II. Mechanism

  1. Sulfonamide antibiotics are natural or synthetic Sulfanilamide derivatives
  2. Sulfonamide antibiotics are antimetabolites, agents that inhibit DNA, RNA and Protein synthesis via Tetrahydrofolate path blockade
    1. Sulfonamides are structural analogs of para-aminobenzoic acid (PABA) which is key to microbial Tetrahydrofolate synthesis
    2. Sulfonamides competitively inhibit PABA at the dihydropteroate synthase enzyme in production of Dihydropteric acid
    3. Dihydropteric acid is a Tetrahydrofolate precursor, and blocking its synthesis, blocks Bacterial DNA, RNA and Protein synthesis
    4. Trimethoprim also inhibits Bacterial Tetrahydrofolate synthesis (blocks dihydrofolate reductase at tetrahydofolic acid generation)
  3. Sulfonamides precipitate in the urine at therapeutic doses
    1. Limits Sulfonamides alone to subtherapeutic doses
    2. Combining Sulfonamides with other agents (e.g. trimethoprim) allows them to reach therapeutic levels without urine precipitation

III. Medications

  1. Trimethoprim Sulfamethoxazole (Bactrim, Septra)
    1. Covers enteric Gram Negative Bacteria (Urinary Tract Infections)
    2. Also used in PCP Pneumonia treatment and prophylaxis (AIDS) and MRSA Skin Infections
  2. Sulfadiazine
    1. Broad spectrum activity against both Gram Positive and Gram Negative organisms
    2. Use limited to Toxoplasmosis Prevention and management (combined with Pyrimethamine and leucovorin)
    3. Silver Sulfadiazine Topical Cream (Silvadene, SSD) has a limited role in Burn Injury
  3. Sulfisoxazole (Gantrisin)
    1. Primarily indicated in Urinary Tract Infection prophylaxis
    2. Higher urine solubility than other Sulfonamides (lower precipitation risk)

IV. Contraindications

  1. Avoid in infant under age 2 months
  2. Sulfonamide Allergy
  3. G6PD Deficiency

V. Adverse Effects: General

  1. Allergic Reaction or Anaphylaxis
    1. See Sulfonamide Allergy
  2. Bone Marrow suppression (Agranulocytosis)
  3. Steven's Johnson Syndrome
  4. Toxic Epidermal Necrolysis
  5. Hepatotoxicity
  6. Hemolysis (in G6PD Deficiency)
  7. Neonatal Hyperbilirubinemia and Kernicterus
    1. Sulfonamides compete with Bilirubin for albumin binding
    2. Results in increased free Bilirubin, with risk of Neonatal Hyperbilirubinemia and Kernicterus

VI. References

  1. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 111

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