DIGOXIN - digoxin tablet West-ward Pharmaceutical Corp. ---------- DIGOXIN TABLETS, USP Revised 05/08 Rx Only
CLINICAL PHARMACOLOGY
MECHANISM OF ACTION
Mechanism of Action: Digoxin inhibits sodium-potassium ATPase, an enzyme that regulates the quantity of sodium and potassium inside cells. Inhibition of the enzyme leads to an increase in the intracellular concentration of sodium and thus (by stimulation of sodium-calcium exchange) an increase in the intracellular concentration of calcium. The beneficial effects of digoxin result from direct actions on cardiac muscle, as well as indirect actions on the cardiovascular system mediated by effects on the autonomic nervous system. The autonomic effects include: (1) a vagomimetic action, which is responsible for the effects of digoxin on the sinoatrial and atrioventricular (AV) nodes; and (2) baroreceptor sensitization, which results in increased afferent inhibitory activity and reduced activity of the sympathetic nervous system and renin-angiotensin system for any given increment in mean arterial pressure. The pharmacologic consequences of these direct and indirect effects are: (1) an increase in the force and velocity of myocardial systolic contraction (positive inotropic action); (2) a decrease in the degree of activation of the sympathetic nervous system and renin-angiotensin system (neurohormonal deactivating effect); and (3) slowing of the heart rate and decreased conduction velocity through the AV node (vagomimetic effect). The effects of digoxin in heart failure are mediated by its positive inotropic and neu-rohormonal deactivating effects, whereas the effects of the drug in atrial arrhythmias are related to its vagomimetic actions. In high doses, digoxin increases sympathetic outflow from the central nervous system (CNS). This increase in sympathetic activity may be an important factor in digitalis toxicity.
PHARMACOKINETICS SECTION: ABSORPTION
PHARMACODYNAMICS SECTION
INDICATIONS AND USAGE
CONTRAINDICATIONS:
WARNINGS
WARNINGS:Sinus Node Disease and AV Block: Because digoxin slows sinoatrial and AV conduction, the drug commonly prolongs the PRinterval. The drug may cause severe sinus bradycardia or sinoatrial block in patients with preexisting sinus node disease and maycause advanced or complete heart block in patients with preexisting incomplete AV block. In such patients consideration should begiven to the insertion of a pacemaker before treatment with digoxin.Accessory AV Pathway (Wolff-Parkinson-White Syndrome): After intravenous digoxin therapy, some patients with paroxysmalatrial fibrillation or flutter and a coexisting accessory AV pathway have developed increased antegrade conduction across theaccessory pathway bypassing the AV node, leading to a very rapid ventricular response or ventricular fibrillation. Unless conductiondown the accessory pathway has been blocked (either pharmacologically or by surgery), digoxin should not be used in such patients.The treatment of paroxysmal supraventricular tachycardia in such patients is usually direct-current cardioversion.Use in Patients with Preserved Left Ventricular Systolic Function: Patients with certain disorders involving heart failureassociated with preserved left ventricular ejection fraction may be particularly susceptible to toxicity of the drug. Such disordersinclude restrictive cardiomyopathy, constrictive pericarditis, amyloid heart disease, and acute cor pulmonale. Patients with idiopathichypertrophic subaortic stenosis may have worsening of the outflow obstruction due to the inotropic effects of digoxin.