Cardiac glycosides - Therapeutic use, adverse effects and interactions
The essential therapeutic use of digoxin which is more used than digitoxin is the treatment of cardiac failure. Digoxin improves the cardiac function and decreases the frequency of hospitalizations without delaying mortality. The second therapeutic use of digoxin is the treatment of supra-ventricular arrhythmias, particularly atrial fibrillation.
The initial dosage, generally high and called loading dosage, is followed by a lower dosage, called maintenance dosage. It is advised to control the plasma level of digoxin to reach the best dosage.
The majority of adverse effects of digoxin and other cardiac glycosides are dose-related. It is thus essential, when an undesirable effect is suspected, to control blood concentrations. Moreover its adverse effects in women seem more marked (increased mortality) than in men, which does not encourage to prescribe digoxin to women with congestive heart failure.
See Sex-Based Differences in the Effect off Digoxin for the Treatment of Heart Failure.
- digestive disorders: frequently, anorexia, nausea, vomiting, salivation; more rarely, diarrhea or constipation and stomach pains.
- neurosensory disorders: frequently, headache, insomnia, sometimes confusions, depression, dizziness, visual disturbances of colors, micropsy or macropsy, amblyopia, pain (neuralgia of the trigeminal nerve), seizures, paresthesias, delirium.
- cardiac manifestations, generally linked to an overdose and beginning generally by bradycardia, then extrasystoles, tachycardia or fibrillation.
- endocrine adverse effects, such as gynecomastia in men, related to the steroid structure of cardiac glycosides which can have metabolites with an estrogen effect.
The treatment of poisoning by cardiac glycoside involves first the cessation of the glycoside, possibly the use of a drug able to reduce digitalis effects: potassium in case of hypokalemia, atropine in case of bradycardia, lidocaine, chelating agent of calcium, or electric stimulation.
In severe overdose, digoxin-specific antibody fragments can be used to neutralize circulating free digoxin by binding to it. This neutralization induces a displacement of digoxin from tissues towards plasma where it is neutralized. The beneficial effects of the antibody administration appear quickly, in less than one hour, but can last less long than the effects of digoxin with reappearance of the signs of poisoning. These relapses are seen in case of administration of an insufficient antibody dose. The administration of digoxin-specific antibody fragments can elicit allergic reactions.
A certain number of interactions between cardiac glycosides and other drugs were described:
Among other drugs having a positive inotropic effect by mechanisms of action different from that of digoxin there are milrinone, inhibitor of phosphodiesterases, and sympathomimetics such as dobutamine and dopexamine.
Beta-1 adrenergic agonists.