234 EXPERIMENTAL INVESTIGATION OF TilE ACTION OF MEDICINES. 



sufficiently large and frequent doses. The size of the dose and 

 the frequency with which it must be repeated in order to pro- 

 duce a cumulative effect w411 differ according to the rapidity 

 v^ith which the drug is excreted ; for, if excretion be rapid, a 

 larger dose, or more frequent repetition, will be required. The 

 long time which elapses before a dose of opium takes effect on 

 some individuals is probably due to its being very slowly 

 absorbed ; and the power of one man to take, without apparent 

 effect, an amount of alcohol or opium which would intoxicate 

 another, to its either being more slowly absorbed from the 

 stomach or intestine, or more quickly excreted by the lungs, 

 skin, or kidneys, so that the amount present in the blood at any 

 one time is never sufficient to produce toxic effects. There are 

 two vegetable active principles, digitalin and strychnia, to which 

 an especial cumulative action is ascribed. After moderate doses 

 of these drugs have been taken for some time, it is found that 

 instead of the effects they produce increasing gradually, as we 

 would expect from a gradual accumulation in the blood, the 

 symptoms of poisoning become suddenly developed in some- 

 what the same way as if the dose had been suddenly increased. 

 It is evident that a diminution in the quantity excreted will 

 produce this effect as readily as an increase in the quantity 

 taken, and this is probably the true cause of the phenomenon. 

 When digitalin has been taken for some time and accumulated 

 to a certain extent in the blood it causes a diminution in the 

 amount of urine excreted, and this diminution is either accom- 

 panied or quickly followed by the other symptoms of poison- 

 ing.* The effect indeed seems exactly the same as Hermann 

 would have obtained in his experiment if he had only partially 

 compressed the renal arteries instead of ligaturing them com- 

 pletely. For digitalin appears to diminish the secretion of urine 

 by exerting a powerful action on the renal vessels,t and in large 

 doses may completely arrest the secretion of urine,t and prob- 

 ably also the circulation through the kidneys. 



* Brunton, On Digitalis, toith some Observations on Urine, p. 39 {vide antea^ 

 p. 61). 



t Brunton and Power, Froc. Boy. Soe., 1874, jS^o, 153, and Centralhlatt d. 

 Med. Wiss., 1874, p. 497 {mde postea, pp. 410 and 412). 



X Cliristison, Edin. 3Ied. Journ., vol. vii, p. 149. Mazel, Gazette de* 

 Eo^itaux 1861-74. 



