Digoxin and Other Cardiac Glycosides
Cardiac glycosides and related cardenolides are found in several plants, including digitalis, oleander, foxglove, lily of the valley, red squill, and rhododendron, and in toad venom (Bufo species), which may be found in some Chinese herbal medications and herbal aphrodisiacs. Cardiac glycosides are used therapeutically in tablet form as digoxin and digitoxin. Digoxin is also available in liquid-filled capsules with greater bioavailability.
Mechanism of toxicity
Cardiac glycosides inhibit the function of the sodium-potassium-ATPase pump. After acute overdose, this results in hyperkalemia (with chronic intoxication, the serum potassium level is usually normal or low owing to concurrent diuretic therapy).
Direct effects and potentiation of vagal tone result in slowing of the sinus rate and decreased sinus and atrioventricular (AV) node conduction velocity.
Increased atrial and ventricular automaticity occurs because of accumulation of intracellular calcium, enhanced diastolic depolarization, and development of afterdepolarizations. These effects are augmented by hypokalemia and hypomagnesemia.
Pharmacokinetics. The bioavailability of digoxin ranges from 60–80%; for digitoxin, more than 90% is absorbed. The volume of distribution (Vd) of digoxin is very large (5–10 L/kg), whereas for digitoxin the Vd is small (˜0.5 L/kg). Peak effects occur after a delay of 6–12 hours. The elimination half-life of digoxin is 30–50 hours, and for digitoxin it is 5–8 days (owing to enterohepatic recirculation; see also Table II–61).
Drug interactions. A number of drugs that are often co-administered with digitalis inhibit its metabolism, increase serum levels, and may induce toxicity. These include amiodarone, verapamil, quinidine, macrolide antibiotics, and others.
Toxic dose. Acute ingestion of as little as 1 mg of digoxin in a child or 3 mg of digoxin in an adult can result in serum concentrations well above the therapeutic range. More than these amounts of digoxin and other cardiac glycosides may be found in just a few leaves of oleander or foxglove. Generally, children appear to be more resistant than adults to the cardiotoxic effects of cardiac glycosides.
Clinical presentation. Intoxication may occur after acute accidental or suicidal ingestion or with chronic therapy. Signs and symptoms depend on the chronicity of the intoxication.
With acute overdose,
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