PHYSIOLOGY AND BIOCHEMISTRY OF SHOCK 411 



d. The Function of Antihistamine Substances and Their Phar- 

 macological Action. The release of histamine during anaphylaxis 

 would naturally produce symptoms which would, in certain respects, 

 be common to both anaphylactic and histamine shock. This is further 

 emphasized by the fact that the drugs which counteract or prevent 

 the action of histamine are also effective in anaphylaxis. Experimen- 

 tally, an antihistamine substance inhibits the physiological action of 

 histamine on the isolated intestine and uterus of animals, on the 

 bronchi, on the vessels; it protects the animal against lethal histamine 

 shock. The only action it does not suppress is the excito-secretory 

 power of histamine on the gastric, pancreatic and salivary secretions. 

 Used therapeutically, the antihistamines have already given remark- 

 able results in several allergic states, mainly serum sickness, some 

 urticaria, hay fever, etc. (Halpern, 1945; Mayer, 1947; Loew, 1947). 

 The prophylactic administration of Antergan (2339 RP) has been 

 found (Halpern, 1945) to be sufficient to avert completely anaphylactic 

 shock: blood pressure hardly changes, the usual hemoconcentration 

 is absent; dyspnea, algidity, hypothermia and sphincteral troubles are 

 likewise absent. This striking protective action is not permanent. After 

 a delay of about 5 days, these animals are again sensitive. It is then 

 possible to produce just as severe an anaphylactic shock in them as one 

 produces in the test animals. 



The antihistaminic drugs do not prevent the release of, or destroy 

 the released histamine. They prevent histamine from exercising its 

 action on the sensitive sites. The manner by which the antihistamines 

 bring about this effect is still unknown. Gruhzit and Fisken (1946) 

 found that benadryl and A-446 administered orally, intravenously, 

 subcutaneously and intraperitoneally were toxic in albino mice and 

 rats, rabbits and dogs. Both substances caused a complex syndrome of 

 excitement reactions predominantly neurogenic in origin involving 

 motor, sensory and automatic nervous systems. Barbiturates controlled 

 excitant neurologic reactions, but did not prevent respiratory-cardiac 

 depression. Irrespective of the mode of administration, toxic doses of 

 either compound caused excitement, spastic ataxia, extreme irritability, 

 sensitivity to sound, mydriasis which is due to a disorder of the central 

 nervous system, painful hyperesthesia, convulsive attacks, and respira- 

 tory and myocardial embarassment. Death occurred from respiratory 



