Drugs Used in Heart Failure

23rd May, 2012

Heart Failure: Pathophysiology

• Progressive Disorder → dyspnea, fatigue, and fluid retention

• RHF → Peripheral Edema LHF → Pul. congestion, dyspnea

• Causes → MI, Arteriosclerotic HD, Valvular HD etc.

• Two types: • Systolic Failure: ↓ contractility → ↓EF• Diastolic Failure: ↓relaxation → ↓ Filling/COP →

↓ Stroke Vol.

Aim of Pharma-intervention

• ↓Preload: Diuretics, ACEI’s, ARB’s, Venodilators.

• ↓Afterload: ACEI’s, ARB’s, arteriodilators• ↑Contractility: Digoxin, β-agonists• ↓Remodeling of cardiac muscles: ACEI’s,

ARB’s, Spironolactone.

Inotropes: Cardiac Cell

Inotropes: Intro

• ↑Contractility→↑COP Cytosolic Ca ↑• Cardiac Glycosides~ Digitalis • Positive Inotropic from Na/Ca ion flow• Low Therapeutic Index• Most widely used in Digoxin

Indications and Side Effects

• Indications:• CHF• Supraventricular Tachycardias

• Side Effects:• Earlier: Anorexia, Nausea, Vomiting, ECG Changes• Later: Headache, Confusion, Disorientation, Visual

(Halos, Blurred vision)• Toxicity: Dysarrythmias

β-Adrenoceptor Stimulants

• β1 agonist Dobutamine → ↑cAMP → ↑Ca→ +ve inotropic effect → ↑ COP↓Ventricular Filling. I/V for Acute HF

• Dopamine

ACEI’s

Diuretics

• No effect on Contractility. ↓Venous Return→↓Preload →↓Remodeling →Better pump action. ↓plasma volume→↓ afterload →↓bp

• Thiazides; relatively mild. Ineffective in renal insufficiency.

• Loop Diuretics: Cause more elaborate diuresis with risk of hypovolemia and hypokalemia.

Diuretics

• Spironolactone: Aldo antagonist→↓Salt retention↓myocardial hypertrophy↓Hypokalemia.

• Aldosterone ~ myocardial & Vascular Fibrosis+ Baroreceptor Dysfunction

Vasodilators

• Nitrates, Hydralazine, Isosorbide dinitrate: • Venodilation (↓Preload) &/or Arteriodilation (↓

Afterload).• Long-term use →↓Remodeling

β-Blockers

• -ve inotropes. Improved systole+Reverse cardiac remodeling b/c:

• Preempt chronic sympathetic activation.• Upregulation of receptors• ↓ed Heart Rate• Block deleterious effects of norepinephrine on

myocytes→↓remodeling, hypertrophy & cell death.

• Bisoprolol, carvedilol, and metoprolol Approved for use in stable severe HF

• Low dose ~ titration

Order of Therapy