FLUROQUINOLONES

  • Be able to understand the different groups of fluroquinolones.
Structure/Class
  1. Fluorinated analogs of nalidixic acid.
Pharmacodynamics
  1. Functions by blocking DNA gyrase and topoisomerase IV.
    • This prevents normal DNA transcription and replication.
  2. Note that fluroquinolones were developed to have good Gram+ve and Gram-ve cover. They can be divided into three groups based on activity
    • Group 1 – norfloxacin. It is the least active of all fluroquinolones against Gram-ve and Gram+ve bacteria.
    • Group 2 – ciprofloxacin, which has excellent Gram-ve cover and moderate to good Gram+ve cover.
      1. Effective against Enterobacter, Neisseria, Pseudomonas, Campylobacter and Haemophilus.
      2. In particular, ciprofloxacin has the most effective Gram-ve cover.
      3. It is effective against MSSA but not MRSA.
      4. It has limited efficacy against strep and enterococcus.
    • Group 3 – moxifloxacin, which has excellent Gram-ve cover and good Gram+ve cover, having activity against staph and strep.
  3. Overall, fluroquinolones do have coverage against atypical pneumonia agents (Chlamydia, legionella and mycoplasma) and against mycobacterium.
    • Hence, indications are as follows:
      1. UTI – because all fluroquinolones (except moxi) achieve good levels in urine.
      2. Bacterial diarrhea (salmonella, shigella)
      3. Intra-abdominal infections
      4. Respiratory infections
      5. May be used to treat chlamydial infections.
  4. Note that high level resistance to one fluroquinolone will generally confer resistance to all other members of this class. Resistance is due to:
    • Alteration in quinolone binding region
    • Alteration in permeability of the drug
    • May be plasmid related
Absorption/administration
  1. PO – bioavailability of >95%. Note that absorption is impaired by divalent cations (same property as tetracyclines) and therefore should not be taken together with antacids.
Distribution  
Metabolism
  1. Most fluroquinolones are renally cleared, either by glomerular filtration or tubular secretion. Dose reduction is needed in renal failure.
  2. Moxifloxacin is the exception – it is hepatically metabolized, and dose should be reduced in hepatic failure (not renal failure)
Excretion  
Adverse events
  1. GIT effects – nausea, vomiting and diarrhea
  2. CVS – may cause long QTc. Avoid fluroquinolones if patient is already on QT-prolonging drugs.
  3. Cartilage damage and arthropathy – avoid prescribing in <18 years old.
  4. Tendonitis/tendon rupture
Dosing/administration  
Toxicology  
Withdrawal syndrome  
Special notes