Guide to Cardiotropic Drugs: Usage, Mechanism of Action, and Adverse Effects

1. Cardiotropic Drugs

2. Cardiotropic Drugs • used for Congestive Heart Failure and for Cardiac Arrhythmia

3. I. Digitalis Glycosides • Digoxin • Digitoxin

4. Digoxin • Half-life 35 – 40 h • Therapeutic Range 0.5 – 2 ng/mL • Toxic Level >2 ng/mL • Mechanism of Action • Functions by inhibiting membrane Na+, K+ -ATPase (causes a decrease in intracellular potassium, resulting in increased intracellular calcium in cardiac contractility)

5. Toxic Adverse Effects • Nausea • Vomiting • Visual disturbances • Cardiac effects (premature ventricular contractions – PVC and atrioventricular node blockage) • Route of Administration (oral)

6. Important comments • elimination of digoxin occurs primarily by renal filtration of the plasma free form • in circulation, 25% is protein-bound and the rest is sequestered into muscle cells • its therapeutic actions and toxicities is influenced by the concentration of serum electrolytes (low serum potassium and magnesium potentiate digoxin actions) • Thyroid status also influence the action of digoxin: • Hyperthyroid patients: resistance • Hypothyroid patients: more sensitive

7. Digitoxin • Half-life 4 – 6 h • Therapeutic Range 9-25 ng/mL • Toxic Level >25 ng/mL • Important comments • Converted to active metabolite (digoxin) in the liver

8. II. Procainamide (Prontesyl) • Half-life 3 – 5 h • Therapeutic Range 4 – 10 ng/mL • Toxic Level >12 ng/mL • Route of Administration (oral)

9. Important comments • Undergoes N-acetylation in the liver to form N-acetylprocainamide (NAPA) which is the active metabolite • Toxic side effects related to Systemic Lupus Erythematosus (SLE) • Gastrointestinal absorption is rapid and complete • Absorbed procainamide is about 20% bound to plasma proteins • Its active metabolite can be measured by immunoassay

10. III. Quinidine • Half-life 5 – 12 h • Therapeutic Range 2.3 – 5 ng/mL • Toxic Level >5 ng/mL • Toxic Adverse Effects • Nausea • Vomiting • Abdominal discomfort • Route of Administration (oral)

11. Important comments • Measured fluorometrically (common) • May also be determined by chromatography and immunoassay • Undergoes hydroxylation in the liver • Two most common formulations: • Quinidine sulfate (gastrointestinal absorption is complete and rapid) • Quinidine gluconate • Absorbed quinidine is 70 – 80% bound to serum proteins • Elimination is through hepatic metabolism

12. IV. Lidocaine (Xylocaine) • Half-life 2 h • Therapeutic Range 1.2 – 5.5 µg/mL • Toxic Level >5.5 µg/mL • Important comments • A local anesthetic • Undergoes N-dealkylation in the liver • Not protein-bound • Not stored in tissues

13. V. Propanolol (Indiral) • Half-life 3 h • Therapeutic Range 50 – 100 ng/mL • Toxic Level >100 ng/mL • Important comments • Toxic effect: Raynaud’s type

14. VI. Disopyramide • Important comments • Commonly used as quinidine substitute when quinidine adverse effects are excessive • Orally administered • Gastrointestinal is complete and rapid • Eliminated by renal filtration, and to a lesser extent, by hepatic metabolism

15. Toxic Adverse Effects • Anticholinergic effects (>4.5 µg/mL) • Dry mouth • Constipation • Cardiac Effects (>10 µg/mL) • Bradycardia • Atrioventricular node blockage

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