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Fluoroquinolones

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Topic updated on 07/23/17 6:08am

Introduction
  • Classification
    • antibiotic
      • miscellaneous
        • fluoroquinolones
  • Drugs
    • 1st generation (quinolone)
      • nalidixic acid
    • 2nd generation
      • ciprofloxacin
      • norfloxacin
      • enoxacin
      • ofloxacin
      • levofloxacin
    • 3rd generation
      • gatifloxacin
    • 4th generation
      • moxifloxacin
      • gemifloxacin
Mechanism
  • Action
    • bactericidal
    • inhibits DNA gyrase (prokaryotic topoisomerase II)
      • DNA gyrase normally relieves strain while DNA is unwound by helicase
      • inhibition leads to breakage of bacterial DNA
      • humans do not have DNA gyrase
        • although we have another type of topoisomerase II
          • etoposide targets it in cancer chemotherapy
    • 4th generation also targets topoisomerase IV
  • Resistance
    • point mutation in DNA gyrase confers resistance to ALL the fluoroquinolones in one fell swoop
Uses
  • Gram-negative UTIs and GI tract infections
    • E. coli
    • Salmonella
    • Shigella
    • Campylobacter
  • Pseudomonas aeruginosa
    • especially in cystic fibrosis
  • Gram-positive coverage in 3rd and 4th generations
  • Anaerobic coverage in 4th generation
  • Neisseria
  • Bacillus anthracis
Adverse effects
  • Cation interaction
    • do not take with antacids
  • GI upset
  • Cartilage damage
    • avoid in pregnancy and in children
    • kids have more cartilage
  • Tendon rupture
    • especially Achilles tendon
    • especially ciprofloxacin
  • C. difficile colitis
  • CNS
    • headache
    • dizziness
    • restlessness, insomnia
  • Rashes
  • Myalgias in children
Pharmacology
  • High levels of drug in GI tract and in kidneys make it useful for treating GI tract infections and UTIs
    • enterohepatic circulation
      • excreted in bile and reabsorbed
    • excreted via kidneys
  • Oral absorption
  • Penetrates into tissues well
    • can be used to treat facultative intracellular organisms (e.g. Salmonella)


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