PHYSIOLOGY, PHARMACOLOGY, AND TOXICOLOGY 387 



the doses involved have never exceeded 100 mg or so, and were generally 

 less (5-10 mg) . They were generally intravenous. These levels are far 

 below the lethal dose that might be anticipated from toxicity data in 

 lower animals. Unfortunately, however, little accurate toxicity data 

 exist for lower animals, and much of the data mentioned earlier is subject 

 to extreme question as regards its accuracy. The symptoms described in 

 acute cases involve those classically associated with anaphylaxis, 63-67 

 and in some cases at least hypersensitivity has been demonstrated by 

 passive transfer. 68 In sensitive persons, subcutaneous injection of small 

 amounts of thiamine generally causes large wheals, 68 although the validity 

 of such a skin test has been challenged. 69 Other symptoms often asso- 

 ciated with thiamine toxicity include herpes zoster, 70 - 71 headache, trem- 

 bling, and a rapid pulse. The symptoms have been likened to those 

 occurring from an overdose of thyroid extract, 72 and in general bear little 

 resemblance to the curare-like action seen in lower animals. 73-82 Attempts 

 to sensitize rabbits, dogs, and guinea pigs to thiamine have been unsuc- 

 cessful. 83 



Thiamine toxicity is a major problem from the practical standpoint 

 because large doses of thiamine are so frequently administered. It is for 

 this reason as much as any that a large number of toxic effects have been 

 reported for this B vitamin and not for the others. It seems quite clear 

 that the effects observed in man have little or no relationship to those 

 seen in lower animals — that in man the result is an allergic one in prob- 

 ably every case reported. 84, 85 That similar results occur from a large 

 variety of other popular pharmaceuticals — the sulfa drugs are a classic 

 example — would indicate that such an effect might well be anticipated. 

 Some workers have strongly advocated the complete abandonment of high 

 thiamine therapy, particularly by intravenous administration, for this 

 reason. In any case, it is readily apparent that two things are badly 

 needed at present: a thorough evaluation of individual responses to 

 thiamine, and accurate data on the toxicity levels of thiamine for lower 

 animals other than the mouse. Such information should certainly precede 

 any acceleration in the present trends toward massive vitamin therapy. 



Nicotinic Acid. Nicotinic acid and its amide like many pyridine 

 derivatives, have marked pharmacological activity. One of the most 

 important manifestations of this in man is the nitroid reaction, which is 

 similar to the effects of histamine and caused by nicotinic acid but not 

 the amide. 86-92 Shortly after a suitable dose of nicotinic acid is adminis- 

 tered, there is a marked flushing of the face, neck, and arms. The reaction 

 is due to a transient vasodilation which lasts for an hour or so and may 

 be accompanied by itching or burning. This flushing action is said to be 

 prevented by a previous oral dose of 30-60 gm of glycine. 93 There is an 



