FLOROQUINOLONES

INTRODUCTION: Although the first drug in this class, nalidixic acid, was approved by the FDA in 1962, it had a narrow spectrum of activity, and its use was restricted to UTIs. Nalidixic acid is still used for the pharmacotherapy of UTI, although it is not a preferred drug for this infection. Since then, four generations of fluoroquinolones have become available, differing in their antibacterial spectrums. All fluoroquinolones have activity against gram-negative pathogens; the newer ones are significantly more effective against gram-positive microbes, such as staphylococci, streptococci, and enterococci. Enterobacteriaceae

SPECTRUM OF ACTIVITY: The fluoroquinolones are bacteriocidal and affect DNA synthesis by inhibiting two bacterial enzymes: DNA gyrase and topoisomerase IV.

CLINICAL APPLICATIONS: Clinical applications of fluoroquinolones include infections of the respiratory, GI, and genitourinary tracts, and some skin and soft-tissue infections. Their effectiveness against gram-negative organisms makes them preferred drugs for the treatment of uncomplicated UTIs. A newer drug in this class, moxifloxacin (Avelox), is effective against anaerobes, a group of bacteria that are often difficult to treat. The most widely used fluoroquinolone, ciprofloxacin (Cipro), is a drug of choice for the postexposure prophylaxis of Bacillus anthracis, the organism responsible for causing anthrax. Bacillus spp

Ciprofloxacin is also indicated for postexposure prophylaxis to other potential biologic warfare pathogens such as Yersinia pestis (plague), Francisella tularensis (tularemia), and Brucella melitensis (brucellosis). Two drugs in this class, gatifloxacin and besifloxacin, are available only as drops to treat infections of the external eye.

PHARMACOKINETICS: A major advantage of the fluoroquinolones is that most are well absorbed orally and may be administered either once or twice a day. Although they may be taken with food, they should not be taken concurrently with multivitamins or mineral supplements because calcium, magnesium, iron, or zinc ions can reduce the absorption of some fluoroquinolones by as much as 90%. Fluoroquinolones are well tolerated by most patients, with nausea, vomiting, and diarrhea being the most common adverse effects. The most serious adverse effects are dysrhythmias (moxifloxacin) and potential hepatotoxicity.

CNS effects such as dizziness, headache, and sleep disturbances affect 1% to 8% of patients. Most recently, fluoroquinolones have been associated with cartilage toxicity with an increased risk of tendonitis and tendon rupture, particularly of the Achilles tendon. The risk of tendon rupture is increased in patients over age 60 and those receiving concurrent corticosteroids. Because animal studies have suggested that fluoroquinolones affect cartilage development, these drugs are not approved for children under age 18. Use in pregnancy or in lactating patients should be avoided.

RELATED;

1.  DRUG USE AND PREGNANCY  

2.  SALFONAMIDES

3.  PHARMACOLOGY AND THERAPEUTICS

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