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Drug Interactions with Digitalis Glycosides

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Summary

The 2 major factors affecting serum levels of the most commonly used cardiac glycoside digoxin, are patient compliance and the physical characteristics of the tablet; the latter is unimportant with the lipid soluble glycosides digitoxin and β-methyldigoxin. Several drugs interfere with the absorption of these cardiac glycosides from the gastrointestinal tract, either by adsorption, altering gut motility or other unknown mechanisms, but only mixtures containing kaolinpectin (and possibly some liquid antacids) are of potential clinical importance with tablets of a satisfactory dissolution profile.

Enzyme inducing agents can increase the rate of elimination of digitoxin and heparin-induced free fatty acid release decrease protein binding of digitoxin, but the therapeutic implications are not clear.

The biological action on the heart depends on the amount of glycoside in the myocardial tissue and the reaction of the patient’s diseased heart to the drug. Experimental work on tissue glycoside concentration is of great fundamental interest but of unknown clinical relevance, except for digoxin antibodies which are the most specific remedy for poisoning in attempts at suicide.

In the absence of specific electrocardiographic changes in digitalis overdosage, estimation of serum concentrations are mandatory. The role of hypokalaemia in digitalis toxicity is, in the author’s opinion, controversial but the role of some drugs in altering myocardial sensitivity to cardiac glycosides is important.

Interest in drug interactions with cardiac glycosides was initially raised by studies conducted in New York by Lindenbaum et al. (1971) who showed that serum digoxin levels in patients varied widely and were dependent on the particular brand of digoxin tablet. About this time, a senior hospital physician was under my care with uncontrolled atrial fibrillation; treatment with the hospital 0.25mg tablet of digoxin resulting in a zero plasma digoxin level (Binnion, 1974a). In this very practical way, we were lead into exploring factors affecting the bioavailability of digoxin. Bioavailability is concerned with the amount of a drug reaching the systemic circulation from a dosage form and has been investigated very extensively in the case of digoxin.

The term digitalis refers to steroid or steroid glycoside compounds that exert typical positive inotropic and electrophysiological effects on the heart. Over 300 compounds with these characteristics exist and all contain a steroid nucleus with a 5-or 6-membered unsaturated lactone ring attached to the C17 position (fig. 1). The double-bond of the lactone ring is essential for cardiac action, the structural requirements for activity are present in aglycones (e.g. digitoxigenin) and the addition of one or more sugar moieties at position C3modifies potency and duration of action, but not the fundamental pharmacological properties of this class of compound (Henderson, 1969).

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  1. Section of Cardiology, Pennsylvania Hospital, 8th and Spruce Streets, Philadelphia, USA

    Peter F. Binnion

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Binnion, P.F. Drug Interactions with Digitalis Glycosides. Drugs 15, 369–380 (1978). https://doi.org/10.2165/00003495-197815050-00003

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