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Drugs for Congestive Heart Failure BACKGROUND DEFINITION: The inability of heart to meet the needs of peripheral systems. PATHOGENY: myocardium contraction & heart load SYMPTOMS: weakness, fatigue and dyspnea, cyanosis, edema . Change of myocardial structure in CHF Apoptosis Extracellular matrix(ECM) fibrosis Myocardial hypertrophy and remodeling. Change of myocardial function in CHF Systolic dysfunction actin-troponin-tropomyosin system ATP Ca-excitation-contraction-coupling Diastolic dysfunction compliance Change of neural-endocrine system in CHF sympathetic nerve system activation renin-angiotensin-aldosterone system activation Arginine-Vasopressin Endothelin Tumor necrosis factor- α Atrial natriuretic peptide EDRF-NO Prostaglandins Classification of Drugs for CHF Cardiac glycosides ACEI Diuretics Others β-R blockers CCB PDEI(phosphodiestrase inhibitor) Vasodilators Cardiac Glycosides Positive inotropic effect K-Na-ATPase Na Ca Ca Effects on neural-hormone To inhibit sympathetic nerve activity To enhance vagus nerve activity Electrophysiologic effects Effects on ECG Effects on Kidney Cardiac Glycosides P.K Absorption Distribution Metabolism Excretion Influencing factors Cardiac Glycosides Clinic uses CHF Arrhythmia: Atrial fibrillation, Atrial flutter ADR Extracardiac Cardiac: Supra -/-Ventricular arrhythmia , Atrial Ventricular Block , ventricular premature beat Therapy: K, phenytoin sodium, lidocaine. Antibody of it. Cardiac Glycosides Interactions: Antiarrhythmia Agents Digitoxin, Cediland, Strophanthin K PDEI (milrinone, amrinone, vesnarinone) ATP AC cAMP PDEI 5’AMP Ca influx RAS BLOCKERS ACEI (Captopril, enalapril) Mechanism BK a. AngⅡ ( ) (-) NO Hypertrophy & proliferation of myocardium & VSMC b. Afterload diastolic dysfunction ( + ) Antagonist of AT1 (Losartan) OTHERS β-R blockers β-R sensitivity RAS DIURETICS CCB proliferation Vasodilatiors LOAD REVIEW & QUESTIONS The mechanisms of cardiac glycosides. The ADR of them. The classification of drugs for CHF.