Sulfonamides

Most sulfonamides are readily absorbed orally and, when applied to burns, topically. Sulfonamides are distributed throughout the body. They are metabolized mainly by the liver and excreted by the kidneys. Sulfonamides compete for bilirubin-binding sites on albumin.

Sulfonamides are active against

• A broad spectrum of gram-positive and many gram-negative bacteria

• Plasmodium and Toxoplasma species

Sulfasalazine can be used orally forinflammatory bowel disease.

Sulfonamides are most commonly used with other antibiotics (eg, for nocardiosis, urinary tract infection, and chloroquine-resistant falciparum malaria).

Topical sulfonamides can be used to treat the following:

• Burns: Silver sulfadiazine and mafenide acetate

• Vaginitis: Vaginal cream and suppositories with sulfanilamide

• Superficial ocular infections: Ophthalmic sulfacetamide

Sulfonamides are contraindicated in patients who have had an allergic reaction to them or who have porphyria.

Sulfonamides do not eradicate group A streptococci in patients with pharyngitis and should not be used to treat group A streptococcal pharyngitis.

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 medications increase blood levels of unconjugated bilirubin and increase risk ofkernicterus 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

• Photosensitivity

• Neurologic effects, such as insomnia, and headache

Hypothyroidism, hepatitis, and activation of quiescent systemic lupus erythematosus may occur in patients taking sulfonamides. These medications can exacerbate porphyrias.

Incidence of adverse effects is different for the various sulfonamides, but cross-sensitivity is common.

Sulfasalazine can reduce intestinal absorption offolate(folic acid). Thus, use of this medication may triggerfolate 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.