A STUDY OF THE BRONCHOCONSTRICTOR AND HYPOTENSIVE ACTIONS OF CURARIZING DRUGS

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Abstract
In unanesthetized spinal dogs, artificial respiration through a tracheal can-nula was maintained by a Drinker-Murphy infant resuscitator adapted to record bronchial caliber by the plethysmographic method of Jackson. Intocostrin, d-tubocurarine chloride, curarine chloride, and quinine methochloride, when administered intraven. in curarizing dosage, caused broncho-constriction and hypotension. Quinine methochloride was the least potent in these respects. Dihydro-beta-erythroidine hydrobromide, except for its slight hypotensive effect, failed to produce these responses even though it was a satisfactory curarizing agent. Peptone, when administered intraven., produced peptone shock characterized by bronchoconstriction and hypotension. This was similar to but usually more severe than curare "shock." The prophylactic admn. of an antihistamine agent, pyribenzamine hydrochloride, inhibited the bronchoconstrictor response to curare but had little if any inhibitory effect on the hypotensive response; it inhibited the responses to peptone similarly but less completely. The inhibitory effect of cyribenzamine on curare "shock" was confirmed with another antihistamine agent, benadryl. In evoking bronchoconstriction and hypotension, curare prepns. and peptone solns. not only produced a "dose-to-dose refractoriness" to themselves, but also produced varying degrees of crossed "desensitization" against one another. There occurred a certain incidence of spontaneous refractoriness to each. The results obtained in this study substantiate the theory that curare prepns. and peptone solns. administered intraven. elicit bronchoconstriction and hypotension through the liberation of histamine from the body tissues. This study suggests that it may prove possible to avoid the complicating bronchoconstrictor and to a lesser extent the hypotensive action of curare either by employing curarizing drugs which, as was the case with dihydro-beta-erythroidine in spinal dogs, do not have bronchoconstrictor or severe hypotensive actions, or by prophylactically administering an antihistamine drug, such as pyribenzamine or benadryl, before the intraven. injn. of a curare prepn. The most rational treatment of these side reactions would appear to be the prompt admn. of an antihistamine drug.