Cardiac glycosides

Question 1

Indications

Answer 1

1. 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.
2. 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.

Question 2

Mechanisms of action

Answer 2

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.

Question 3

Adverse effects

Answer 3

bradycardia
gastrointestinal disturbance
rash
dizziness 
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.

Question 4

Warnings

Answer 4

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.

Question 5

Interactions

Answer 5

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.

Question 6

Prescribing

Answer 6

Digoxin is available as an oral or intravenous preparation. The effect of IV digoxin is seen at about 30 minutes, compared to about 2 hours following an oral dose.

Question 7

Administration

Answer 7

Oral digoxin can be taken with or without food. Intravenous doses must be given slowly.

Question 8

Communication

Answer 8

Explain that you are offering a treatment which, as applicable, should slow down their abnormally fast heart rhythm and make their heart beat more strongly. You should warn your patient of common side effects such as sickness, diarrhoea and headache. Ask them to seek advice if side effects are particularly bad or seem to get progressively worse, as this may suggest the dose is too high.