抗慢性心功能不全药

Chapter27CardiacGlycosides&OtherDrugsUsedinCongestiveHeartFailure南开大学医学院张京玲王侃Chapter27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。Chapter27内容•定义，来源，化构与作用的关系。•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缩力。Na+-K+-ATP酶的抑制与正性肌力作用及毒性作用的关系。Chapter27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。Chapter27内容•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，胃肠道，神经系统的不良反应，心脏毒性反应的表现。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。Chapter27内容•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。DrugsUsedinHeartFailureI.IntroductionII.ClassificationIII.PositiveinotropicdrugsIV.Non-positiveinotropiceffectdrugs1.Cardiacglycosides2.Non-cardiacglycosidesDrugsUsedinHeartFailureI.Introduction1.Chronicorcongestiveheartfailure,CHF2.PathophysiologyofheartfailureIntroduction3.Influencefactors①Contractility②Heartrate③Preload④AfterloadDrugsUsedinHeartFailureII.Classification1.PositiveinotropicdrugsCardiacGlycosidesOtherpositiveinotropicdrugsusedinheartfailure2.Non-positiveinotropicdrugsDrugsUsedinHeartFailure①CardiacGlycosidesa.Chemistryb.Classificationc.Pharmacokineticsd.pharmacodynamicsCardiacGlycosidesa.ChemistryDrugsUsedinHeartFailureb.ClassificationLong-acting:digitoxinModerate-acting:digoxinShort-acting:strophanthinK,cedilanidec.PharmacokineticsNamedigitoxindigoxinCedilanid,strophenthinKNumberof-OH123LipidsolubilityhighmediumlowOralavailability90-100%60-85%20-30%,2-5%Half-life(hours)1684023,12-19distributionWidely,easypassplacenta,inmilk,Proteinbinding90%20-40%0metabolism80%20%VerylittleUnchangedexcretion10%60-90%90-100%Enterohepaticcirculation27%7%VerylittlefeaturesOrally,long,accumulationOrally,mediumiv.short,noaccumulationDrugsUsedinHeartFailured.PharmacodynamicsPharmacodynamiceffectsMechanismofactionsClinicalusesAdverseeffectsDrugsUsedinHeartFailurePharmacodynamiceffects•Cardiaceffects•Nervoussystem•VascularandrenaleffectsDrugsUsedinHeartFailure•CardiaceffectsPositiveinotropicactionfeaturesIncreasecardiaccontractilityIncreasecardiacoutputDecreaseoxygenconsumptionDrugsUsedinHeartFailureHRcontractilityVentricularSizeOxygenconsumptionCHF↑↓↑↑↑CardiacGlycosides↓↑↓↓↓TheoxygenconsumptionbeforeandafteradministrationDrugsUsedinHeartFailureNegativechronotropicactionConductionLocalDoseComponentsofnervesECGDrugsUsedinHeartFailure•Nervoussystem↓NAconcentrationincirculationInhibitionofsympatheticactivityInhibitionofRASIntoxicdoses,activeCNSDrugsUsedinHeartFailure•VascularandrenaleffectsBloodvesselscontraction----normalindividualBloodvesselstonedecrease----patientsDiureticeffectsDrugsUsedinHeartFailureMechanismofactionsNa+/K+ATPaseappearstobetheprimarytargetofcardiacglycosides.AllcardiacglycosidesinhibittheNa+/K+ATPase.DrugsUsedinHeartFailureClinicaluses•Treatmentofchroniccongestiveheartfailure•TreatmentofsomearrhythmiaatriafibrillationatriaflutterparoxysmalsupraventriculartachycardiaDrugsUsedinHeartFailureAdverseeffects(toxicity)•Gastrointestinaleffectsanorexia,nausea,vomiting,anddiarrhea.directeffectsonGItract,alsotheresultofCNSactions,includeCTZstimulation.DrugsUsedinHeartFailure•Nervoussystemeffectsvagalandchemoreceptorzonestimulation,disorientationandhallucinations----especiallyintheelderly----andvisualdisturbances(aberrationsofcolorperception),agitationandevenconvulsionsoccasionallyoccur.DrugsUsedinHeartFailure•Hearteffectsthemostsevereeffects,causeeveryvarietyofarrhythmia,includingprematureventriculardepolarizations,bigeminalrhythm,ventriculartachycardiaandfibrillation,atrioventricularblockade,sinusbradycardia,DrugsUsedinHeartFailurePreventionandtreatmentoftoxicity•PreventionObservethesignsbeforetoxicityoccurs;DeterminethebloodconcentrationofthedrugDecreasethefactorscausingtoxicityDrugsUsedinHeartFailure•TreatmentTachycardiaintravenousinfusionororaladministrationofpotassiumchloride,phenytoinsodium,lidocaine,DrugsUsedinHeartFailureBradycardiaatropinedigitalisantibodies(digoxinimmunefab),Stoppingenterohepaticcirculations,DrugsUsedinHeartFailure②Otherpositiveinotropicdrugsusedinheartfailurea.Phosphodiesterasesinhibitorsamrinoneandmilrinoneb.Selectiveβ1-adrenoceptorstimulantsdobutamineDrugsUsedinHeartFailureIV.Non-positiveinotropiceffectdrugs1.Diuretics2.Angiotensin-convertingenzymeinhibitorsatpresent,consideredasfirst-linetherapybeforedigitalis.3.Vasodilators4.β-adrenoceptorblockers