Digoxin and the Cardiac Glycosides

Cardiac glycosides include digoxin, digitoxin, digitalis and ouabain. Of these, only digoxin is in regular use in the UK. Prescribing digoxin is is not difficult providing certain principles are followed.

Digoxin acts by increasing sodium/calcium exchange. This has the effect of increasing intracellular calcium levels which, in myocardial muscle, has the effect of enhancing the strength of contraction (positive inotropism). It also affects the electrical physiology of the heart, blocking AV conduction and reducing the heart rate by enhancing vagal nerve activity (negative chronotropy).

Atrial fibrillation

The principle indication is permanent/persistent atrial fibrillation with a fast ventricular rate. The target should be a resting ventricular rate of approximately 90/minute. It should be considered as monotherapy primarily for sedentary patients. Beta blockers or rate-limiting calcium-channel blockers are more effective for monotherapy in patients likely to undergo exertion.¹

Supraventricular tachycardia

Digoxin is most commonly used in this situation in children with congenital heart disease. It is given intravenously in the acute situation to slow the heart rate.

Heart failure

NICE guidance suggests that digoxin should be used as first-line in patients with atrial fibrillation who also have co-existing heart failure. In all other cases where heart failure is due to left ventricular dysfunction it should be reserved for patients in whom the condition has worsened despite the use of ACE inhibitors, beta blockers and diuretic therapy.²

• For patients with atrial fibrillation and flutter, digoxin works best when a high dose is given as an initial loading dose (rapidly digitalisation).
• A loading dose should be given of 15 mcg/kg of lean body weight. For a woman with a lean body weight of 50 kg this would work out at a total dose of 15 x 50 = 750 mcg. Lean body weight is defined as total body mass minus fat mass. There are a number of methods of determining this but where it is clinically significant the simplest method in primary care is the use of skin calipers.⁴
• The range is usually 750-1500 mcg in over a 24-hour period. It is commonly given orally and rarely intravenously. The dose is given once-daily except in elderly patients in whom it should be given in divided doses over a 6-hourly period. If the ventricular rate does not reduce to the desired target, an additional dose of 5 mcg/kg can be given, providing there are no symptoms or signs of toxicity (see below under 'Monitoring'). If the rate does not come down after a further dose, another drug should be given.
• Slow loading may be more appropriate, depending on the clinical state of the patient and the urgency of the condition. It can be achieved by giving 250 to 750 micrograms daily for 1 week followed by an appropriate maintenance dose. A clinical response should be seen within one week.
• In the rare patient with atrial fibrillation or flutter who requires emergency digitalisation, intravenous infusion can be used. The dose is 0.75-1 mg over at least 2 hours, then a maintenance dose by mouth on the following day.
• Heart failure (patients in sinus rhythm) should be given 62.5-125 mcg by mouth once daily. No loading dose is required.

The maintenance dose is calculated as a fraction of the effective loading dose, adjusted for renal function.

Monitoring is important both to ensure that the correct dosage is being given and also that factors which might provoke toxicity, e.g. renal dysfunction and hypokalaemia, are not developing. Features suggestive of toxicity include nausea, vomiting, diarrhoea, dyspnoea, confusion, dizziness, headache, blurred vision and diplopia. See the BNF for the full list.⁵

Urea and electrolytes should be monitored. In stable patients this may be done annually but if there is any change in dosage or clinical status more regular monitoring should be performed.

The best monitor of response to treatment in atrial fibrillation is ventricular rate. Plasma concentrations can however be helpful when initiating therapy, checking compliance or detecting toxicity. A target range of 1.0-1.5 nml/l should be aimed for but concentrations of 2 nm/l may be required in atrial fibrillation. Levels above 2 nm/l suggest toxicity. Plasma potassium should be measured in all cases of suspected toxicity. If hypokalaemia is evident, the drug should be withheld irrespective of the digoxin level.

For details of contra-indications and interactions, see the BNF.⁵