抗慢性心功能不全藥

抗慢性心功能不全藥Chapter27

CardiacGlycosides&OtherDrugsUsedinCongestiveHeartFailure張京玲王侃Chapter27目的掌握強心甙的作用，機制，毒性與臨床應用。了解強心甙的來源，體內(nèi)過程及用法。熟悉其他非強心苷類抗慢性心功能不全藥物的作用特點。Chapter27內(nèi)容定義，來源，化構與作用的關系。強心苷的藥理作用：1）正性肌力作用：選擇性，直接加強心肌的收縮力，提高"心肌最大縮短速度Vmax"及每搏作功量。對心肌氧耗及輸出量的影響。討論正性肌力作用原理：使心肌細胞內(nèi)鈣離子量增加因而加強心肌收縮力。Na+-K+-ATP酶的抑制與正性肌力作用及毒性作用的關系。Chapter27內(nèi)容2）負性頻率作用：由正性肌力作用反射性興奮迷走神經(jīng)而減慢竇性頻率，這種作用對治療效果的關系。3）對心肌電生理特性的影響：對竇房結(jié)及浦氏纖維自律性的影響；對房室結(jié)，浦氏纖維及心房心室肌的傳導性的影響。對房室結(jié)，浦氏纖維及心房心室肌的有效不應期的影響。4）對心電圖的影響：T波，ST段，P-R及Q-T間期，P-P間期的變化。Chapter27內(nèi)容體內(nèi)過程洋地黃毒甙，地高辛，毒毛旋花子甙的口服吸收率，生物可用度，排泄，半衰期的差別。毒性反應及防治，胃腸道，神經(jīng)系統(tǒng)的不良反應，心臟毒性反應的表現(xiàn)。各種異位節(jié)律的心律失常，傳導阻滯與心動過緩。停藥指癥。苯妥英鈉，鉀鹽等的應用。Chapter27內(nèi)容臨床應用1）治療各種慢性心功能不全有不同療效。治療房顫房撲的作用根據(jù)及效果。治療室上性心動過速的應用。2）用法：全效量（洋地黃化）與維持量。全效量的速給發(fā)法與緩給法。地高辛小量蓄積法及其實用價值。其他非強心苷類抗慢性心功能不全藥物的作用特點與臨床應用。DrugsUsedinHeartFailureIntroductionClassificationPositiveinotropicdrugsNon-positiveinotropiceffectdrugsCardiacglycosidesNon-cardiacglycosidesDrugsUsedinHeartFailureIntroductionChronicorcongestiveheartfailure,CHFPathophysiologyofheartfailureIntroductionInfluencefactorsContractilityHeartratePreloadAfterloadDrugsUsedinHeartFailureClassificationPositiveinotropicdrugsCardiacGlycosidesOtherpositiveinotropicdrugsusedinheartfailureNon-positiveinotropicdrugsDrugsUsedinHeartFailureCardiacGlycosidesChemistryClassificationPharmacokineticspharmacodynamicsCardiacGlycosidesChemistryDrugsUsedinHeartFailureClassificationLong-acting:digitoxinModerate-acting:digoxinShort-acting:strophanthinK,cedilanidePharmacokineticsNamedigitoxindigoxinCedilanid,strophenthinKNumberof-OH12>3LipidsolubilityhighmediumlowOralavailability90-100%60-85%20-30%,2-5%Half-life(hours)1684023,12-19distributionWidely,easypassplacenta,inmilk,Proteinbinding>90%20-40%0metabolism>80%<20%VerylittleUnchangedexcretion10%60-90%90-100%Enterohepaticcirculation27%7%VerylittlefeaturesOrally,long,accumulationOrally,mediumiv.short,noaccumulationDrugsUsedinHeartFailurePharmacodynamicsPharmacodynamiceffectsMechanismofactionsClinicalusesAdverseeffectsDrugsUsedinHeartFailurePharmacodynamiceffectsCardiaceffectsNervoussystemVascularandrenaleffectsDrugsUsedinHeartFailureCardiaceffectsPositiveinotropicactionfeaturesIncreasecardiaccontractilityIncreasecardiacoutputDecreaseoxygenconsumptionDrugsUsedinHeartFailureHRcontractilityVentricularSizeOxygenconsumptionCHF↑↓↑↑↑CardiacGlycosides↓↑↓↓↓TheoxygenconsumptionbeforeandafteradministrationDrugsUsedinHeartFailureNegativechronotropicactionConductionLocalDoseComponentsofnervesECGDrugsUsedinHeartFailureNervoussystem↓NAconcentrationincirculationInhibitionofsympatheticactivityInhibitionofRASIntoxicdoses,activeCNSDrugsUsedinHeartFailureVascularandrenaleffectsBloodvesselscontraction----normalindividualBloodvesselstonedecrease----patientsDiureticeffectsDrugsUsedinHeartFailureMechanismofactionsNa+/K+ATPaseappearstobetheprimarytargetofcardiacglycosides.AllcardiacglycosidesinhibittheNa+/K+ATPase.DrugsUsedinHeartFailureClinicalusesTreatmentofchroniccongestiveheartfailureTreatmentofsomearrhythmiaatriafibrillationatriaflutterparoxysmalsupraventriculartachycardiaDrugsUsedinHeartFailureAdverseeffects(toxicity)Gastrointestinaleffectsanorexia,nausea,vomiting,anddiarrhea.directeffectsonGItract,alsotheresultofCNSactions,includeCTZstimulation.DrugsUsedinHeartFailureNervoussystemeffectsvagalandchemoreceptorzonestimulation,disorientationandhallucinations----especiallyintheelderly----andvisualdisturbances(aberrationsofcolorperception),agitationandevenconvulsionsoccasionallyoccur.DrugsUsedinHeartFailureHearteffectsthemostsevereeffects,causeeveryvarietyofarrhythmia,includingprematureventriculardepolarizations,bigeminalrhythm,ventriculartachycardiaandfibrillation,atrioventricularblockade,sinusbradycardia,DrugsUsedinHeartFailurePreventionandtreatmentoftoxicityPreventionObservethesignsbeforetoxicityoccurs;DeterminethebloodconcentrationofthedrugDecreasethefactorscausingtoxicityDrugsUsedinHeartFailureTreatmentTachycardiaintravenousinfusionororaladministrationofpotassiumchloride,phenytoinsodium,lidocaine,DrugsUsedinHeartFailureBradycardiaatropinedigitalisantibodies(digoxinimmunefab),Stoppingenterohepaticcirculations,DrugsUsedinHeartFailureOtherpositiveinotropicdrugsusedinheartfailurePhosphodiesterasesinhibitorsamrinoneandmilrinoneSelectiveβ1-adr