Management of Ahf

AIM OF MANAGEMENT:

• Decreasing congestive symptoms (with diuretics).
• Increasing contractility (with positive inotropic agents).

1. Diuretics:

• Pathophysiology:
  • In heart failure, fluid accumulation in lungs & peripheral organs –> Causes congestive symptoms.
• MOA: 
  • Diuretics decrease congestive symptoms by edema fluid mobilization.
  • DOC – Loop diuretics (furosemide & bumetanide)
• Drug effects:
  • Possess high ceiling diuretic effect.
  • Decrease preload.
  • Reduce congestive symptoms. 
  • Produce venodilation prior to diuresis –> Immediate relief from dyspnea in pulmonary edema.
• Adverse effects:
  • Development of tolerance (chronic use) – Prevented by combination with thiazides or spironolactone.
  • Spironolactone decreases mortality.

2. Inotropic drugs:

• Important drugs: Dobutamine, dopamine, inodilators & cardiac glycosides.
• Used for short-term management of acute CHF (except digoxin used orally for maintenance also).
• Dobutamine
  • Selective ß1 agonist.
  • No effect on dopamine receptors.
  • Given as i.v. infusion.
• Drug actions:
  • Increases cAMP in heart –> increases cardiac contractility –> increases output.
• Dopamine
  • Acts on dopamine, ß and α receptors depending on drug concentration.
  • At dose 1-2µg/kg/min – Stimulates only dopamine receptors & causes renal vasodilation.
  • Intravenous infusionrate of 2-10µg/kg/min –  Stimulates heart by ß1 agonistic action.
  • Higher dose (>10µg/kg/min) – Intense vasoconstriction.

3. Cardiac Glycosides

• Drugs included: 
  • Digoxin, digitoxin, strophanthin & ouabain.
  • Collectively known as digitalis.
• Digitalis – 
  • Only oral inotropic drug.
  • Positive inotropic drug.
• Uses:
  • Treatment of atrial fibrillation, atrial flutter & paroxysmal supraventricular tachycardia.
  • Used as acute treatment of CHF & for maintenance (digoxin).
• Disadvantages:
  • Decreases heart rate or oxygen consumption (unlike other inotropic drugs).
  • Do not alter basic pathology.
  • Inability to decrease mortality.

4. Inodilators

• Drugs included: Inamrinone (previously amrinone), milrinone & vesnarinone.
• MOA: 
  • Inhibits phosphodiesterase III enzyme –> increases cAMP in heart & blood vessel –> cAMP increases transmembrane Ca+ influx in myocardial cells –> increases contractility –> vascular smooth muscle relaxation (vasodilation/inotrophic).
• Uses: 
  • Severe & refractory CHF – Short term i.v. use.
• Adverse effect:
  • Thrombocytopenia – Mainly with inamrinone.
    • Less with milrinone (hence preferred).
  • Both cause arrhythmias.

5. Levosimendan:

• Inhibits phosphodiesterase & sensitizes myocardium to Ca+.

6. Nesiritide:

• Recombinant BNP.
• BNP:
  • Brain-derived natriuretic peptide.
  • Secreted by ventricles.
  • Used as i.v. for acute CHF associated with dyspnoea at rest.
• Helps differentiating cardiac from pulmonary causes of dyspnoea.
• Increases cGMP & causes vasodilation.
• Increases renal sodium excretion.
• Metabolism:
  • Short half-life.
  • Limiting factor: Its breakdown by neutral endopeptidase (NEP) enzyme.
• Ecadotril – NEP enzyme inhibitor.

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