Increase in the cardiotonic action and in the therapeutic margin of digoxin by the adrenergic beta-stimulant doxaminol in cats.
The interaction between digoxin and the beta-sympathomimetic drug doxaminol was investigated in cats with acute heart failure induced by pentobarbital sodium. Doxaminol, 50 micrograms/kg X min, infused for 60 min caused a dose-dependent rise in dp/dtmax with little increase in heart rate. The maximum increase of 4.3 mHg/s was obtained after about 37 min. Digoxin, 10 micrograms/kg X min, and the combination of both drugs were infused until cardiac arrest. The maximum increase of dp/dtmax was observed after 29 min in both experiments; it was 5.7 mHg/s with digoxin alone and 7.3 mHg/s with the combination (p = 0.025). The combined infusion of epinephrine (0.3 micrograms/kg X min) plus digoxin (10 micrograms/kg X min) caused a maximal increase of dp/dtmax by 7.9 mHg/s. The cardiotoxic dose of digoxin was markedly reduced by epinephrine, not by doxaminol. The relevance of this difference to man cannot be assessed definitely because the ECG changes produced by digoxin in cats are different from those seen in man.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002415:Cats; D003990:Dibenzoxepins / Q000494:pharmacology*; D004077:Digoxin / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D002316:Cardiotonic Agents; D003990:Dibenzoxepins; D011943:Receptors, Adrenergic, beta; C034187:doxaminol; D004077:Digoxin; D010424:Pentobarbital