Drugs Used In the Treatment ofDrugs Used In the Treatment ofCongestive Heart FailureCongestive Heart Failure

Garrett J. Gross, Ph.D.Garrett J. Gross, Ph.D.

Drugs Used In the Treatment ofDrugs Used In the Treatment ofCongestive Heart FailureCongestive Heart Failure

Garrett J. Gross, Ph.D.Garrett J. Gross, Ph.D.

Prototype drugs to know for treatment of heart failure

• Inotropes – digoxin, inamrinone,dobutamine, dopamine

• Diuretics - hydrochlorothiazide, furosemide, amiloride, spironolactone

• ACE inhibitors – captopril, enalapril,lisinopril

• AII receptor blockers-valsartan,losartan

• Sympatholytics – propranolol, carvedilol

• Vasodilators – glyceryl trinitrate, hydralazine, sodium nitroprusside

DEFINITIONDEFINITION

“The situation when the heart is

incapable of maintaining a cardiac

output adequate to accommodate

metabolic requirements and the

venous return."

“The situation when the heart is

incapable of maintaining a cardiac

output adequate to accommodate

metabolic requirements and the

venous return."E. BraunwaldE. Braunwald

EVOLUTION OF CLINICAL STAGES

EVOLUTION OF CLINICAL STAGES

NORMALNORMAL

Asymptomatic LV DysfunctionAsymptomatic LV Dysfunction

CompensatedCHF

CompensatedCHF

DecompensatedCHF

DecompensatedCHF

No symptomsNormal exerciseNormal LV fxn

No symptomsNormal exerciseNormal LV fxn

No symptomsNormal exerciseAbnormal LV fxn

No symptomsNormal exerciseAbnormal LV fxn

No symptoms ExerciseAbnormal LV fxn

No symptoms ExerciseAbnormal LV fxn

Symptoms ExerciseAbnormal LV fxn

Symptoms ExerciseAbnormal LV fxn

RefractoryCHF

RefractoryCHF

Symptoms not controlled with treatmentSymptoms not controlled with treatment

Chronic Congestive Heart FailureChronic Congestive Heart Failure

DIGOXIN NEUROHORMONAL EFFECTS

DIGOXIN NEUROHORMONAL EFFECTS

Plasma Noradrenaline

Peripheral nervous system activity

RAAS activity

Vagal tone

Normalizes arterial baroreceptors

Plasma Noradrenaline

Peripheral nervous system activity

RAAS activity

Vagal tone

Normalizes arterial baroreceptors

• Dig. Converts At.-Flutter At. Fibrillation (benefit)

• At. Flutter 300 (Atrial) 150 bpm (Vent.)

• At. Fib. 400 (Atrial) 100 bpm(Vent.)

• Dig. Vagal Tone to Atrial Muscle - Ach Acts on M Receptor to ERP in atrium

2:1

4:1

- Block A-V Node with Dig. Vent. Rate Further

Ach

DigitalisNormal

DIGOXIN TOXICITY

CARDIAC MANIFESTATIONSDIGOXIN TOXICITY

CARDIAC MANIFESTATIONS

ARRHYTHMIAS :- Ventricular (PVCs, VT, VF)- Supraventricular (PACs, SVT)

BLOCKS:- S-A and A-V blocks

CHF EXACERBATION

ARRHYTHMIAS :- Ventricular (PVCs, VT, VF)- Supraventricular (PACs, SVT)

BLOCKS:- S-A and A-V blocks

CHF EXACERBATION

%WORSENING

OF CHF

%WORSENING

OF CHFp = 0.001p = 0.001DIGOXIN: 0.125 - 0.5 mg /d

(0.7 - 2.0 ng/ml)EF < 35%Class I-III (digoxin+diuretic+ACEI)Also significantly decreased exercisetime and LVEF.

DIGOXIN: 0.125 - 0.5 mg /d (0.7 - 2.0 ng/ml)EF < 35%Class I-III (digoxin+diuretic+ACEI)Also significantly decreased exercisetime and LVEF.

DIGOXIN EFFECT ON CHF PROGRESSION

DIGOXIN EFFECT ON CHF PROGRESSION

RADIANCEN Engl J Med 1993;329:1RADIANCEN Engl J Med 1993;329:1

Placebo n=93DIGOXIN Withdrawal

Placebo n=93DIGOXIN Withdrawal

DIGOXIN n=85DIGOXIN n=85

3030

1010

00

2020

1001008080202000 4040 6060DaysDays

5050

4040

3030

2020

1010

00

Placebon=3403Placebon=3403

DIGOXINn=3397DIGOXINn=3397

484800 1212 2424 3636

OVERALL MORTALITY OVERALL MORTALITY

%%

DIGN Engl J Med 1997;336:525

DIGN Engl J Med 1997;336:525 MonthsMonths

p = 0.8p = 0.8