Sulfonamides are synthetic bacteriostatic antibiotics that competitively inhibit conversion of p-aminobenzoic acid to dihydropteroate, which bacteria need for folate synthesis and ultimately purine and DNA synthesis. Humans do not synthesize folate but acquire it in their diet, so their DNA synthesis is less affected.
Sulfonamides include the following:
Three sulfonamides, sulfisoxazole, sulfamethizole, and sulfasalazine, are available as single drugs for oral use. Sulfamethoxazole is coformulated with trimethoprim (as TMP/SMX). Sulfadoxine combined with pyrimethamine is available for oral use.
Sulfonamides available for topical use include silver sulfadiazine and mafenide burn cream, sulfanilamide vaginal cream and suppositories, and sulfacetamide ophthalmic.
Sulfonamides are active against
Sulfasalazine can be used orally for inflammatory bowel disease.
Topical sulfonamides can be used to treat the following:
Evidence regarding an association between sulfonamides and birth defects is mixed. Animal studies with sulfonamides show some risk, and adequate studies have not been done in pregnant women.
Use near term and in breastfeeding mothers is contraindicated, as is use in patients < 2 months of age (except as adjunctive therapy with pyrimethamine to treat congenital toxoplasmosis). If used near term during pregnancy or in neonates, these drugs increase blood levels of unconjugated bilirubin and increase risk of kernicterus in the fetus or neonate.
Sulfonamides enter breast milk.
Adverse effects of sulfonamides can result from oral and sometimes topical sulfonamides; effects include
Hypersensitivity reactions, such as rashes, Stevens-Johnson syndrome, vasculitis, serum sickness, drug fever, anaphylaxis, and angioedema
Crystalluria, oliguria, and anuria
Hematologic reactions, such as agranulocytosis, thrombocytopenia, and, in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, hemolytic anemia
Kernicterus in neonates
Neurologic effects, such as insomnia, and headache
Hypothyroidism, hepatitis, and activation of quiescent systemic lupus erythematosus may occur in patients taking sulfonamides. These drugs can exacerbate porphyrias.
Incidence of adverse effects is different for the various sulfonamides, but cross-sensitivity is common.
Sulfasalazine can reduce intestinal absorption of folate (folic acid). Thus, use of this drug may trigger folate deficiency in patients with inflammatory bowel disease, which also reduces absorption, especially if dietary intake is also inadequate.
Mafenide may cause metabolic acidosis by inhibiting carbonic anhydrase.
To avoid crystalluria, clinicians should hydrate patients well (eg, to produce a urinary output of 1200 to 1500 mL/day). Sulfonamides can be used in patients with renal insufficiency, but peak plasma levels should be measured and sulfamethoxazole levels should not exceed 120 mcg/mL.
Sulfonamides can potentiate sulfonylureas (with consequent hypoglycemia), phenytoin (with increased adverse effects), and coumarin anticoagulants.