Sulfonamides

• Sulphonamides were the first effective AMAs used in the treatment of bacterial infections in humans.
• Sulphonamides are derivatives of sulphanilamide (para-aminobenzene sulphonamide) and are synthetic compounds.
• Sulphonamides can be classified as systemic-acting agents and local-acting agents.
• Examples of local-acting sulphonamides include Sulphacetamide and Silver sulphadiazine.
• Examples of sulphonamides include Sulphasalazine, which acts both locally and systemically, and Sulphamethoxazole which is intermediate-acting (8-12h).
• Sulphadoxin is a long-acting sulphonamide (>7 days).
• Sulphadoxine is another long-acting sulphonamide.
• The mechanism of action of sulphonamides is that para-Aminobenzoic acid (PABA) is a precursor of folic acid which is essential for growth and multiplication of many bacteria.
• Sulphonamides, being structurally similar to PABA, compete with folate synthase enzyme and prevent the formation of folic acid, producing a bacteriostatic effect.
• Sulphonamides are not effective in the presence of pus as it is rich in PABA, purines and thymidine.
• Mammalian Cells do not synthesize folic acid but utilize folic acid present in diet hence are unaffected by sulphonamides.
• Most bacteria have developed resistance to sulphonamides due to decreased affinity of folate synthetase for the drug, efflux of the drug by bacteria, and development of alternate metabolic pathway for folate synthesis.
• All systemic-acting sulphonamides are well absorbed from the gut, bound to plasma proteins, particularly albumin, distributed in almost all tissues of the body including CSE, cross placental barrier and reach fetal circulation, metabolized in liver mainly by acetylation, and excreted partly unchanged and partly as metabolic products.
• The acetylated products of sulphonamides are poorly soluble in acidic urine and may cause crystalluria, haematuria or even obstruction to urinary tract.
• Hypersensitivity reactions to sulphonamides include skin rashes, itching, drug fever and exfoliative dermatitis, with Stevens-Johnson syndrome being the most severe type.
• In patients with glucose-6-phosphate dehydrogenase deficiency, sulphonamides may cause acute haemolytic anaemia.
• Rarely cause hepatitis and suppression of bone marrow.
• Use of sulphonamides in neonates, especially in premature babies, may cause displacement of bilirubin from plasma proteins, leading to kernicterus.
• Sulphonamides potentiate the effect of phenytoin, methotrexate (MTX), oral anticoagulants and oral hypoglycaemic agents (sulfonylureas) by inhibiting their metabolism and displacing them from plasma protein binding sites.
• Sulphonamides alone are rarely used now for systemic infections, used in combination with other AMAs.
• Sulphadoxine and pyrimethamine are used in combination with artesunate in the treatment of chloroquine-resistant Plasmodium falciparum malaria.
• Sulphadiazine and pyrimethamine combination is the drug of choice for toxoplasmosis.
• Nocardiosis: Sulphamethoxazole in combination with trimethoprim is used.
• Sodium salt of sulphacetamide is used exclusively for the treatment of ophthalmic infections, administered as eye drops or eye ointment, due to its high aqueous solubility, neutral pH and nonirritant nature, good penetrability on topical administration, low incidence of hypersensitivity reactions, and low cost.
• Silver sulfadiazine and mafenide are used topically for preventing infection of burn wound, with silver sulfadiazine slowly releasing silver ions which are toxic to microorganisms.
• Sulphasalazine is useful in the treatment of inflammatory bowel disease and rheumatoid arthritis.
• Rheumatic fever: Sulphadiazine can be used for prophylaxis of rheumatic fever.