DISCUSSION OF RESULTS. 93 



Equally interesting is the observation of the writer, that in. the 

 guinea pig the difference in the toxicity between the subcutaneous 

 and intraperitoneal injections is very slight, while in the cat the 

 toxicity of cailVin is the same whether given by mouth or injected 

 into the subcutaneous tissues, and is markedly less when injected into 

 the peritoneal cavity. The experiments on dogs show considerable 

 variation of effective dose when given by mouth, but the interest- 

 ing observation was made that the toxic dose by mouth may be 

 smaller in some cases than the average dose by subcutaneous injec- 

 tion. If the resistance to caffein by subcutaneous injection of the 

 different species of animals experimented upon in the present research 

 be compared, it will be noticed that the gray rabbit or Belgian hare, 

 wliich is more resistant than the other varieties employed, stands 

 more caffein in proportion to the weight of the body than the other 

 animals. 



Although the minimum fatal dose was found to be somewhat larger 

 for the guinea pig than for the gray rabbit when caffein was injected 

 intraperitoneally, it was on the contrary smaller by other paths of 

 hit reduction, and approximated quite closely the minimum fatal 

 dose for rabbits of the other varieties. Cats as well as dogs were 

 found to be distinctly less resistant to caffein than the herbivora. 



There are a number of factors far more important than zoological 

 differences which influence the toxicity of caffein. Some of these 

 are age, season, and pathologic conditions. As these factors have 

 already been dwelt upon in their appropriate places, further discus- 

 sion mignt seem unnecessary, but owing to their importance in deter- 

 mining the action of a'drug, emphasis is desirable. Especially is this 

 the case with pathological conditions hi relation to toxicity. While 

 no positive proof of diminished resistance to caffein in pathological 

 conditions was obtained by subjecting the suggestion to experimental 

 test, it was observed hi these experiments on rabbits that death 

 occurred in some individuals after small doses which are usually not 

 even toxic. The findings at autopsy indicate the presence of patho- 

 logical conditions. The same was observed in some experiments on 

 cats and dogs. It is extremely probable, therefore, that disease 

 modifies the reaction of the organism to- caffein as well as to other 

 drugs.* 8 



That the resistance to drugs may vary according to the age of the 

 subject has been maintained by a number of pharmacologists. Accord- 

 ing to Guinard, 30 young dogs, rabbits, and guinea pigs are very sus- 

 ceptible to morphin, resembling children in this regard. The mini- 

 mum fatal dose for these animals is about one-third less than for the 



a A case of accidental poisoning reported recently by Wlchura (Munich, Med. Woch., 1911, No. 30, p. 

 1618) throws some doubt on the accepted view that the susceptibility of young children to morphin is 

 greater than that of adults. Wichura also found that the therapeutic doses ol codein preparations ordi- 

 narily recommended for children in pleuritic cough are not effective In this condition. 



