Reversal of Digitalis Effects by Specific Antibodies

Abstract

Highly digoxin-specific or ouabain-specific antibodies can readily be obtained by immunizing rabbits or sheep with repeated injections of the glycoside coupled to protein carriers. By virtue of their binding capacity digoxin-specific antibodies are capable of removing digoxin concentrations from red blood cells and renal tissue specimens. As evidenced by various experiments with human erythrocytes and isolated cardiac preparations in vitro, digoxin effects are rapidly reversible in the presence of digoxin-specific antibodies. In vivo antidigoxin antibodies can protect animals from toxic digoxin effects and promptly abolish established toxic effects, associated with marked alterations of digoxin pharmacokinetics. However, due to the large molecular weight, complete antibodies cannot be eliminated via the renal route. The use of antigen-binding (Fab) fragments of digoxin-specific antibodies offer the advantage of rapid renal elimination of bound and inactivated digoxin. So far, due to potential immune reactions, the clinical use of purified digoxin-specific antibodies or Fab fragments is restricted to life-threatening accidental or suicidal digoxin or digitoxin poisoning.

Age-Related Differences in Digoxin Toxicity and its Treatment

“…Previous authors have reviewed the clinical management of digoxin toxicity (Ellen horn & Barceloux 1988;Hastreiter et al 1984) and specifically, the clinical utility of d-Fab fragments in cases of acute intoxication (Boldy et al 1984;Larbig et al 1979;Martiny et al 1988;Senger et al 1985;Smith et al 1976Smith et al , 1982Smolarz et al 1985;Sullivan 1986). In children, d-Fab has been used to successfully treat toxicity from {3-acetyldigoxin (Rossi et al 1984), oleander (Shumaik et al 1988) and digoxin.…”