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Section IIICardiovascular drugsSide effects
Digoxin has a low therapeutic ratio and side effects are not uncommon:
Cardiac – these include various arrhythmias and conduction disturbances – prema-
ture ventricular contractions, bigemini, all forms of AV block including third-degree
block, junctional rhythm and atrial or ventricular tachycardia. Hypokalaemia,
hypercalcaemia or altered pH may precipitate side effects. The ECG signs of pro-
longed PR interval, characteristic ST segment depression, T wave flattening and
shortened QT interval are not signs of toxicity.
DC cardioversion – severe ventricular arrhythmias may be precipitated in
patients with toxic levels and it is recommended to withhold digoxin for 24 hours
before elective cardioversion.
Non-cardiac – anorexia, nausea and vomiting, diarrhoea and lethargy. Visual
disturbances (including deranged red–green colour perception) and headache
are common while gynaecomastia occurs during long-term administration. Skin
rashes are rarely seen and may be accompanied by an eosinophilia.
Interactions – plasma levels are increased by amiodarone, captopril, erythromycin
and carbenoxolone. They are reduced by antacids, cholestyramine, phenytoin and
metoclopramide. Ca^2 +channel antagonists produce variable effects, verapamil
will increase, while nifedipine and diltiazem may have no effect or produce a small
rise in plasma levels.Kinetics
The absorption of digoxin from the gut is variable depending on the specific formu-
lation used, but the oral bioavailability is greater than 70%. It is about 25% plasma
and has a volume of distribution of 5–10 l.kg−^1 .Its volume of distribution is signif-
icantly increased in thyrotoxicosis and decreased in hypothyroidism. It undergoes
only minimal hepatic metabolism, being excreted mainly in the unchanged form by
filtration at the glomerulus and active tubular secretion. The elimination half-life is
approximately 35 hours but is increased significantly in the presence of renal failure.Toxicity
Plasma concentrations exceeding 2.5μg.l−^1 are associated with toxicity although
serious problems are unusual at levels below 10μg.l−^1 .Despite these figures the
severity of toxicity does not correlate well with plasma levels. However, a dose of
more than 30 mg is invariably associated with death unless digoxin-specific antibody
fragments (Fab) are used.Treatment of digoxin toxicity
Gastric lavage should be used with caution as any increase in vagal tone may precipi-
tate further bradycardia or cardiac arrest. Owing to Na+/K+ATPase inhibition, hyper-
kalaemia may be a feature and should be corrected. Hypokalaemia will exacerbate