Lecture on Drugs for Congestive Cardiac Failure

Basic Problems in Cardiac Failure

• Patient with cardiac failure has issues with heart not pumping efficiently.
• Understanding the normal heart function helps to identify drug treatments.

Frank-Starling Law

• States that more the ventricle is filled with blood, the stronger it contracts within physiological limits.
• Increased ventricular filling leads to increased end-diastolic volume (EDV) and contractility.

Healthy Heart Function

• Normal heart operates at around 140 ml EDV, ejecting 70 ml (stroke volume).
• Increased venous return leads to increased cardiac output (CO).

Failing Heart Function

• Decreased contractility due to disease (e.g., ischemic heart disease) reduces CO.
• Leads to higher EDV, but less effective contraction.

Compensation Mechanisms in Failing Heart

• Sympathetic nervous system activation increases heart rate and contractility initially but poses long-term risks.
• Renin-Angiotensin-Aldosterone System (RAAS) is activated, causing vasoconstriction and fluid retention.

LaPlace's Law

• Pressure generated by the heart is proportional to wall tension and inversely proportional to the radius of the ventricle.
• Failing heart experiences increased radius and stress, reducing effective pressure generation.

Treatment Goals

• Reduce preload (volume of blood in the ventricle at end-diastole), using diuretics and vasodilators (e.g., ACE inhibitors, ARBs).
• Reduce afterload (resistance against which the ventricle must work), using arterial dilators.
• Improve contractility using positive inotropic drugs when necessary (e.g., Digoxin, Dopamine, Dobutamine).

Specific Treatments

Diuretics

• Used to reduce blood volume and preload.
• Types: Thiazides (mild diuretics), Loop Diuretics (strong diuretics like Furosemide), K+-sparing diuretics (e.g., Spironolactone).

ACE Inhibitors and ARBs

• Reduce preload by decreasing salt and water retention.
• Reduce afterload by vasodilation.
• Maintain/manage RAAS to prevent pathological remodeling of the heart.

Positive Inotropic Drugs

• Digoxin: Increases intracellular calcium, improves contractility.

  • Used in severe systolic dysfunction, CHF with atrial fibrillation.
  • Needs careful monitoring for toxicity.

• Dopamine: Stimulates beta1-adrenergic receptors, used in severe, hypotensive heart failure.

• Dobutamine: Primarily beta1 agonist, used without hypotension.

• Phosphodiesterase Inhibitors (e.g., Amrinone, Milrinone): Short-term use in severe heart failure, increase cyclic AMP.

Side Effects and Complications

Digoxin Toxicity

• Presents with symptoms like nausea, confusion, and arrhythmias (atrial or ventricular tachycardia with AV blocks).
• Careful monitoring of electrolyte levels (potassium, magnesium, calcium) is crucial.
• Treated by stopping the drug, correcting electrolytes, using antiarrhythmic drugs (Phenytoin, Lidocaine), Atropine for bradycardia, temporary pacing for heart blocks, and Digibind antibodies for severe cases.

Dopamine and Dobutamine

• Risk of receptor downregulation when used long-term.
• Primarily used for acute phases.

Phosphodiesterase Inhibitors

• Limited to short-term use due to the risk of increased mortality with long-term use.

Concluding Recommendations

• Initial management with ACE inhibitors, ARBs, and diuretics to reduce preload and afterload, improve survival, and reverse pathological changes.
• Reserve Digoxin and inotropic agents for severe and specific cases of heart failure with close monitoring for toxicity.