PHYSIOLOGICAL ACTIONS OF DRUGS ON THE SECRETION OF BILE. 153 
to be attributable to spasm of the larger bile ducts; therefore, an increase in 
secretion must have been the cause. 2. When the bile is prevented from 
entering the intestine, the podophyllin acts less powerfully and less quickly 
than when bile is introduced. 3. Augmentation of the biliary secretion is most 
marked when the purgative effect is not severe ; indeed, if the purgative effect 
be very decided (Experiment 9), diminution and not augmentation of the biliary 
secretion may be the chief result. 4. Podophyllin purgation is apparently due 
to a local action, for the irritation of the intestinal mucous membrane extends 
gradually from above downwards. It is a severe intestinal irritant. 5. The 
bile secreted under the influence of podophyllin, although it may be increased 
in quantity, contains as much of the special biliary matter as bile secreted under 
normal conditions. 
These results are in exact accordance with clinical experience of the action 
of podophyllin in man, but in addition they show that this substance actually 
increases the secretion of biliary matter, and that the liver is stimulated to 
secrete bile of the normal composition. They therefore supply information of 
a precise and important character, which the observations on the human subject 
have failed to give. 
In the experiments with podophyllin, performed by Hucures BEnNeETT’s 
committee above referred to, it was found that podophyllin diminishes the 
secretion of bile. How is that statement to be reconciled with the above ? 
The principal explanation is probably this, that in the experiments of the 
committee the doses given were large, and generally produced profuse purgation. 
We see that in Experiment 9 of this series diminished bile-secretion was the 
chief result of a dose that was too large, and it may be repeatedly observed in 
the following experiments :—1. That when a substance produces purgation, but 
does not stimulate the liver, it diminishes the secretion of bile. 2. That when 
a substance stimulates the liver as well as the intestinal glands, a moderate 
dose increases both the hepatic and the intestinal secretion, the effect on the 
former being most marked in the earlier part of the experiment, and diminishing 
as the purgative effect increases ; but an excessive dose, by producing a violent 
purgative effect early in the experiment, may occasion nothing but diminished 
secretion of bile. 
Speaking broadly—if in a fasting dog the administration of any substance 
cause the bile-secretion per hour, for every kilogramme of body-weight, to rise 
to 04 cc., the substance is to be regarded as a powerful hepatic stimulant. It 
will therefore be found of importance to compare the coefficients of secretion ob- 
tained after the administration of different substances. Necessarily, the results 
are only approximative, but are nevertheless of much value as furnishing for 
the first time the exact data necessary for a comparative estimate. Table IV. 
shows that in Experiment 10, the coefficient of secretion rose to the very high 
VOL, XXIX. PART I, 2R 
