Pathophysiology of Congestive Heart Failure
Pathophysiology of Congestive Heart Failure
Pathophysiology of Congestive Heart Failure
Activate Renin-Angiotensin
Aldosterone system
ACEIs
ARB
Aldosterone
AT-II
Salt & Water
Retention.
Volume expansion
Vasoconstriction
Venous
Vasoconstriction
Increased Preload
Diuretics
Arterial
Vasoconstriction
Increased Preload
Venodilators
Increased Afterload
Arterial vasodilators
Parenteral drugs:
1. Diuretics: - Loop diuretics.
2. Vasodilators: - Sodium nitroprusside.
3. Sympathomimetics: - Dobutamine, Dopamine.
4. Phosphodiesterase inhibitors: - Inamrinone, Amrinone.
1)
2)
3)
ACEIs in C.H.F
Natriuresis
filling pressures
Organic Nitrates
Hydralazine
Ca++
Ca++ Na+
Na+ K+
Ca++
Ca++ Na+
Na+ K+
Ca++ stores in
Sarcoplasmic
Reticulum
1) Digitalis inhibits
Na+/K+ ATPase
4) Excitation-contraction
of Myofibrils
ii) Decreased preload (venous pressure) leading to decreased heart size and
improvement of cardiac performance and relief of pulmonary congestion.
iii) Decreased afterload increasing tissue perfusion.
iv) Decreased salt and water retention relieving edema.
II- Electrophysiological effects:
A- At Therapeutic doses: - Digitalis increases vagal tone and decreases sympathetic
activity resulting in:
1- Decreased heart rate.
2- Decreased conduction in AV node.
3- Decreased refractory period in atrial and ventricular tissues.
B- At Higher doses:
1- Increases automaticity by direct effect and sympathetic activation.
2- Decreases intracellular K+.
v These effects predispose to arrhythmia.
C- At Toxic doses: - Overloading of intracellular Ca++ leads to extra-systoles
leading to pulsus bigeminy then trigeminy and produces ventricular tachycardia
resulting in ventricular fibrillation.
v The simultaneous increase in automaticity and blockade of AV node conduction
and Ca++ overload produces All forms of arrhythmias.
Pharmacokinetics of Digoxin:
Moderately lipophilic, well absorbed from GIT.
Bioavailability 70%, plasma protein binding is 30%.
Widely distributed in all tissues including CNS and crosses placenta.
t1/2 is 36-48 hours.
Excreted unchanged by kidneys: Renal impairment prolongs its t1/2.
Therapeutic uses of Cardiac glycosides
1- Congestive heart failure: - Reserved for patients with heart failure who are in
atrial fibrillation or remain symptomatic despite therapy with ACEI.
v For initiating Digoxin therapy, begin with 0.125 0.25mg/day.
2- Atrial fibrillation with rapid ventricular response:
Blocks AV node thereby protects ventricle from rapid atrial rate.
Loading dose 1mg over 24 hours i.e. 0.25mg/6hrs I.V.
Maintenance dose 0.125mg daily.
3- Atrial flutter: - It may convert Atrial flutter to Atrial fibrillation (shorten
Effective Refractory Period), which may return to normal rhythm on withdrawal
of Digoxin.
Contraindications of Digitalis:
1- Partial heart block.
2- Hypertrophic obstructive cardiomyopathy.
3- Acute myocardial infarction.
4- Rheumatic fever.
Digitalis Toxicity
Digitalis has a low safety margin. Its cardiac toxicity is potentiated by hypokalemia and
hypercalcemia.
A- Cardiac toxicity (most frequent side effect): - Digitalis can cause every variety of
Arrhythmia:
1- Marked sinus bradycardia.
2- Second and third degree heart block.
3- Atrial tachycardia and Atrial flutter and fibrillation.
4- Ventricular premature beats, ventricular tachycardia and fibrillation.
B- Extra-cardiac toxicity:
Psychiatric: - Fatigue, Malaise, Confusion, Dizziness, Abnormal dreams.
Visual: - Blurred or Yellow vision.
GIT: - Anorexia, Nausea, Vomiting, Abdominal pain.
Treatment of Digitalis toxicity:
1- Stop the drug and the Potassium loosing diuretic.
2- Treatment of Digitalis-induced arrhythmias:
i)
Atropine for: - Bradycardia and Second or Third degree heart block.
ii)
Lidocaine for ventricular arrhythmia.
iii)
Potassium administration in tachy-arrhythmia (K+ competes with
Digitalis for Na+/K+ ATPase preventing inhibition of the enzyme by
Digitalis).
iv)
K+ administration is contraindicated in AV block.
Diuretics:
I.V administration of a Loop diuretic provides more rapid diuresis.
Initial bolus injection of 40mg Frusemide followed by 10mg/hour
infusion.
IIParenteral Vasodilators:
i)
Sodium nitroprusside (I.V):
Venous vasodilator producing decreased preload leading to decreased
pulmonary and venous congestion resulting in decreased dyspnea and
edema.
Arterial vasodilator producing decreased Arterial resistance resulting in
increased Cardiac output.
Potent with rapid onset of action 2-4 minutes.
ii)
Nitroglycerine (I.V):
Rapid and potent venular vasodilator that decreases preload producing
decreased pulmonary and venous congestion thereby decreases dyspnea
and edema.
High infusion rates producing Arterial vasodilatation leading to decreased
afterload and increased Cardiac output.
iii)
Parenteral positive inotropic drugs:
1- Dobutamine and Dopamine:
Stimulate myocardial contractility.
Dopamine has renal vasodilator effect resulting in diuresis.
Not active orally.
Reserved for management of acute Heart failure or refractoriness to
oral agents.
2- Phosphodiesterase inhibitors (Inamrinone and Milrinone):
Selective inhibitors of Phosphodiesterase enzyme resulting in
increased cAMP.
Stimulate myocardial contractility.
Induce arterial and venous dilatation.
Used I.V. for short term support in advanced heart failure.
Toxicity: - Nausea, Vomiting, Thrombocytopenia, Liver toxicity.
Milrinone is preferred because it reduces risk of thrombocytopenia and
liver toxicity.