II. Mechanism
- Sulfonamide Antibiotics are natural or synthetic Sulfanilamide derivatives
- Sulfonamide Antibiotics are antimetabolites, agents that inhibit DNA, RNA and Protein synthesis via Tetrahydrofolate path blockade
- Sulfonamides are structural analogs of para-aminobenzoic acid (PABA) which is key to microbial Tetrahydrofolate synthesis
- Sulfonamides competitively inhibit PABA at the dihydropteroate synthase enzyme in production of Dihydropteric acid
- Dihydropteric acid is a Tetrahydrofolate precursor, and blocking its synthesis, blocks Bacterial DNA, RNA and Protein synthesis
- Trimethoprim also inhibits Bacterial Tetrahydrofolate synthesis (blocks dihydrofolate reductase at tetrahydofolic acid generation)
- Sulfonamides precipitate in the urine at therapeutic doses
- Limits Sulfonamides alone to subtherapeutic doses
- Combining Sulfonamides with other agents (e.g. trimethoprim) allows them to reach therapeutic levels without urine precipitation
III. Medications
-
Trimethoprim Sulfamethoxazole (Bactrim, Septra)
- Covers enteric Gram Negative Bacteria (Urinary Tract Infections) and some Gram Positive organisms
- Also used in PCP Pneumonia treatment and prophylaxis (AIDS) and MRSA Skin Infections
-
Sulfadiazine
- Broad spectrum activity against both Gram Positive and Gram Negative organisms
- Use limited to Toxoplasmosis Prevention and management (combined with Pyrimethamine and leucovorin)
- Silver Sulfadiazine Topical Cream (Silvadene, SSD) has a limited role in Burn Injury
- Sulfisoxazole (Gantrisin)
- Primarily indicated in Urinary Tract Infection prophylaxis
- Higher urine solubility than other Sulfonamides (lower precipitation risk)
IV. Contraindications
- Avoid in infant under age 2 months
- Sulfonamide Allergy
- G6PD Deficiency
V. Adverse Effects: General
- Allergic Reaction or Anaphylaxis
- Bone Marrow suppression (Agranulocytosis)
- Steven's Johnson Syndrome
- Toxic Epidermal Necrolysis
- Hepatotoxicity
- Hemolysis (in G6PD Deficiency)
-
Neonatal Hyperbilirubinemia and Kernicterus
- Sulfonamides compete with Bilirubin for albumin binding
- Results in increased free Bilirubin, with risk of Neonatal Hyperbilirubinemia and Kernicterus
VI. References
- Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 111