Sulfonamides

Mechanism of Action

  • Certain microbes require p-aminobenzoic acid (PABA) in order to synthesize dihydrofolic acid which is required to produce purines and ultimately nucleic acids.

  • Sulfonamides,chemical analogs of PABA, are competitive inhibitors of dihydropteroate synthetase.

  •  Sulfonamides therefore are reversible inhibitors of folic acid synthesis and bacterostatic not bacteriocidal.

 

Overview: Spectrum of Antimicrobial Activity and Resistance

  • Sulfonamides inhibit (bacteriostatic) gram-positive and gram-negative bacteria, Nocardia, Chlamydia trachomatis and some protozoa.

  • Enteric bacteria inhibited: E. coli, Klebsiella, Salmonella, Shigella and Enterobacter.

  •  Resistance to sulfonamides may develop when bacterial mutations result:

    •  in PABA overproduction

    •  in a folic acid synthesizing enzyme protein that has low affinity for sulfonamides

    •  from a loss of cell permeability to sulfonamides.

Pharmacokinetics

  •  Sulfonamides can be classified in three groups: oral, absorbable oral, nonabsorbable topical.

  •  Oral, absorbable agents may be further classified as short-, medium, or long acting.

  •  Sulfonamides are absorbed from the stomach and small intestine and widely distributed to tissues, including the CNS.

  •  Sulfonamides and inactivated metabolites are excreted by the kidney mainly through glomerular filtration.

 

Clinical Uses

  • Sulfonamides are useful in treating urinary tract infections, but in general are rarely used as single agents.

  • The fixed drug combination of trimethoprim-sulfamethoxazole (Bactrim) has supplanted many previous sulfonamide clinical uses.

  • Examples: sulfisoxazole (Gantrisin) and sulfamethoxazole (Gantanol) are used almost exclusive to treat UTI.

  • In combination with phenazopyridine, a urinary tract anesthetic, sulfonamides are available as Azo Gantrisin and Azo Gantanol.

  • sulfadiazine in combination with pyrimethamine (Daraprim) (antiprotozoal agent, dihydrofolate reductase inhibitor) is first-line treatment for acute toxoplasmosis.

  • cefpodoxime (Vantin), a long-acting sulfonamide, is used in combination with pyrimethamine as a second-line option for treating malaria.

  • Oral, Non-absorbable drugs: Sulfasalazine (Azulfidine) (salicylazosulfapyridine) is used in treating ulcerative colitis, enteritis and other inflammatory bowel disorders. The antiinflammatory action is due to the release of salicylate following splitting of sulfasalazine by intestinal bacteria.

  • Topical Agents: Bacterial conjunctivitis may be treated with sodium sulfacetamide opthalmic solution/ointment. Sodium sulfacetamide is an adjunctive drug in treating trachoma. Mafenide acetate is used in preventing infection in burn wounds.

 Adverse reactions

  •  most common: fever, rash, exoliative dermatitis, photosensitivity, urticaria nausea vomiting diarrhea urinary tract problems following precipitation of drug in urine.

  •  Sulfonamides may cause Stevens-Johnson syndrome (<1% frequency).

  •  Hemopoietic disturbances, including hemolytic or aplastic anemia, granulcytopenia, thrombocytopenia may be caused by sufonamides.

Chambers, H.F. and Jawetz, E.Sulfonamides,Trimethoprim, and Quinolones,in Basic and Clinical Pharmacology,(Katzung, B. G., ed) Appleton-Lange, 1998, p. 761-763.

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