digitalis lecture
DESCRIPTION
TRANSCRIPT
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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.
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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
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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
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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
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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
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• 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
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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
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%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
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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
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