sulfonamidet

Sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group, -SO2NH-. They were among the first effective antibiotics, developed in the 1930s after observations that para-aminobenzoic acid (PABA) analogs could suppress bacterial growth. Their principal action is competitive inhibition of dihydropteroate synthase in the bacterial folate synthesis pathway, reducing production of dihydrofolic acid and thymidine needed for DNA synthesis. Humans obtain folate from diet, giving a therapeutic window that favors bacteria.

Chemistry and pharmacokinetics: Sulfonamides are generally weak acids; substitutions affect solubility and tissue distribution. Many forms exist as water-soluble salts for oral or parenteral use. They are absorbed well orally, distribute widely, and are excreted mainly by the kidneys. The duration of action varies by compound and renal function.

Medical use and examples: Historically used for urinary tract infections and skin infections. Topical sulfonamides, such as silver sulfadiazine or mafenide, are used for burns. Systemic combinations with trimethoprim (co-trimoxazole) exploit two-block signaling in folate synthesis and have broad activity against many bacteria and Pneumocystis jirovecii; sulfadiazine with pyrimethamine is used for toxoplasmosis in some regimens.

Safety and resistance: Adverse effects include allergies, rash, photosensitivity, crystalluria, and hematologic effects. Severe cutaneous adverse reactions can occur, and sulfonamides are generally avoided in late pregnancy and in newborns due to kernicterus risk. Resistance arises from DHPS mutations or increased PABA synthesis. Because of safety concerns and resistance, use has declined for some indications but remains important for selected infections and combinations.