Digoxin

Digoxin

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Cardiac glycosides have been used for over two centuries to treat heart failure. The only commonly used cardiac glycoside in Australia is digoxin. It has a reduced role in the treatment of heart failure because of the proven efficacy of ACE inhibitors. Digoxin is also used to control ventricular rate in the management of atrial fibrillation or flutter.

Digoxin has a significant positive inotropic effect, principally by inhibiting sodium/potassium adenosine triphosphatase (ATPase) leading to increased intracellular concentrations of sodium and calcium. It has complex effects on the electrical activity of cardiac myocytes. Of clinical importance, digoxin slows sinoatrial node discharge and delays conduction through the atrioventricular node, largely by increasing vagal and diminishing sympathetic influence.

Digoxin is variably absorbed after oral administration and has a half-life of 36 to 48 hours in the presence of normal renal function. It is predominantly excreted renally, hence its half-life is prolonged in renal impairment. Digoxin has a long distribution phase of approximately 6 hours following oral or intravenous administration.

Dosing and monitoring: Dosage of digoxin should be adjusted according to therapeutic effects and plasma concentration, particularly in patients with renal impairment, and in the elderly, in whom serum creatinine can be normal despite a substantial loss of renal function. Blood for monitoring should be taken immediately before a dose or at least six hours after a dose to allow for digoxin's long distribution phase. A loading dose is used in the treatment of arrhythmias, but is not usually required when treating heart failure. A suitable loading dose is 12 to 15 times the body weight in kilograms (use the lower factor in patients with renal dysfunction) in people with normal volume of distribution, with the result expressed in micrograms and rounded up to the nearest 125 micrograms. This is given orally as two half doses separated by 2 hours, or as an IV bolus if the oral route is not available. An initial maintenance dose can be calculated as outlined in Box 3.1.

Adverse effects: The most serious manifestation of digoxin toxicity is its potential to cause arrhythmias. Anorexia, nausea, vomiting, diarrhoea and central nervous system changes are also seen. Toxic effects may occur, even when the plasma concentration is within the therapeutic reference range, particularly in patients with cor pulmonale with acidosis and hypoxaemia, and in patients with hypokalaemia and hypomagnesaemia.

Calculation of digoxin maintenance dose (Box 3.1)

A.	Calculate the approximate creatinine clearance by using the modified Cockcroft-Gault formula:
	Adult males:	creatinine clearance (mL/min) =	(140 - age) x ideal weight (kg)
			0.814 x serum creatinine (micromol/L)
	Adult females:	multiply the above equation by 0.85
	(In applying the formula, similar figures in the numerator and denominator can be cancelled to simplify the calculation.)
	or alternatively you can use the Creatinine clearance and ideal body weight calculators.
B.	Multiply the calculated creatinine clearance by 2 and add 50 to this result.
C.	An initial maintenance dose in micrograms is given by: for patients greater than 70 kg, round up the result of B (above) to the nearest multiple of 62.5 micrograms of digoxin for patients less than 70 kg, round down the result of B (above) to the nearest multiple of 62.5 micrograms of digoxin