化工学院1、vein dilation preload 硝酸甘油硝酸甘油 nitroglycerin 硝酸异山梨酯硝酸异山梨酯 isosorbide dinitrate2、arteriole dilation afterload 肼屈嗪肼屈嗪 hydralazine Guangdong University of TechnologyGuangdong University of Technology轻工化工学院3、venous and arteriole dilation preload、afterloadrapidly 硝普钠硝普钠 sodium
41、 nitroprusside4、1-R blocker A、V dilation 哌唑嗪哌唑嗪 prazosin Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Calcium channel blockers氨氯地平氨氯地平 amlodipine slow and prolonged,used in left ventricular dysfunction with angina（心绞痛）or hypertension for long time.Guangdong University of
42、 TechnologyGuangdong University of Technology轻工化工学院non-glycoside inotropic drugsdopamine iv.gtt acute CHF;dobutamine（多巴酚丁胺多巴酚丁胺）ibopamine （异布帕明）（异布帕明）Guangdong University of TechnologyGuangdong University of Technology轻工化工学院Guangdong University of TechnologyGuangdong University of Technology轻工化工学院questionsPlease describe the classes of drugs used to treat CHF.For each of these list examples,(especially CGs,ACEI)their mechanisms of action,indications and major adverse effects.