Cardiovascular System Lecture

Main Topics

1. Hypertension
2. Congestive Heart Failure (CHF)
3. Angina
4. Arrhythmias
5. Anti-lipidemic Drugs

Congestive Heart Failure (CHF)

• Definition: Inability of the heart to pump blood adequately.
• Heart has four chambers:
  • Left Ventricle: Pumps blood to the body.
  • Right Ventricle: Pumps blood to the lungs.
• Left Ventricular Failure:
  • Blood accumulates in the lungs -> Pulmonary edema.
• Right Ventricular Failure:
  • Blood accumulates in the liver -> Hepatic congestion, increased jugular venous pressure.
• Aim of Treatment:
  • Remove excess fluid (Diuretics).
  • Increase heart's pumping activity (Inotropic drugs).

Diuretics

• Loop Diuretics (e.g., Furosemide):
  • Strong, high efficacy (removes large amounts of fluid).
  • Short acting.
• Thiazides:
  • Weaker, long acting, used in hypertension.
• Common Side Effects:
  • Loss of sodium and water -> Hyponatremia
  • Loss of potassium, hydrogen, magnesium -> Hypokalemia, metabolic alkalosis, hypomagnesemia.
  • Increase in blood sugar, lipids, uric acid -> Hyperglycemia, hyperlipidemia, hyperuricemia.
  • Calcium effect:
    • Loop Diuretics: Hypocalcemia
    • Thiazides: Hypercalcemia

Inotropic Drugs

• Beta-1 Agonists (Dopamine, Dobutamine, etc.):
  • Stimulate heart to increase contractility.
  • Work by increasing cyclic AMP.
• Phosphodiesterase Inhibitors (Amrinone, Milrinone):
  • Increase cyclic AMP by inhibiting its breakdown.
  • Effects: Inotropic and vasodilatory (Inodilators)
• Digitalis (Digoxin):
  • Mechanism: Inhibits Na-K ATPase, increases intracellular calcium.
  • Effects: Increases contractility without increasing heart rate.
  • Uses: CHF, Atrial fibrillation (Decreases conduction from atrium to ventricle).

Digitalis Toxicity

• Most common adverse effects:
  • GI: Nausea, vomiting
  • Arrhythmias: Ventricular bigeminy (most common arrhythmia), non-paroxysmal atrial tachycardia with AV block (most characteristic)
• Factors increasing risk:
  • Hypercalcemia, Hypokalemia, Hypomagnesemia
  • Drug interactions: Quinidine, Verapamil, Amiodarone, Thiazides
  • Renal failure increases Digoxin toxicity
• Management:
  • Correct metabolic disturbances
  • Antiarrhythmic drug: Lidocaine
  • Severe cases: Digibind (antibody against Digitalis)

Chronic CHF

• Aim of Treatment:
  • Reduce work of heart (Vasodilators: Nitrates, Hydralazine, ACE inhibitors, ARBs)
  • Remove fluid (Diuretics)
  • Reverse left ventricular hypertrophy (Beta-blockers, ACE inhibitors, ARBs, Aldosterone antagonists)
• Vasoactive Drugs:
  • Nitrates: Decrease preload
  • Hydralazine: Decrease afterload
• Beta-blockers (Carvedilol, Metoprolol, Bisoprolol):
  • Indicated in CHF, decrease mortality
  • Contraindicated in acute CHF
• Aldosterone Antagonists (Spironolactone, Eplerenone):
  • Reduce mortality, potassium-sparing diuretics

New Drugs in CHF

• Nesiritide: Recombinant BNP for acute CHF (IV, short-acting)
• NEP Inhibitors: Increase BNP (Sacubitril)
• Vasopeptidase Inhibitors: Inhibit both ACE and NEP
• ARNIs: ARB with NEP inhibitor (Valsartan + Sacubitril)
• Ivabradine: Decreases heart rate by blocking funny current in SA node
• Vasopressin Antagonists (Vaptans): Conivaptan (IV), Tolvaptan (Oral)
  • Used for vasodilation and increased diuresis

This lecture covered a comprehensive overview of congestive heart failure, including its pathogenesis, treatment aims, specific drugs used, their mechanisms, side effects, and some newer treatment methods.