EFFECTS OF CERTAIN DRUGS AND POISONS 771 



In Hanzlik's demonstration of salicyl anuria one sees a further reason 

 why the hyperglycemia tends to keep the volume of the blood high. 



Hirschfeld maintains that antipyretics relieve diabetes insipidus and 

 Gaulier finds that salicylates diminish the excretion of chlorids. These 

 and various other observations tend to support the belief that salicylates 

 induce oliguria. 



In Hanzlik's non-febrile cases the hemoglobin remained constant. 

 Barbour has found the hemoglobin percentage diminished in fever patients 

 during the antipyretic action of both acetyl-salicylic acid and antipyrin. 



The role of the excess sugar in producing hydremia is illustrated in 

 Barbour and Howard's results with dextrose in normal and fever dogs. 

 Intravenous dextrose injections, which in normal animals produce a slight 

 blood dilution with 110 temperature change, will dilute the blood two or 

 three times more extensively in fever animals coincidently with a marked 

 antipyretic action. These effects are short-lived when much sugar is used. 

 The sugar runs off in the urine presently and may leave the blood more 

 concentrated and the temperature higher than ever. 



Theory of the Mechanism of Fever Reduction by Drugs. All antipy- 

 retics act by increasing the heat elimination ; reduction in heat production 

 is incidental. Antipyretics increase the blood sugar concentration. In 

 fever extra water being available in the tissues, these drugs produce 

 plethora ; factors other than hyperglycemia may contribute to this result. 

 Plethora promotes the dissipation of heat by radiation and surface 

 evaporation. (Sweating is not essential to antipyretic action which pro- 

 ceeds unabated in the presence of atropin antidiaphoresis.) In health 

 no plethora occurs, consequently there is no antipyretic effect. 



The earlier work on the relation of "heat centers" to antipyretic action 

 is well presented by Gottlieb in Meyer and Gottlieb's pharmacological 

 treatise. 



Barbour and Wing have showed that local applications of antipyrin, 

 chloral or quinin to the heat centers in rabbits all gave better antipyretic 

 effects than the same doses by the intravenous or subcutaneous routes. 



Hashimoto later found that the antipyretic action of both antipyrin 

 and salicylate is enhanced by heating the centers but annulled by cooling. 

 After quinin only heat was found effective, cold having no effect. The 

 effects of heat and cold were prevented by morphin, as indeed the present 

 author has often noticed to be true of ether. 



Vasomotor effects figure largely in these "heat center" reactions which 

 it is expected can be correlated ultimately with the blood dilution theory. 



Acid-Alkali Metabolism. Meyer found no change in the alkalinity 

 of the blood with salicylates. In fatal poisoning, however, Walter found 

 a low carbon dioxid content. Acetonuria is reported by Langmead and 

 by Lees from large doses of salicylates, and in children. Piccini found 

 that phenacetin and acetanilid, and, to a lesser extent, antipyrin, reduced 



