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 a. Ang Ⅱ ( ) Hypertrophy & proliferation of myocardium & VSMC b. Afterload Antagonist of AT 1 (Losartan) BK NO ( - ) diastolic dysfunction ( + )

OTHERS β-R blockers β-R sensitivity RAS DIURETICS CCB proliferation LOAD Vasodilatiors

REVIEW & QUESTIONS The mechanisms of cardiac glycosides. The ADR of them. The classification of drugs for CHF.