title: Effects of pharmacologic alterations of adrenergic mechanisms by cocaine, tropolone, aminophylline, and ketamine on epinephrine-induced arrhythmias during halothane-nitrous oxide anesthesia.
abstract: The purpose of this study was to examine the effects of pharmacologic alterations of adrenergic terminating mechanisms by cocaine, tropolone, aminophylline, and ketamine on the ability of epinephrine to induce arrhythmias during halothane-nitrous oxide anesthesia in dogs. Because the first three drugs inhibit intraneuronal uptake of catecholamines, extraneuronal catechol-O-methyl transferase (COMT), and phosphodiesterase, respectively, they might be expected to potentiate epinephrine-induced arrhythmias. To evaluate this possibility, the authors devised a technique for determining the minimal arrhythmic dosage of epinephrine that permitted graded assessment of changes in the sensitivity of the heart to epinephrine-induced arrhythmias. When the first three drugs were administered to the same dog in the order listed at intervals of 60 minutes, they sequentially increased the ability of epinephrine to induce arrhythmias. Ketamine, according to several investigators, also appears to block reuptake of catecholamines, and when studied was also found to enhance the arrhythmogenicity of epinephrine. The extent of enhancement was comparable to that seen with cocaine. These results indicate that drugs like cocaine and ketamine that interfere with intraneuronal uptake can facilitate the development of epinephrine-induced arrhythmias and that the successive pharmacologic interference of intraneuron uptake, COMT, and phosphodiesterase leads to a stepwise increase in the arrhythmogenicity of epinephrine.
mesh_terms: D000628:Aminophylline / Q000494:pharmacology*; D000770:Anesthesia, Endotracheal; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D003508:Cycloheptanes / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006221:Halothane; D006339:Heart Rate / Q000187:drug effects; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013874:Thiopental / Q000008:administration & dosage; D014334:Tropolone / Q000494:pharmacology*
chemical_list: D003508:Cycloheptanes; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D000628:Aminophylline; D007649:Ketamine; D014334:Tropolone; D003042:Cocaine; D013874:Thiopental; D006221:Halothane; D004837:Epinephrine