Digoxin

Chapter 189 Digoxin



N. Joel Edwards, DVM, DACVIM (Cardiology)



KEY POINTS



• Beneficial effects of digoxin administration result from direct actions on cardiac muscle (increase in intracellular calcium) and indirect mediation of the autonomic nervous system.

• Net results of digoxin administration include an increase in force and velocity of myocardial systolic contraction (positive inotropic effect), decrease in activation of the sympathetic nervous and renin-angiotensin-aldosterone systems (neurohumoral deactivation effect), and reduction in heart rate and in conduction velocity through the atrioventricular node (vagomimetic effect).

• Clinically digoxin’s main uses are in treating systolic dysfunction that results in congestive heart failure (CHF), including dilated cardiomyopathy and end-stage left ventricular volume overload CHF, and for ventricular rate control in treating supraventricular tachyarrhythmias (atrial fibrillation, paroxysmal atrial tachycardia, atrial flutter).

• Common toxic side effects of digoxin include gastrointestinal disorders (vomiting, diarrhea, anorexia), azotemia, ventricular arrhythmias, and bradycardia.

• Serum digoxin levels should be monitored in all treated patients.


INTRODUCTION


Controversy has surrounded the use of digoxin since its “modern day” recognition by William Withering in 1785. Withering described the use of the foxglove plant, Digitalis purpurea (digitoxin), in treating ascites and peripheral edema in humans. Earlier reports of digitalis use can be found as far back as the thirteenth century.1 The use of digitalis glycosides has been embroiled in controversy for years. Part of the controversy is influenced by the relatively low therapeutic-to-toxic ratio of these products, including the common digitalis glycoside, digoxin, in use today. The controversy is also influenced by variations in individual response to the drug, marked variation in expression of the side effects, and difficulty in proving clinical efficacy in numerous drug trials.1 In any event, digoxin is still found on the pharmacy shelf of almost every veterinary facility in existence. It is used mainly to treat heart failure due to systolic dysfunction and to control supraventricular tachyarrhythmias.



PHARMACOLOGY


Digoxin is extracted from the leaves of the foxglove plant Digitalis lanata. The digoxin molecule is composed of a sugar and a cardenolide; its molecular formula is C41H64O14 and its molecular weight is 780.95 Da. Digoxin exists as odorless white crystals that are insoluble in water or ether, slightly soluble in alcohol, and freely soluble in pyridine. Digoxin (Lanoxin) is supplied as tablets in either 125 μg (0.125 mg) or 250 μg (0.25 mg) strengths; as capsules in (solution) 100 μg (0.1 mg) or 200 μg (0.2 mg) strengths; as an elixir of 50 μg/ml (0.05 mg/ml); or for intravenous injection as a sterile solution in 2-ml ampules at 250 μg (0.25 mg) per ml or 100 μg (0.1 mg) per ml.2


Digoxin’s mechanisms of action are multifaceted and include positive inotropic effects that are mediated through its inhibition of sodium-potassium adenosine triphosphatase pumps located on myocardial cell membranes, which results in an increase in intracellular sodium concentration. This sodium in turn is exchanged for extracellular calcium, raising the concentration of available calcium ions within the myocardial cell and thus mediating increased contractility. Digoxin also reduces sympathetic nerve activity, renin-angiotensin activity, circulating catecholamines, and regulates baroreceptor function by increasing vagal tone (vagomimetic effect). These functions are thought to beneficially counteract increases in activity of these systems seen in heart failure.1 These vagomimetic effects also decrease the rate of sinus node discharge, atrial conduction, and atrioventricular (AV) nodal conduction by prolonging conduction times and refractory periods of these tissues, thereby forming the basis for digoxin’s effectiveness at controlling ventricular response to supraventricular arrhythmias.3

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Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on Digoxin

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