SULFANILAMIDE

also spelled sulphanilamide, also called para-aminobenzenesulfonamide sulfonamide drug and the parent compound to which many other sulfonamide drugs are structurally related. Sulfanilamide is an important antimicrobial agent effective in treating infections caused by such bacteria as Streptococcus, Staphylococcus, Salmonella, and Coccidia. Although synthesized in 1908, sulfanilamide was only much later found to be the active metabolite, or therapeutically active breakdown product, of Prontosil (q.v.), the first sulfonamide drug used in medicine (early 1930s). Sulfanilamide itself was used orally and topically (as in the application to open wounds) beginning in the 1940s. Since the introduction of less toxic derivatives, however, it is now used only in veterinary medicine. Among other sulfonamide drugs derived from sulfanilamide are sulfadiazine, sulfamerazine, sulfamethazine, sulfathiazole, sulfisoxazole, and Sulfasuxidine. Sulfanilamide and its close relatives inhibit the growth of susceptible microorganisms by preventing the formation of folic acid, a member of the B-group of vitamins present in all living cells. Most bacteria make their own folic acid from simpler starting materials; humans and other higher animals, however, must obtain folic acid in the diet. Thus, these sulfonamides can inhibit the growth of invading microorganisms without harming the host. The first clue to the mode of action of the sulfonamides was provided in 1939, when a substance was discovered in yeast that antagonized the antibacterial effect of sulfanilamide; i.e., the substance suppressed the inhibition of the synthesis of folic acid in bacteria. In 1940 this substance was identified as para-aminobenzoic acid, which closely resembles sulfanilamide in structure. In fact, sulfonamides exert their antimicrobial effect by preventing the synthesis of folic acid by microorganisms by displacing para-aminobenzoic acid. Bacteria become increasingly resistant to the sulfonamides upon repeated exposure to them. These agents inhibit the growth and multiplication of bacteria; with the body's defense mechanism, they act to control infection. When the action of the sulfonamides is interfered with by pus or chemicals, such as procaine or para-aminobenzoic acid, strains of bacteria resistant to sulfonamide action emerge and survive. In an attempt to circumvent the low solubility and high toxicity of sulfonamides and to decrease their tendency to induce undesirable effects in hypersensitive persons, sulfonamide mixtures have been compounded. Highly soluble sulfonamidesmixtures that are more soluble than equivalent amounts of individual members of the mixtureare effective in the prevention and treatment of obstruction of the kidney that is caused by certain sulfonamides when used alone in large doses.