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1、Chapter 27Cardiac Glycosides&Other Drugs Used in Congestive Heart Failure南开大学医学院南开大学医学院张京玲张京玲 王侃王侃Chapter 27目的 掌握强心甙的作用，机制，毒性与临床应用。了解强心甙的来源，体内过程及用法。熟悉其他非强心苷类抗慢性心功能不全药物的作用特点。Chapter 27内容定义，来源，化构与作用的关系。强心苷强心苷的药理作用：1）正性肌力作用：选择性，直接加强心肌的收缩力，提高心肌最大缩短速度Vmax及每搏作功量。对心肌氧耗及输出量的影响。讨论正性肌力作用原理：使心肌细胞内钙离子量增加因而加强心肌收
2、缩力。Na+-K+-ATP酶的抑制与正性肌力作用及毒性作用的关系。Chapter 27内容2）负性频率作用：由正性肌力作用反射性兴奋迷走神经而减慢窦性频率，这种作用对治疗效果的关系。3）对心肌电生理特性的影响：对窦房结及浦氏纤维自律性的影响；对房室结，浦氏纤维及心房心室肌的传导性的影响。对房室结，浦氏纤维及心房心室肌的有效不应期的影响。4）对心电图的影响：T波，ST段，P-R及Q-T间期，P-P间期的变化。Chapter 27内容体内过程体内过程洋地黄毒甙，地高辛，毒毛旋花子甙的口服吸收率，生物可用度，排泄，半衰期的差别。毒性反应及防治毒性反应及防治，胃肠道，神经系统的不良反应，心脏毒性反应的
3、表现。各种异位节律的心律失常，传导阻滞与心动过缓。停药指症。苯妥英钠，钾盐等的应用。Chapter 27内容临床应用临床应用1）治疗各种慢性心功能不全有不同疗效。治疗房颤房扑的作用根据及效果。治疗室上性心动过速的应用。2）用法：全效量（洋地黄化）与维持量。全效量的速给发法与缓给法。地高辛小量蓄积法及其实用价值。其他非强心苷类抗慢性心功能不全药物的作用特点与临床应用。Drugs Used in Heart FailureI.IntroductionII.ClassificationIII.Positive inotropic drugsIV.Non-positive inotropic effe
4、ct drugs1.Cardiac glycosides2.Non-cardiac glycosidesDrugs Used in Heart FailureI.Introduction1.Chronic or congestive heart failure,CHF2.Pathophysiology of heart failureIntroduction3.Influence factorsContractility Heart ratePreloadAfterloadDrugs Used in Heart FailureII.Classification1.Positive inotro
5、pic drugs Cardiac Glycosides Other positive inotropic drugs used in heart failure2.Non-positive inotropic drugsDrugs Used in Heart FailureCardiac Glycosidesa.Chemistryb.Classificationc.Pharmacokineticsd.pharmacodynamicsCardiac Glycosidesa.ChemistryDrugs Used in Heart Failureb.ClassificationLong-acti
6、ng:digitoxinModerate-acting:digoxinShort-acting:strophanthin K,cedilanidec.PharmacokineticsNamedigitoxindigoxinCedilanid,strophenthin KNumber of-OH123Lipid solubilityhighmediumlowOral availability90-100%60-85%20-30%,2-5%Half-life(hours)1684023,12-19distributionWidely,easy pass placenta,in milk,Prote
7、in binding90%20-40%0metabolism80%20%Very littleUnchanged excretion10%60-90%90-100%Enterohepatic circulation27%7%Very littlefeaturesOrally,long,accumulationOrally,mediumiv.short,no accumulationDrugs Used in Heart Failured.PharmacodynamicsPharmacodynamic effectsMechanism of actionsClinical usesAdverse
8、 effectsDrugs Used in Heart FailurePharmacodynamic effectsCardiac effectsNervous systemVascular and renal effectsDrugs Used in Heart FailureCardiac effectsPositive inotropic actionfeaturesIncrease cardiac contractilityIncrease cardiac outputDecrease oxygen consumptionDrugs Used in Heart FailureHR co
9、ntractilityVentricularSizeOxygen consumptionCHFCardiac GlycosidesThe oxygen consumption before and after administrationDrugs Used in Heart FailureNegative chronotropic actionConductionLocalDoseComponents of nervesECGDrugs Used in Heart FailureNervous systemNA concentration in circulationInhibition o
10、f sympathetic activityInhibition of RASIn toxic doses,active CNSDrugs Used in Heart FailureVascular and renal effectsBlood vessels contraction-normal individualBlood vessels tone decrease-patientsDiuretic effectsDrugs Used in Heart FailureMechanism of actionsNa+/K+ATPase appears to be the primary ta
11、rget of cardiac glycosides.All cardiac glycosides inhibit the Na+/K+ATPase.Drugs Used in Heart FailureClinical usesTreatment of chronic congestive heart failureTreatment of some arrhythmiaatria fibrillationatria flutterparoxysmal supraventricular tachycardiaDrugs Used in Heart FailureAdverse effects
12、(toxicity)Gastrointestinal effectsanorexia,nausea,vomiting,and diarrhea.direct effects on GI tract,also the result of CNS actions,include CTZ stimulation.Drugs Used in Heart FailureNervous system effects vagal and chemoreceptor zone stimulation,disorientation and hallucinations-especially in the eld
13、erly-and visual disturbances(aberrations of color perception),agitation and even convulsions occasionally occur.Drugs Used in Heart FailureHeart effects the most severe effects,cause every variety of arrhythmia,including premature ventricular depolarizations,bigeminal rhythm,ventricular tachycardia
14、and fibrillation,atrioventricular blockade,sinus bradycardia,Drugs Used in Heart FailurePrevention and treatment of toxicityPreventionObserve the signs before toxicity occurs;Determine the blood concentration of the drugDecrease the factors causing toxicityDrugs Used in Heart FailureTreatment Tachyc
15、ardiaintravenous infusion or oral administration of potassium chloride,phenytoin sodium,lidocaine,Drugs Used in Heart FailureBradycardiaatropinedigitalis antibodies(digoxin immune fab),Stopping enterohepatic circulations,Drugs Used in Heart FailureOther positive inotropic drugs used in heart failure
16、a.Phosphodiesterases inhibitorsamrinone and milrinoneb.Selective 1-adrenoceptor stimulantsdobutamineDrugs Used in Heart FailureIV.Non-positive inotropic effect drugs1.Diuretics2.Angiotensin-converting enzyme inhibitors at present,considered as first-line therapy before digitalis.3.Vasodilators4.-adrenoceptor blockers谢谢观看/欢迎下载BY FAITH I MEAN A VISION OF GOOD ONE CHERISHES AND THE ENTHUSIASM THAT PUSHES ONE TO SEEK ITS FULFILLMENT REGARDLESS OF OBSTACLES.BY FAITH I BY FAITH