Sulfonamides

ByBrian J. Werth, PharmD, University of Washington School of Pharmacy
Reviewed/Revised May 2024
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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:

  • Sulfadoxine

  • Sulfamethizole

  • Sulfamethoxazole

  • Sulfisoxazole

Three sulfonamides, sulfisoxazole, sulfamethizole, and sulfasalazineTMP/SMX

Resistance

Sulfonamide resistance is widespread, and resistance to one sulfonamide indicates resistance to all.

Pharmacokinetics of 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.

Indications for Sulfonamides

Sulfonamides are active against

inflammatory bowel disease.

Sulfonamides are most commonly used with other antibiotics (eg, for nocardiosis, urinary tract infection, and ).

Topical sulfonamides can be used to treat the following:

Contraindications to Sulfonamides

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.

Use of Sulfonamides During Pregnancy and Breastfeeding

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 <kernicterus in the fetus or neonate.

Sulfonamides enter breast milk.

Adverse Effects of Sulfonamides

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.

folatefolate deficiency in patients with inflammatory bowel disease, which also reduces absorption, especially if dietary intake is also inadequate.

Dosing Considerations for Sulfonamides

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.

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