Drug Reactions, Enzymes, and Biochemical Genetics

In discussions of drug idiosyncrasy, careful distinction should be made between toxic reactions caused by immunologic mechanisms (drug allergy) and abnormal reaction caused by exaggeration or diminution of the usual effect of a given dose. 1 Although some progress has been made in the study of mechanisms of drug allergy, little was known until recently about the pathogenesis of hypersusceptibility reactions and hyposusceptibility reactions. Data are available now which suggest that reactions of this type may be caused by otherwise innocuous genetic traits or enzyme deficiencies. Hockwald and his co-workers 2 demonstrated that approximately 10% of American Negroes and a very small number of caucasians developed hemolytic anemia when given an average dose of primaquine or chemically related drugs. Beutler and associates 3 showed that red blood cells of susceptible individuals possessed decreased numbers of nonprotein, sulfhydryl groups. It has now been pointed out that primaquine sensitivity is related to