Sulfonamides(1)

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  • Considerable resistance has emerged
  • Trimethoprim is 20-100X as potent as the sulfonamide.
  • Unlikely in normal patients in recommended doses.
  • Sulfonamides(1)

    1. 1. SULFONAMIDES Recognized since 1932. In clinical usage since 1935. First compounds found to be effective antibacterial agents in safe dose ranges. Mainstay of therapy before penicillins.
    2. 2. SULFONAMIDES Now largely superceded by antibiotics and trimethoprim-sulfamethoxazole. They continue to occupy a small place in therapy.
    3. 3. Gram-negative Wheel of Bugs Neissseria spp H. influenzae E. Coli (coliforms) Bacteroides spp AnaerobicP. aeruginosa Clostridium spp S. aureus Enterococcus spp Streptococcus spp Gram-positive
    4. 4. FOLIC ACID BIOSYNTHESIS DIHYDROPTERIDINE 2 ATP PYROPHOSPHATE DERIVATIVEDihydropteroate 2HN COOHSynthetase HN SO2NH2 DIHYDROPTEROIC ACID 2 Glutamic Acid DIHYDROFOLIC ACID
    5. 5. BLOOD Protein Bound Kidney MetabolitesOral Other-Sweat, Free Saliva,X Topical Prostatic fluid,Parenteral Stool Body Fluids & Tissues CSF
    6. 6. KERNICTERUS IN THE NEWBORN Displacement of bilirubin from plasma protein binding sites.
    7. 7. METABOLISM O H3 HC C N SO2N RAcetylated sulfonamides-inactive, toxic,and less soluble
    8. 8. EXCRETION They are excreted in the urine partly as the parent and partly as the metabolite. Some sulfonamides are very insoluble in the acid urine.
    9. 9. EXCRETION Half life of the sulfonamides depends on renal function. Dosage should be modified or the sulfonamides should not be used in renal failure.
    10. 10. SULFONAMIDE PREPARATIONS Rapidly absorbed and rapidly eliminated (prototype- sulfisoxazole). Poorly absorbed sulfonamides (sulfasalazine). Topical sulfonamides (sulfacetamide, silver sulfadiazine). Long-acting sulfonamides (sulfadoxine)
    11. 11. CONTRAINDICATIONS
    12. 12. DRUG-DRUG INTERACTIONS Inhibit metabolism of some drugs. Displace certain drugs from plasma albumin.
    13. 13. TRIMETHOPRIM-SULFAMETHOXAZOLE OCH3 2 HN CH OCH3 2 OCH3 80 mg TRIMETHOPRIM 2 HN SO2NH N CH3 O 400 mg SULFAMETHOXAZOLE
    14. 14. COTRIMOXAZOLE Optimal ratio of the two drugs is 5:1 sulfa :trimethoprim.
    15. 15. Synergism
    16. 16. ADVANTAGES Expanded number of organisms inhibited. Bactericidal . Decreased resistance. Decreased toxicity.
    17. 17. THERAPEUTIC USES
    18. 18. hcd2.bupa.co.uk/.../ html
    19. 19. PNEUMOCYSTIS PNEUMONIA(PCP)
    20. 20. PNEUMOCYSTIS PNEUMONIA(PCP) www.learningradiology.com/
    21. 21. PNEUMOCYSTIS PNEUMONIA (PCP) The most common opportunistic infection in advanced AIDS (80% of AIDS patients have at least one episode). Now considered a fungus (P.jurovecii). Multiple infections are often present simultaneously with the PCP.
    22. 22. PROPHYLAXIS Routine prophylaxis has been successful in improving survival. PCP prophylaxis is indicated if the patient has a CD4 T lymphocyte count lower than 200 cells/mm3, or has oral candidiasis regardless of the CD4 count.
    23. 23. TREATMENT OF PCP Early therapy is essential as success of therapy is related to severity of the disease at the time of initiation of therapy.
    24. 24. TMP-SMX Treatment of choice. Oral form used for mild-moderate cases or after initial response to IV therapy and for prophylaxis.
    25. 25. TMP-SMX Excellent tissue penetration. Produces a rapid clinical response.
    26. 26. DRUG INTERACTIONS Same as with sulfonamides
    27. 27. other sulphonamides Sulphonylureas (anti-diabetic agents) Carbutamide Acetohexamide Chlorpropamide Tolbutamide Tolazamide Glipizide Gliclazide Glibenclamide (glyburide) Glibornuride Gliquidone Glisoxepide Glyclopyramide Glimepiride
    28. 28.  Anticonvulsants Acetazolamide Ethoxzolamide Sultiame Zonisamide Dermatologicals Mafenide
    29. 29.  Other Celecoxib (COX-2 inhibitor) Darunavir (Protease Inhibitor) Fosamprenavir (Protease Inhibitor) Tipranavir (Protease Inhibitor) Probenecid (PBN) Sotalol (Beta-blocker) Sulfasalazine (SSZ) Sumatriptan (SMT)
    30. 30.  Diuretics Acetazolamide Bumetanide Chlorthalidone Clopamide Dorzolamide Furosemide Hydrochlorothiazide (HCT, HCTZ, HZT) Indapamide Mefruside Metolazone Xipamide
    31. 31. Viable organisms 6 control 4 sulfonamide 2 0 1 2 3 4 5 6 7 8 9 Time of incubation (hrs)
    32. 32. RESISTANCE Results from multiple mechansims. Altered dihydropteroate synthetase. Cross-resistance among all sulfonamides.
    33. 33. PABA + PteridineDihydropteroate SULFONAMIDESynthetase DIHYDROPTEROIC ACIDDihydrofolate Synthetase DIHYROFOLIC ACID Dihydrofolate Reductase TRIMETHOPRIM TETRAHYDROFOLIC ACID
    34. 34. ADVERSE EFFECTS Hypersensitivity reactions -common  allergic rashes  photosensitivity  drug fever  Stevens-Johnson syndrome
    35. 35.  hypersensitivity reaction to sulfa drugs are rash and hives. However, there are several life-threatening manifestations of hypersensitivity to sulfa drugs, including Stevens–Johnson syndrome, toxic epidermal necrolysis, agranulocytosis, hemolytic anemia, thrombocytopenia, and fulminant hepatic necrosis, among others.
    36. 36.
    37. 37. CRYSTALLINEAGGREGATES,HEMATURIA,OBSTRUCTION
    38. 38. ADVERSE EFFECTS Headache, nausea, vomiting and diarrhea. Hematological effects -anemia, agranulocytosis.
    39. 39. ADVERSE REACTIONS Dermatological reactions including skin rashes. GI (nausea and vomiting).

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