2-Sulfonamides

Protein binding 15 pharmacokinetics parameters of

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Unformatted text preview: 50 Sulfamethoxazole 11 70 25-30 80-100 Sulfadiazine 17 45 40-80 30-60 Sulfadoxine 100-230 80-98 20-30 50-75 When protein content is low, sulfonamides are present in unbound active form. Mandell, Table 34.1 Sunday, March 31, 2013 16 Sulfonamides Absorption / Fate / Excretion • Widely distributed Sulfadiazine • • • • Sunday, March 31, 2013 • Diffusable throughout total body H2O Sulfisoxazole • Confined to extacellular spaces Both may be effective in meningitis Cross the placenta → fetal circulation • What effects can be predicted in fetus? • • Antibacterial effects Toxic effects 17 Sulfonamides Metabolism and Elimination • • Liver • (free N group) Major derivative: N4-acetylated sulfonamide • • No ABX activity But, retains toxic potential of the parent substance Elimination • • • Sunday, March 31, 2013 In urine • t½ ≈ depends on renal function When urine is acid? • Insoluble agents → crystalluria In acidic urine, sulfonamides crystallize out, so now you have to alkalinize it Feces, bile, milk, other secretions 18 Pharmacological proteries of individual sulfonamides • • • • Agents that are absorbed rapidly and excreted rapidly • • • Sulfisoxazole (GANTRISIN), t½ ≈ 5-6 hrs Sulfadiazine, t½ ≈ 10 hrs Sulfamethoxazole, t½ ≈ 11 hrs Absorbed poorly • Sulfalazine • Active in the bowel Topical agents • • • Sulfacetamide • Sulfadoxine, t½ ≈ 100-230 hrs Mafenide Silver Sulfadiazine (SILVADENE) Long-acting agents -treats malaria Sunday, March 31, 2013 19 Sulfonamides Antimicrobial activity -by themselves have less utility than when combined • Inhibit • • • • Sunday, March 31, 2013 Gram-positive and Gram-negative bacteria Nocardia Chlamydia trachomatis Some enteric bacteria • • • • E coli Resistance has developed to Meningococci Streptococci Staphylococci Gonococci Klebsiella Salmonella Shigella 20 Therapeutic Uses of Sulfonamides • UTI • • Toxoplasmosis • Prophylaxis Nocardiosis • Sunday, March 31, 2013 Streptococcal infections • In patients hypersensitive to penicilins 21 Adverse reactions to sulfonamides • • • Urinary tract • Crystalluria • • • patients must drink lots of water with drug Less so with soluble agents • Sulfisoxazole Volume-depleted patients (e.g., AIDS) What would be the effect of urinary alkalinization? Hematopoietic system • • • Anemia Agranulocytosis Netropenia/ pancytopenia Rare Hypersensitivity reactions Sunday, March 31, 2013 • • • Generally rare and appear later in use. May appear quite early if patient has been previously sensitized. Role of pharmacist? 22 Drug Interactions with sulfonamides • • • Oral anti-coagulants Sulfonyl ureas Phenytoin The sulfonamides can potentiate the effects of these drugs. How? They inhibit the metabolism of CYP450 enzymes Sunday, March 31, 2013 23 • • • • SMX/TMP = 20/1 BACTRIM SEPTRA “An important advance in development of clinically effective a...
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