Evidence for pharmacodynamic differences between cardiac glycosides of different polarities
We compared the effects of digitoxin (lipophilic) and ouabain (hydrophilic) in rats under pentobarbital anaesthaesia on inotropy (dp/dt) and atrioventricular conduction (PR-interval). Doses of the glycosides which produced a 40–50% increase in dp/dt produced a significantly greater prolongation of the PR interval with ouabain than with digitoxin. Neither vagotomy nor atropine administration abolished this difference, but the difference could be eliminated by pre-treatment with propranolol. We concluded that the smaller effect of digitoxin on atrioventricular (AV) conduction was due to a central sympathomimetic effect which does not occur with ouabain.
A respiratory depressant effect of digitalis has been reported in humans. We therefore compared the effect of acetyldigitoxin (relatively lipophilic) to that of digoxin (relatively hydrophilic) on the hyper-ventilatory response to inhaled CO2 in healthy volunteers. We found that at mean steady state levels of 12.5 ± 1.07 ng/ml (digitoxin) and 0.87 ± 0.2 ng/ml (digoxin), digitoxin appeared to stimulate ventilation as measured by minute ventilation and oxygen consumption and digoxin appeared to depress ventilation. These observations appear to be consistent with a sympathomimetic effect of the acetyldigitoxin as observed in our animal experiments. It might also be consistent with a greater vagomimetic effect with digoxin as suggested by Runge in 1977. Further research is currently being done to elucidate the mechanisms of the observed differences.
These findings suggest that when cardiac glycosides are used for supraventricular tachyarrhythmias a more hydrophilic cardiac glycoside might be indicated. If on the other hand digitalis is used for its positive inotropic effect, the use of a lipophilic cardiac glycoside might reduce the risk of atrioventricular block. It also seems that if digitalis is used in patients with respiratory impairment, a more lipophilic cardiac glycoside might be preferable.
KeywordsAtrioventricular Block Ventilatory Response Cardiac Glycoside Positive Inotropic Effect Atrioventricular Conduction
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