Sulfonamides (Antibacterial agents) : Examples, Mechanism of Action and Adverse Effects

Sulfonamides History and Chemical Nature:

Sulfonamides belong to a class of antibacterial agents used for treating the bacterial infections. The first sulfonamide is sulfanilamide which is a metabolic product obtained from the inactive prodrug named prontosil dye.Sulfonamide is the active metabolite and treats bacterial infections. Many sulfonamides are discovered later, of which some of them have become resistant.

Antibacterial agents – Sulfonamides

Examples of some sulfonamides are sulfadiazine, sulfadimidine (short acting sulfonamide), sulfamethoxazole (intermediate acting), sulfametopyrazine (long acting), sulfasalazine. Sulfamethoxazole and trimethoprim are given together named as cotrimoxazle.

Mechanism of action:

Sulfanilamide is a structural analogue of para-aminobenzoicacid (PABA). PABA is an essential precursor for the syntesis of folic acid which inturn synthesizes the precursors of nucleic acids like DNA and RNA in both bacteria and also mammals. Bacteria has to synthesise the folic acid by using PABA in the presence of the enzyme dihydropteroate synthetase, where as mammals obtain the folic acid from the dietary. There comes the physiological difference between the bacteria and mammals and the action of sulfonamides comes here.

Sulfonamides act by interfering with PABA for the enzyme dihydropteroate synthetase and prevents the synthesis of folic acid thereby preventing the formation of nucleic acids in the bacteria. The action of sulfonamides can be altered by adding excess of PABA. Local anaesthetics are mainly PABA esters and when these are administered the antibacterial activity of sulfonamides gets reduced. Sulfonamides act mainly by inhibiting the growth of bacteria (bacteriostatic) and does not kill them bactericidal). Sulfonamides activity will be less when pus is present as the pus contains some purines and thymidine, so bacteria bypasses the folic acid synthesis pathway and directly uses the purines from pus and synthesizes nucleic acids.

Adverse Effects of Sulfonamides:

Nausea and vomiting are general side effects when any antibiotic is administered. It should not be applied topically as it may cause allergic reactions. Main adverse effects include hepatitis, bone marrow depression, hypersensitivity reactions (fever, rashes), and crystalluria (crystalluria results due to matabolites of sulonamides which are acetylated derivatives, in the urine).