Cardiotropic Drugs

Cardiotropic Drugs

used for Congestive Heart Failure and for Cardiac Arrhythmia

I. Digitalis Glycosides

Digoxin Digitoxin

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)

Toxic Adverse Effects

Nausea Vomiting Visual disturbances Cardiac effects (premature ventricular contractions PVC and atrioventricular node blockage)

Route of Administration (oral)

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

Digitoxin

Half-life 46h Therapeutic Range 9-25 ng/mL Toxic Level >25 ng/mL Important comments

Converted to active metabolite (digoxin) in the liver

II. Procainamide (Prontesyl)

Half-life Therapeutic Range Toxic Level

35h 4 10 ng/mL >12 ng/mL

Route of Administration (oral)

Important comments

Undergoes N-acetylation in the liver to form Nacetylprocainamide (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

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)

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

IV. Lidocaine (Xylocaine)

Half-life 2h Therapeutic Range 1.2 5.5 g/mL Toxic Level >5.5 g/mL

Important comments

A local anesthetic Undergoes N-dealkylation in the liver Not protein-bound Not stored in tissues

V. Propanolol (Indiral)

Half-life Therapeutic Range Toxic Level Important comments Toxic effect: Raynauds type

3h 50 100 ng/mL >100 ng/mL

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

Toxic Adverse Effects

Anticholinergic effects (>4.5 g/mL)

Dry mouth Constipation

Bradycardia Atrioventricular node blockage

Cardiac Effects (>10 g/mL)

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