THE INFLUENCE OF CERTAIN DRUGS UPON THE TOXICITY 
OF ACETANILIDE AND ANTIPYRINE.“" 
By Worth Hale, 
Assistant Pharmacologist, Division of Pharmacology, Hygienic Laboratory, Zf. S. Public 
Health and Marine- Hospital Service. 
Summary . — The results of the experiments which are recorded in 
this bulletin indicate that the deleterious effect of acetanilide upon 
the heart is very imperfectly antagonized by caffeine. They show 
that so far as the contractile power of the heart is concerned the 
antagonism is very weak or even not present at all, and in some 
cases that the two drugs seem to combine to depress the heart to a 
greater degree than acetanilide does xvhen given alone. The heart 
rate, on the other hand, is not slowed after a mixture of acetanilide 
and caffeine are gh^en, as is the case when acetanilide is given alone, 
and the decreased heart rate following the exhibition of the former 
alone tends to become normal upon the subsequent injection of 
caffeine. Caffeine is further shown to increase the toxicity of acet- 
anilide mixtures xvhen given to the intact animal, and in certain 
experiments this is not only a summation effect but even some 
synergistic action is to be observed. 
Sodium bicarbonate, quite in contrast, appears to markedly lessen 
the poisonous effects of acetanilide upon the heart, which is shown 
to be less depressed than xvhen the alkali is not given. The lessened 
toxicity also appears in the experiments upon the intact animal, in 
which case acetanilide when given alone proved to be far more toxic 
than in mixtures with the alkalies. 
The combinations of the alkaloids of the morphine group also 
increase the toxic effects of acetanilide, while mixtures containing 
salicylic acid and the bromides seem not to alter its poisonous effects 
in any Avay. 
“Submitted for publication April 29, 1909. 
&The experiments recorded in this bulletin were suggested by some preliminary 
experiments carried out by Doctor Hunt, in February, 1908, his results indicating 
that caffeine increased the toxicity of both acetanilide and antipyrine very materially. 
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