Digoxin

Common indications

• In atrial fibrillation (AF) and atrial flutter, digoxin is used to reduce the ventricular rate. However, a β-blocker or non-dihydropyridine calcium channel blocker is usually more effective.
• In severe heart failure, digoxin is used as a third-line treatment in patients who are already taking an ACE inhibitor, β-blocker and either an aldosterone antagonist or angiotensin receptor blocker. It is used at an earlier stage in patients with co-existing AF.

 

Mechanisms of action

• Digoxin is negatively chronotropic (it reduces the heart rate) and positively inotropic (it increases the force of contraction). In atrial fibrillation and flutter its therapeutic effect arises mainly via an indirect pathway involving increased vagal (parasympathetic) tone. 
• This reduces conduction at the atrioventricular (AV) node, preventing some impulses from being transmitted to the ventricles, thereby reducing the ventricular rate. 
• In heart failure, it has a direct effect on myocytes through inhibition of Na+/K+-ATPase pumps, causing Na+ to accumulate in the cell. As cellular extrusion of Ca2+ requires low intracellular Na+ concentrations, elevation of intracellular Na+ causes Ca2+ to accumulate in the cell, increasing contractile force.

 

Important adverse effects

• Adverse effects of digoxin include bradycardia, gastrointestinal disturbance, rash, dizziness and visual disturbance (blurred or yellow vision). 
• Digoxin is proarrhythmic and has a low therapeutic index: that is, the safety margin between the therapeutic and toxic doses is narrow. A wide range of arrhythmias can occur in digoxin toxicity and these may be life threatening.

 

Warnings

• Digoxin may worsen conduction abnormalities, so is contraindicated in second-degree heart block and intermittent complete heart block. It should not be used in patients with or at risk of ventricular arrhythmias. 
• The dose should be reduced in renal failure, as digoxin is eliminated by the kidneys. 
• Certain electrolyte abnormalities increase the risk of digoxin toxicity, including hypokalaemia, hypomagnesaemia and hypercalcaemia. 
• Potassium disturbance is probably the most important of these, as digoxin competes with potassium to bind the Na+/K+-ATPase pump. 
• When serum potassium levels are low, competition is reduced and the effects of digoxin are enhanced.

 

Important interactions

• Loop and thiazide diuretics can increase the risk of digoxin toxicity by causing hypokalaemia. 
• Amiodorone, calcium channel blockers, spironolactone and quinine can all increase the plasma concentration of digoxin and therefore risk of toxicity.

Monitoring

• At least 6 hrs post-dose