Sulfonamides
Sulfonamides (or sulfa drugs) are synthetic antimicrobial agents that interfere with bacterial folic acid synthesis. They are broad-spectrum and used against a wide range of bacteria and some protozoa.
Classification / Examples
- Co-trimoxazole = Sulfamethoxazole + Trimethoprim
- Sulfadiazine
Pharmacodynamics
- Sulfonamides are structural analogs of PABA (para-aminobenzoic acid).
- They competitively inhibit dihydropteroate synthase, blocking the formation of dihydropteroic acid (a folic acid precursor).
- This leads to reduced synthesis of tetrahydrofolic acid, impairing nucleic acid and protein synthesis in bacteria.
- Trimethoprim, given with sulfamethoxazole, inhibits dihydrofolate reductase, providing sequential blockade.
- Bacteriostatic, but can be bactericidal when combined (e.g., co-trimoxazole).
- Effective against:
- Gram-positive: Streptococcus pneumoniae
- Gram-negative: E. coli, H. influenzae
- Protozoa: Plasmodium spp., Toxoplasma gondii
- Nocardia, Pneumocystis jirovecii
Side Effects
- Common:
- GI upset: nausea, vomiting, diarrhea
- Hypersensitivity: rash, itching, fever
- Severe:
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Hematologic effects:
- Agranulocytosis
- Aplastic anemia
- Hemolytic anemia (especially in G6PD-deficient patients)
- Photosensitivity, crystalluria (due to low solubility)
Drug Interactions
- ↑ Effects of warfarin → ↑ bleeding risk
- ↑ Potentiation of oral hypoglycemics → risk of hypoglycemia
- ↑ Methotrexate toxicity (competes for albumin binding)
- ↑ Phenytoin levels → neurotoxicity
- ↑ Hematologic toxicity with bone marrow suppressants
- ↑ Nephrotoxicity with cyclosporine
- Caution with diuretics (e.g. thiazides, furosemide): ↑ risk of SJS/TEN