1. Cardiotropic Drugs

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

3. I. Digitalis Glycosides
Digoxin
Digitoxin

4. Digoxin Mechanism of Action 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. Route of Administration (oral)
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 Toxic Adverse Effects Route of Administration (oral)
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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