Sulfonamides

Sulfonamides can be divided into three major groups: (1) oral, absorbable; (2) oral, nonabsorbable; and (3) topical. The oral, absorbable sulfonamides can be classified as short-, medium-, or long acting on the basis of their half-lives.

Mechanisms of action: Microorganisms require extracellular para-aminobenzoic acid (PABA) to form dihydrofolic acid, an essential step in the production of purines and the synthesis of nucleic acids. Sulfonamides are structural analogs of PABA that competitively inhibit dihydropteroate synthase. They inhibit growth by reversibly blocking folic acid synthesis.

Sulfonamides inhibit both gram-positive and gram-negative bacteria, Nocardia, Chlamydia trachomatis, and some protozoa. Some enteric bacteria, such as E coli, Klebsiella, Salmonella, Shigella, and Enterobacter, are inhibited.

Pharmacokinetics: They are absorbed from the stomach and small intestine and distributed widely to tissues and body fluids, placenta, and fetus. Absorbed sulfonamides become bound to serum proteins to an extent varying from 20% to over 90%. A portion of absorbed drug is acetylated or glucuronidated in the liver. Sulfonamides and inactivated metabolites are then excreted into the urine, mainly by glomerular filtration.

Clinical Uses

Oral Absorbable Agents: Sulfisoxazole and sulfamethoxazole are short- to medium-acting agents that are used to treat urinary tract infections, respiratory tract infections, sinusitis, bronchitis, pneumonia, otitis media, and dysentery. Sulfadiazine in combination with pyrimethamine is first-line therapy for treatment of acute toxoplasmosis. Sulfadoxine, long- acting sulfonamide, in combination with pyrimethamine used as a second-line agent in treatment for malaria.

Oral Nonabsorbable Agents: Sulfasalazine is widely used in ulcerative colitis, enteritis, and other inflammatory bowel disease. Sulfasalazine is split by intestinal microflora to yield sulfapyridine and 5-aminosalicylate. Salicylate released in the colon in high concentration is responsible for an antiinflammatory effect. Comparably high concentrations of salicylate cannot be achieved in the colon by oral intake of ordinary formulations of salicylates because of severe gastrointestinal toxicity.

Topical Agents: Sodium sulfacetamide ophthalmic solution or ointment is effective treatment for bacterial conjunctivitis and as adjunctive therapy for trachoma. Silver sulfadiazine is a much less toxic topical sulfonamide and is preferred to mafenide for prevention of infection of burn wounds.

Adverse Reactions: The most common adverse effects are fever, skin rashes, exfoliative dermatitis, photosensitivity, urticaria, nausea, vomiting, and diarrhea. Stevens-Johnson syndrome, crystalluria, hematuria, hemolytic or aplastic anemia, granulocytopenia, and thrombocytopenia occur less frequently. Sulfonamides taken near the end of pregnancy increase the risk of kernicterus in newborns.