MECHANISM OF ACTION & ANTIMICROBIAL ACTIVITY: Sulfonamide-susceptible organisms, unlike mammals, cannot use exogenous folate but must synthesize it from PABA. This pathway is thus essential for production of purines and nucleic acid synthesis. Nucleic acids As structural analogs of PABA, sulfonamides inhibit dihydropteroate synthase and thus folate production.
SPECTRUM OF ACTIVITY: Sulfonamides inhibit both gram-positive and gram-negative bacteria, Nocardia sp, Chlamydia trachomatis, and some protozoa. Some enteric bacteria, such as Escherichia coli, Klebsiella pneumoniae, Salmonella, Shigella, and Enterobacter sp are also inhibited. It is interesting to note however that rickettsiae are not inhibited by sulfonamides but are instead stimulated in their growth. The activity is poor against anaerobes. Pseudomonas aeruginosa is intrinsically resistant to sulfonamide antibiotics. Bacteriology: Antibiotics Combination of a sulfonamide with an inhibitor of dihydrofolate reductase (trimethoprim or pyrimethamine) provides synergistic activity because of sequential inhibition of folate synthesis.
RESISTANCE: Mammalian cells and some bacterial cells lack the enzymes required for folate synthesis from PABA and depend on exogenous sources of folate; therefore, they are not susceptible to sulfonamides. Sulfonamide resistance may occur as a result of mutations that; (1) cause overproduction of PABA, (2) cause production of a folic acid-synthesizing enzyme that has low affinity for sulfonamides, or (3) impaired permeability to the sulfonamide.
CLINICAL USES: Sulfonamides are infrequently used as single agents. Many strains of formerly susceptible species, including meningococci, pneumococci, streptococci, staphylococci, and gonococci, are now resistant. Antimicrobial drug resistance The fixed-drug combination of trimethoprim-sulfamethoxazole is the drug of choice for infections such as Pneumocystis jiroveci (formerly P. carinii) pneumonia, toxoplasmosis, nocardiosis, and occasionally other bacterial infections.
ORAL ABSORBABLE AGENTS: Sulfisoxazole and sulfamethoxazole are short- to medium-acting agents used almost exclusively to treat urinary tract infections. The usual adult dosage is 1 g of sulfisoxazole four times daily or 1 g of sulfamethoxazole two or three times daily. Sulfadiazine in combination with pyrimethamine is first-line therapy for treatment of acute toxoplasmosis. The combination of sulfadiazine with pyrimethamine, a potent inhibitor of dihydrofolate reductase, is synergistic because these drugs block sequential steps in the folate synthetic pathway blockade. The dosage of sulfadiazine is 1 g four times daily, with pyrimethamine given as a 75-mg loading dose followed by a 25-mg once-daily dose. Folinic acid, 10 mg orally each day, should also be administered to minimize bone marrow suppression. Sulfadoxine is the only long-acting sulfonamide currently available in many countries including sub Saharan Africa, and only as a combination formulation with pyrimethamine (Fansidar), a second-line agent in the treatment of malaria.
ORAL NONABSORBABLE AGENTS: Sulfasalazine (salicylazosulfapyridine) is widely used in ulcerative colitis, enteritis, and other inflammatory bowel disease.
TOPICAL AGENTS: Sodium sulfacetamide ophthalmic solution or ointment is effective in the treatment of bacterial conjunctivitis and as adjunctive therapy for trachoma. Another sulfonamide, mafenide acetate, is used topically but can be absorbed from burn sites. The drug and its primary metabolite inhibit carbonic anhydrase and can cause metabolic acidosis, a side effect that limits its usefulness. Silver sulfadiazine is a much less toxic topical sulfonamide and is preferred to mafenide for prevention of infection of burn wounds.
ADVERSE REACTIONS: All sulfonamides, including antimicrobial sulfas, diuretics, diazoxide, and the sulfonylurea hypoglycemic agents, have been considered to be partially cross-allergenic. The most common adverse effects are fever, skin rashes, exfoliative dermatitis, photosensitivity, urticaria, nausea, vomiting, diarrhea, and difficulties referable to the urinary tract. Other unwanted effects include stomatitis, conjunctivitis, arthritis, hematopoietic disturbances, hepatitis, and, rarely, polyarteritis nodosa and psychosis.
RELATED;
1. Artemisinin and its derivatives
2. Antibiotics
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