Fluoroquinolones

Drugs:

Ciprofloxacin, Norfloxacin, Enoxacin, Ofloxacin, Lomefloxacin, Levofloxacin, Trovafloxacin, Gatifloxacin, Moxifloxacin, Gemifloxacin.

Mechanism of action

Inhibition of DNA gyrase and topoisomerase IV, therefore directly inhibiting bacterial DNA synthesis (bactericidal).

Spectrum of activity

• Conventional bacteria

  • Fluoroquinolones have the greatest activity against aerobic gram-negative bacilli. They are also effective against Haemophilus spp, gram-negative cocci such as Neisseria spp and non-enteric gram-negative bacilli such as Pseudomonas aeruginosa and staphylococci

• Mycobacteria

  • Levofloxacin and Moxifloxacin have been shown to be active in vitro and in animal models of tuberculosis. Fluoroquinolones are active against M. fortuitum, M. kansasii, and some strains of M. chelonae but only fair or poor activity against M. avium complex.

• Other bacteria

  • Ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin and moxifloxacin have activity against agents of atypical pneumonias including Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.

Resistance

• During fluoroquinolone therapy, resistant organisms emerge with a frequency of about one in 107 – 109, especially among staphylococci, pseudomonas, and serratia.

• Resistance is due to one or more point mutations in the quinolone binding region of the target enzyme or to a change in the permeability of the organism.

• Fluoroquinolone resistant strains of Streptococcus pneumoniae are emerging with their increased use in the treatment of respiratory tract infections

Pharmokinetics

• Well absorbed from the upper gastrointestinal tract, with bioavailability of 80-95%.

• Peak concentrations in serum are usually attained within one to three hours of administering a dose.

• Food does not substantially reduce quinolone absorption but may delay the time to reach peak drug concentrations in serum

• Half lives range from three hours for norfloxacin and ciprofloxacin to six to eight hours for levofloxacin, gatifloxacin, moxifloxacin and gemifloxacin.

• Ofloxacin, levofloxacin and gatifloxacin are predominately eliminated by the kidneys. Most other quinolones have mixed excretion by both renal and nonrenal routes

Adverse reactions

They are extremely well tolerated. Reported adverse effects include:

• Adverse gastrointestinal symptoms are the most common side effects and include anorexia, nausea, vomiting, and abdominal discomfort.

• Symptoms of mild headache, dizziness, insomnia and mood alterations.

• Allergic and skin reactions have also occurred.

• Arthropathy and tendinopathy.

• QT prolongation

• Increase in transaminases

• Hypoglycemia and hyperglycemia

Drug interactions

• When co-administered by mouth with aluminium-, magnesium-, or calcium containing antacids, they have markedly reduced oral bioavailability.

• Concurrent administration with ferrous sulfate, multivitamins containing zinc have also been reported to reduce quinolone absorption

References

1. Appelbaum, P.C., and Hunter P.A., The fluoroquinolone antibacterials: past, present and future perspectives, International Journal of Antimicrobial Agents, 2000; 16: 5-15.

2. Basic and Clinical Pharmacology, 9th Edition, Katzung.

3. UptoDate: Fluoroquinolones

Category: Pharmacology Notes