Digitalis Glycosides: A Discussion of the Similarities and Differences in Actions and Existing Controversies

Abstract

The writing of this review was initiated to answer the question of whether differences in the actions of the various digitalis glycosides exist and to discuss current controversies in the research area of the digitalis glycosides. Data obtained in our laboratory /1,2/ indicated that the effect of digoxin on postganglionic cardiac sympathetic neural discharge in the minute prior to the occurrence of arrhythmia differed from that of ouabain. This raised the question of whether data published in other laboratories would support the contention that differences in glycosides do exist. To answer this question, a review of the literature was begun. Our survey of these studies are cited in the tables of this review. These tables summarize the actions of glycosides in vivo and in vitro in different animal models. The reader should bear in mind that the data included within the tables do not represent an inclusive summary of all studies in the literature. For detailed review articles, the reader is referred to the following references: Gillis et al /3/; Gillis and Quest /4/; Roberts et al /5/; Lathers and Roberts /6/; Farah and Alousi /7/; Benthe /8/; Levitt et al /9/; Smith and Haber /10/; Somberg /ll/; Lee and Klaus /12/; Mason /13/; Schwartz /14·/. Furthermore the summary of the results for each particular study cited in the table may not, in all cases, include each finding of the published data. Nevertheless, the tables do provide a summary of data obtained in various species with different glycosides in several different areas of research, and as such, represent an abridged compendium for the researcher working in the field of digitalis glycosides. This review has been organized firstly to consider glycoside-induced alterations in the autonomic nervous system and, secondly, to examine their direct actions on the heart. Introduction Autonomic Nervous System A. Peripheral Sites The effect of digitalis glycosides on pre-and postganglionic cardiac sympathetic and parasympathetic nervesThe concept of a neural component in the pharmacology of digitalis glycosides is more than a century old /15,16/. The possibility of a peripheral but still nerve related site of action for digitalis glycosides was recognized butcontrol 20 40 60 80 100 control 20 40 60 80 100 % of Arrhythmoganic Dot· DIGITOXIN Spinal, Vagotomized I70r DIGOXIN Spinal, Vofotomizttf Fig. 2: The effect of digitoxin (left panels) or digoxin infusion* (right panels) on heert rate of animals with spinal cords transected with (lower panels) and without (upper panels) bilateral vagotomy. Upper Panel -Each point represents the average response of 9 animals. The vertical bars indicate standard errors. Lower Panel -Each point represents the average response of 8 animals. The vertical bars indicate standard errors. Modified from Pace et el., Eur J Pharmacol 1974; 28: 2881221. a. Quinidine When considering the action of glycosides, one question which should be asked is whether the ability of all digitalis glycosides to produce cardiac 8 Brought to you by | New York Univers...

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“…19 Explanations for these differences were explored in two in-depth reviews of studies conducted in multiple species with various digitalis glycosides. 20,21 These data suggested that differences existed between the two digitalis glycosides, ouabain and digoxin, in that the nonuniform effect on the peripheral sympathetic neural discharge played a greater role in ouabain-induced arrhythmias.…”