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Introduction
  • Classification
    • antibiotic
      • miscellaneous
        • sulfonamides ("sulfa drugs")
  • Drugs
    • sulfamethoxazole (SMX)
    • sulfisoxazole
    • sulfadiazine
Mechanism
  • Action
    • bacteriostatic
    • recall that tetrahydrofolate (THF or TH4) is used to synthesize DNA
    • humans get THF from our diet, but bacteria make their own THF
    • sulfonamides inhibit dihydropteroate synthetase, a key enzyme in the bacterial THF synthesis pathway, thereby inhibiting the formation of bacterial DNA
      • sulfonamides look like PABA, an early input into the pathway
      • bacteria mistake sulfonamides for PABA, and the sulfonamides thereby act as a competitive inhibitor against dihydropteroate synthetase
  • Synergy with trimethoprim (TMP)
    • TMP acts via the same pathway, but inhibits a different enzyme further downstream
  • Resistance
    • resistance is common and is achieved via
      • ↓ intracellular accumulation of drugs
      • ↑ production of PABA by bacteria
      • ↓ sensitivity of dihydropteroate synthetase to sulfonamides
    • may be plasmid-mediated
Uses
  • Used in combination with TMP (as TMP-SMX -- "Bactrim") to treat the following
  • Respiratory
    • Strep pneumoniae
    • H. influenzae
    • Nocardia
    • Chlamydia
  • GI
    • E. coli
    • Salmonella
    • Shigella
  • GU
    • UTIs or prostatitis
      • also used for UTI prophylaxis
    • Chlamydia
  • AIDS
    • Pneumocystis jiroveci pneumonia (PCP)
      • also used for PCP prophylaxis
    • Toxoplasma gondii
      • use sulfadiazine
Adverse effects
  • Allergy
    • sulfa drug allergies are common
    • the following drugs are also contraindicated in patients with sulfa drug allergies
      • sulfasalazine
      • sulfonylureas
      • thiazide diuretics
      • acetazolamide
      • furosemide
  • Drug interactions
    • raises serum levels of warfarin by displacing it from albumin
  • Nephrotoxicity
    • tubulointerstitial nephritis
  • Hemolysis
    • in G6PD deficiency
  • Photosensitivity
  • Avoid in pregnancy
    • kernicterus in infants
Pharmacology
  • Solubility
    • "triple sulfa" therapy uses a combination of 3 sulfonamides to prevent precipitation of these relatively insoluble drugs
    • weakly acidic; lower solubility in acidic urine
 

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