M1EDICAL PRO6RESS: Sulfonamide Toxicity

APPROXIMATELY ten years have passed since the introduction of the sulfonamides into clinical medicine, and during this decade tremendous strides have been made in the control of infection by chemotherapy with various members of this group of drugs and the antibiotics. At present the major interest of both the lay and professional mind in this regard is centered on the antibiotics, but there is little doubt that the sulfonamides will continue to play an important part in the treatment of bacterial infections. Therapeutic efficacy plus ease of administration and relatively low cost makes these drugs very valuable agents indeed. The serious disadvantage of the sulfonamides is the toxic reaction which occasionally occurs during use of them. And since considerable time has elapsed since their introduction, this review is undertaken in order to present an overall evaluation of these toxic manifestations. Such an effort seems justified by the fact that a comprehensive, up-to-date analysis of the problems of sulfonamide toxicity is not available. Spink,74 Van Dyke,80 and Beckman6 have written at considerable -length on the subject; but these articles are somewhat outdated by new developments, and the last rather minimizes the hypersensitive type of renal and myocardial lesion. This situation is in contrast with the large volume of writing dealing with various individual aspects of sulfonamide toxicity: over 400 papers have appeared since 1941 in the English language alone. These articles for the most part deal with isolated phases of the subject pertaining to one drug, to one specialty, or one experimnental project, and nowhere is there a complete discussion of the whole problem. The present paper has been limited to developments since 1941 and to drugs which are now in clinical use: sulfathiazole, sulfadiazine, sulfamerazine, sulfacetamide, sulfasuxidine, and sulfathalidine. No space is devoted to a resume of the history of chemotherapy, to listing priority in reporting of the various toxic reactions, or to the results of animal experimentation unless these seem particularly pertinent. No effort has been made to compile the total numbers of the various reported reactions, and the statistical approach is used as -little as possible. The mere fact that a certain severe and possibly fatal reaction to a sulfonamide does occur should place th,e practitioner on his guard,; lhe should not be lulled into a sense of security by the statistical infrequency of that reaction. GENERAL CONSIDERATIONS