Digoxin

Question 1

Drug class?

Answer 1

Cardiac Glycosides

Question 2

How does it work?

Answer 2

The pharmacological receptor of digoxin is the membrane bound cation dependent Na+,K+ATPase. Digoxin binds to this enzyme and inhibits it, resulting in an increase in the intracellular concentration of calcium which, in turn, alters the intracellular disposition of calcium.

The effect of digitalis on intracellular calcium concentrations results in an increase in the force and velocity of myocardial systolic contraction (i.e. a positive inotropic effect on myocardial cells). Digoxin has a negative chronotropic effect as it slows the overall heart rate. These actions result in a decrease in the rate of contractility, particularly through the atrioventricular node, with subsequent effects on atrial fibrillation. Digoxin also has complex direct effects on conduction velocities and refractory periods of the conducting fibres in cardiac muscle. In addition to its direct effects, digoxin acts indirectly by increasing vagal input through direct vagal stimulation and decreasing sympathetic drive. These effects contribute to the slowing of the ventricular rate by digoxin, both in sinus rhythm and in atrial fibrillation

Question 3

Indications?

Answer 3

• Digoxin is indicated for the treatment of congestive cardiac failure.
• Digoxin may be used for certain supraventricular dysrhythmias, particularly atrial fibrillation.

Question 4

Contra-indications?

Answer 4

• Patients with arrhythmias caused by cardiac glycoside intoxication.
• Patients with hypertrophic obstructive cardiomyopathy, unless there is concomitant atrial fibrillation and heart failure, but even then caution should be exercised if digoxin is to be used.
• Patients with supraventricular arrhythmias associated with an accessory atrioventricular pathway, as in the Wolff-Parkinson-White syndrome, unless the electrophysiological characteristics of the accessory pathway and any possible deleterious effect of digoxin on these characteristics have been evaluated. If an accessory pathway is known or suspected to be present and there is no history of previous supraventricular arrhythmias, digoxin is similarly contraindicated.
• Patients with intermittent complete heart block or second degree atrioventricular block, especially if there is a history of Stokes-Adams attacks.
• Patients with ventricular tachycardia or ventricular fibrillation.

Question 5

Side-effects?

Answer 5

• Common: nausea, vomiting, anorexia, diarrhoea, visual disturbances
• Rarely: confusion, hallucinations

Question 6

Possible interactions?

Answer 6

• Amiodarone/propafenone/quinidine: antiarrhythmics  risk of digoxin toxicity
• Ca channel blockers:  risk of digoxin toxicity
• Diuretics: hypokalaemia can  risk of toxicity