抗慢性心功能不全药

1、抗慢性心功能不全药目的 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。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缩力。Na+-K+-ATP酶的抑制与正性肌力作用及毒性作用的关系。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

2、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。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。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

3、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。I.IntroductionII. ClassificationIII. Positive inotropic drugsIV. Non-positive inotropic effect drugs1.Cardiac glycosides2.Non-cardiac glycosidesI.Introduction1. Chronic or congestive heart failure, CHF2. Pathophysiology of heart failure3. Influence fa

4、ctorsContractility Heart ratePreloadAfterloadII.Classification1. Positive inotropic drugs Cardiac Glycosides Other positive inotropic drugs used in heart failure2. Non-positive inotropic drugs Cardiac Glycosidesa. Chemistryb. Classificationc. Pharmacokineticsd. pharmacodynamicsCardiac Glycosidesa. C

5、hemistryb. Classification Long-acting: digitoxin Moderate-acting: digoxin Short-acting: strophanthin K, cedilanidec. PharmacokineticsNamedigitoxindigoxinCedilanid, strophenthin KNumber of -OH123Lipid solubilityhighmediumlowOral availability90-100%60-85%20-30%, 2-5%Half-life (hours)1684023, 12-19dist

6、ributionWidely, easy pass placenta, in milk,Protein binding90%20-40%0metabolism80%20%Very littleUnchanged excretion10%60-90%90-100%Enterohepatic circulation27%7%Very littlefeaturesOrally, long, accumulationOrally, mediumiv. short, no accumulationd. Pharmacodynamics Pharmacodynamic effects Mechanism

7、of actions Clinical uses Adverse effectsPharmacodynamic effects Cardiac effects Nervous system Vascular and renal effects Cardiac effectsPositive inotropic actionfeaturesIncrease cardiac contractilityIncrease cardiac outputDecrease oxygen consumptionHR contractilityVentricularSizeOxygen consumptionC

8、HFCardiac GlycosidesThe oxygen consumption before and after administrationNegative chronotropic actionConductionLocalDoseComponents of nervesECG Nervous systemNA concentration in circulationInhibition of sympathetic activityInhibition of RASIn toxic doses, active CNS Vascular and renal effectsBlood

9、vessels contraction-normal individualBlood vessels tone decrease-patientsDiuretic effectsMechanism of actionsNa+/K+ ATPase appears to be the primary target of cardiac glycosides. All cardiac glycosides inhibit the Na+/K+ ATPase.Clinical uses Treatment of chronic congestive heart failure Treatment of

10、 some arrhythmiaatria fibrillationatria flutterparoxysmal supraventricular tachycardiaAdverse effects (toxicity) Gastrointestinal effectsanorexia, nausea, vomiting, and diarrhea.direct effects on GI tract, also the result of CNS actions, include CTZ stimulation. Nervous system effects vagal and chem

11、oreceptor zone stimulation, disorientation and hallucinations-especially in the elderly -and visual disturbances (aberrations of color perception), agitation and even convulsions occasionally occur. Heart effects the most severe effects, cause every variety of arrhythmia, including premature ventric

12、ular depolarizations, bigeminal rhythm, ventricular tachycardia and fibrillation, atrioventricular blockade, sinus bradycardia, Prevention and treatment of toxicity PreventionObserve the signs before toxicity occurs;Determine the blood concentration of the drugDecrease the factors causing toxicity T

13、reatment Tachycardiaintravenous infusion or oral administration of potassium chloride, phenytoin sodium, lidocaine,Bradycardiaatropinedigitalis antibodies (digoxin immune fab),Stopping enterohepatic circulations, Other positive inotropic drugs used in heart failurea. Phosphodiesterases inhibitorsamrinone and milrinoneb. Selective 1-adrenoceptor stimula