Sulfonamides

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Sulfonamides

  1. 1. SULFONAMIDES AND COTRIMOXAZOLE
  2. 2. First antimicrobial agent effective against pyogenic bacterial infections They were developed from prontosil dye- Domagk (1937) Prontosil sulfanilamide All sulfonamides are derivatives of sulfanilamide(p-amino benzene sulfonamide)
  3. 3. <ul><li>Classification </li></ul><ul><li>Short acting (4-8hr) </li></ul><ul><li>Sulfadiazine,sulfadiamidine </li></ul><ul><li>2. Intermediate acting (8-12hr) </li></ul><ul><li>sulfamethoxazole,sulfamoxole </li></ul><ul><li>3. Long acting (7 days) </li></ul><ul><li>sulfadoxine,sulfamethopyrazine </li></ul><ul><li>4. Special purpose sulfonamides </li></ul><ul><li>sulfacetamide sod.,sulfasalazine, </li></ul><ul><li>mafenide,silver sulfadiazine </li></ul>
  4. 4. <ul><li>Classification according to therapeutic use </li></ul><ul><li>Topically applied sulfonamides </li></ul><ul><li>for eye infection- sulfacetamide(10%,20% & 30%) </li></ul><ul><li>for skin infection- silver sulfadiazine,mefanide acetate </li></ul><ul><li>GIT Infections </li></ul><ul><li>succinylsulfathaizole,phthalylsulfathiazole, </li></ul><ul><li>sulfaguanidine </li></ul><ul><li>Meningitis </li></ul><ul><li>sulfadiazine,sulfadimidine </li></ul><ul><li>UTI infections </li></ul><ul><li>sulfioxazole,sulfamethopyrazine </li></ul>
  5. 5. <ul><li>5 . Respiratory tract infections </li></ul><ul><li>sulfaphenazine,cotrimoxazole </li></ul><ul><li>Leprosy </li></ul><ul><li>dapsone,solapsone </li></ul><ul><li>7. Drugs for bowel disinfection </li></ul><ul><li>sulfasalazine,pthalylsulfathiazole </li></ul><ul><li>8 . Malaria </li></ul><ul><li>sulfadoxine+pyrimethamine </li></ul><ul><li>9. Nocardiosis </li></ul><ul><li>sulfadiazine,sulfisoxazole </li></ul>
  6. 6. BACTERIAL SPECTRUM Staphylococcus pneumonia S. Pyogenes H. Influenzae H. Ducrey Nocardia Actinomycin
  7. 7. Pteridine + PABA dihydropteroate synthetase Dihydroteroic acid glutamate Dihydrofollic acid dihydrofollate reductase Tetrahydrofollic acid sulfonamides (-) trimethoprim (-)
  8. 8. <ul><li>Resistance </li></ul><ul><li>Due to increased amount of PABA </li></ul><ul><li>If folate synthetase has low affinity for sulfonamides </li></ul><ul><li>alternate path for folate metabolism </li></ul><ul><li>Increased capacity to destroy drug </li></ul><ul><li>Gonococci,pneumococci,stapylococci,E.coli </li></ul>
  9. 9. PHARMACOKINETICS A- GIT D- plasma protein bound 10-95% M- N 4 acetylated sulfonamide E- urine,feaces,bile & milk
  10. 10. ADVERSE DRUG REACTIONS Crystalluria Nausea,vomiting kernicterus
  11. 11. COTRIMOXAZOLE sulfamethoxazole + trimethoprim (diaminopyrimidine) Trimethoprim is selective inhibitor of bacterial DHFR Individually they both are bacteriostatic but the combination is bacteroicidal
  12. 12. OPTIMAL SYNERGY sulfamethoxazole : trimethoprim 20 : 1 BBB & placenta- trimethoprim crosses both sulfamethoxazole does not PPB Trimethoprim- less 40% sulfamethoxazole- more 65% MIC trimethoprim- 3µg sulfamethoxazole-0.3µg Combination - Trimethoprim-1µg sulfamethoxazole-0.05µg
  13. 13. RESISTANCE decreases because resistance to one component may still be killed by other. Resistance to trimethoprim is mostly through mutational or plasmid mediated acquisition of DHFRase having lower affinity for the inhibitor. SPECTRUM Salmonella typhii Enterobacter Yersinia Pneumocystis carinii
  14. 14. PHARMACOKINETICS A- Trimethoprim is more rapidly absorbed peak blood concentration of T- 2hrs & S- 4hrs. D - V d of trimethoprim is 9 times that of sulfamethoxazole E - T- 60% excreted in 24 hrs S- 25-50% in 24 hrs
  15. 15. <ul><li>ADVERSE DRUG REACTIONS </li></ul><ul><li>Nausea, vomiting & headache </li></ul><ul><li>Folate deficiency </li></ul><ul><li>Blood dyscrasias </li></ul><ul><li>Patient with renal disease –uremia </li></ul><ul><li>In elderly-greater risk of bone marrow toxicity </li></ul>
  16. 16. USES UTI RTI Typhoid Chancroid Bacterial diarrhoeas & dysentery Granuloma inguinale Pneumocystis carinii

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