drugs used in heart failure
TRANSCRIPT
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Drugs Used in Heart Failure
23rd May, 2012
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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.
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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.
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Inotropes: Cardiac Cell
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Inotropes: Intro
• ↑Contractility→↑COP Cytosolic Ca ↑• Cardiac Glycosides~ Digitalis • Positive Inotropic from Na/Ca ion flow• Low Therapeutic Index• Most widely used in Digoxin
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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
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β-Adrenoceptor Stimulants
• β1 agonist Dobutamine → ↑cAMP → ↑Ca→ +ve inotropic effect → ↑ COP↓Ventricular Filling. I/V for Acute HF
• Dopamine
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ACEI’s
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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.
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Diuretics
• Spironolactone: Aldo antagonist→↓Salt retention↓myocardial hypertrophy↓Hypokalemia.
• Aldosterone ~ myocardial & Vascular Fibrosis+ Baroreceptor Dysfunction
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Vasodilators
• Nitrates, Hydralazine, Isosorbide dinitrate: • Venodilation (↓Preload) &/or Arteriodilation (↓
Afterload).• Long-term use →↓Remodeling
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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
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Order of Therapy