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

ApoptosisExtracellular matrix(ECM)

fibrosisMyocardial hypertrophy and remodel

ing.

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 Ventri

cular Block , ventricular premature beat Therapy: K, phenytoin sodium, lidocaine. Antibody of i

t.

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. AngⅡ

( )

Hypertrophy & proliferation

of myocardium & VSMC

b. Afterload

Antagonist of AT1 (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.