Pharmacology Exam 1

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Author:
Rx2013
ID:
61161
Filename:
Pharmacology Exam 1
Updated:
2011-01-21 18:17:00
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Sulfonamides Quinolones
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Sulfonamides and Quinolones
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  1. synthesis of thymidine by dividing cells is supported by
    folic acid
  2. Thymidine is
    a precursor to DNA
  3. Bacteria synthesize folic acid from
    p-aminobenzoic acid (PABA)
  4. Do not make folic acid and must injest it
    vertebrates
  5. Inhibitors of folic acid synthesis
    • sulfonamides
    • target bacteria
  6. Synthesis of folic acid
    • Pteridine+Paba (Dihydropteroate synthase)
    • Dihydropteroic acid + glutamate (dihydrofolic acid synthatase)
    • Dihydrofolic acid + NADPH (Dihydrofolate reductase)
  7. Sulfanilamide
    • poor solubility and absorption
    • first sulfonamide
  8. More polar sulfonamides
    • sulfamethoxazole
    • sulfisoxazole
  9. Sulfadiazine
    • absorbed orally
    • low solubility
    • metabolized by CYP2C9
    • more soluble in alkalinized urine
  10. Sulfisoxazole
    • more solube than sulfadiazine in urine
    • excreted unchanged
    • used for UTIs
  11. Mafenide (Sulfamylon)
    topical use only
  12. Sulfasalazine (Axulfidine)
    • Prodrug
    • poor oral absorption
    • active drug is sulfapyridine
    • used for intestinal infections
  13. Trimethoprim
    • DHFR inhibitor
    • 5000x more selective for bacteria
  14. Trimethoprim/sulfamethoxazole
    • combo block of folate metabolism
    • synergistic effect
    • MIC is 1/4 the MIC for each drug alone
  15. Calculate the FIC for Trimethoprim/sulfamethoxazole
    FIC = 0.25/1 +0.25/1 = 0.5
  16. Methotrexate
    • binds tightly to DHFR from all sources
    • drawn to cancer cells because of high demand for nucleic acids
  17. Resistance to methotrexate is due to
    elevated levels of DHFR in resistant cells
  18. Methotrexate is used in
    • rheumatoid arthritis
    • psoriasis
  19. Adverse effects of sulfonamides
    crystalization in urine causes renal damage
  20. mechanisms to reduce crystals in urin from sulfonamides
    • increase urine volume
    • alkalinize urine with NaBicarb
  21. Effects of sulfonamides on blood
    • acute hemolytic anemia
    • aplastic anemia
    • agranulocytosis
  22. GI effects of sulfonamides
    • Anorexia
    • vomiting
  23. Sulfonamide effects on hair folicles
    alopecia
  24. Target of quinolones
    DNA Gyrase (topoisomerase II)
  25. Mechanism of action of quinolones
    block DNA gyrase which blocks tension release in replicating DNA
  26. Selectivity of quinolones
    gram negative bacteria
  27. Action of topoisomerase II
    change topology from a positive supercoil to a negative supercoil
  28. Naldixic acid
    • early quinolone
    • used only for lower UTIs
  29. Fluoroquinolones
    • Cipro, ofloxacin
    • much more effective than naldixic acid
    • better absorption and solubility
  30. Half life of quinolones
    • 3-10 hours
    • once a day dosing
  31. quinolones inhibit
    • CYP1A2
    • CYP2C9
    • CYP3A4
  32. Quinolones inhibit metabolism of
    • warfarin
    • theophylline
    • NSAIDS
    • Herbal & food supplements
  33. Quercetin from food and herbal products
    inhibits quinolones by biding DNA gyrase
  34. Quinolones are not used in children due to
    joint inflammation

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