PubMed · 5319524
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J L Dall. 1965. Digitalis intoxication.. https://doi.org/10.1016/0002-8703(65)90371-6
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Cardiac glycosides have played a prominent role in the therapy of congestive heart failure since William Withering codified their use in his late 18th century monograph on the efficacy of the leaves of the common foxglove plant (Digitalis purpurea). Despite their widespread acceptance into medical practice in the ensuing 200 years, both the efficacy and the safety of this class of drugs continue to be a topic of debate. Moreover, despite the fact that the molecular target for the cardiac glycosides, the alpha-subunit of sarcolemmal Na+K+-ATPase (or sodium pump) found on most eukaryotic cell membranes, has been known for several decades, it remains controversial whether the sympatholytic or positive inotropic effects of these agents is the mechanism most relevant to relief of heart failure symptoms in humans with systolic ventricular dysfunction. Herein, we review the molecular and clinical pharmacology of this venerable class of drugs, as well as the manifestations of digitalis toxicity and their treatment. We also review in some detail recent clinical trials designed to examine the efficacy of these drugs in heart failure, with a focus on the Digoxin Investigation Group data set. Although, in our opinion, the data on balance warrant the continued use of these drugs for the treatment of symptoms of heart failure in patients already receiving contemporary multidrug therapy for this disease, the use of digitalis preparations will inevitably decline with the maturation of newer pharmacotherapies.
Angiotensin-converting-enzyme inhibitors increase life expectancy in congestive heart failure, and they have thus changed the therapeutic strategy. The well tolerated highest daily dosage has to be used. Diuretics are often associated with vasodilators; however, they have to be administered at a minimal chronic daily dosage, in order to avoid deleterious neurohormonal effects. Digoxin keeps a great interest, as the unique positive inotropic agent without surmortality. Nitrates associated or not with hydralazine may show an additional interesting benefit. The role of other vasodilators, namely amlodipine and losartan, in the treatment of chronic heart failure remains to be defined. New vasodilators are in development and might further increase our therapeutic possibilities against congestive heart failure.
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