Information About

Fluoroquinolones
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The quinolones are a family of Broad-spectrum Antibiotics . The parent of the group is Nalidixic Acid . The majority of quinolones in clinical use belong to the subset of '''fluoroquinolones''', which have a fluoro group attached the central ring system, typically at the 6-position.


MECHANISM

Quinolones and fluoroquinolones are bactericidal drugs, actively killing bacteria. Quinolones inhibit the bacterial DNA Gyrase or the Topoisomerase IV enzyme, thereby inhibiting DNA replication and transcription. Quinolones can enter cells easily and therefore are often used to treat intracellular pathogens such as '' Legionella Pneumophila '' and '' Mycoplasma Pneumoniae ''. For many Gram-negative Bacteria DNA gyrase is the target, whereas topoisomerase IV is the target for many Gram-positive bacteria. Eukaryotic cells do not contain DNA gyrase or topoisomerase IV.


ADVERSE EFFECTS

Quinolone antibiotics were once considered relatively safe, but several Side Effect s have become evident with experience. For example, numerous case reports have implicated their use since 1965 in spontaneous Tendon ruptures or damage, especially with the concurrent use of a systemic Corticosteroid . In the fall of 2004, the Food And Drug Administration upgraded the warnings found within the package inserts for all drugs within this class regarding such serious adverse reactions. It is important to note, though, that the incidence of this is quite rare, with occurrences at less than one per ten thousand person-years.

  • Peripheral neuropathy (nerve damage): "Rare cases of sensory or sensor motor axonal polyneuropathy affecting small and or large axons resulting in paresthesias, hypoaesthesias, dysesthesias, and weakness have been reported in patients taking quinolones. Therapy should be discontinued if the patient experiences symptoms of neuropathy including pain, burning, tingling, numbness and or weakness or is found to have deficits in light touch, pain, temperature, position sense, vibratory sensation, and or motor strength in order to prevent the development of an irreversible condition."


  • Tendon damage: "Ruptures of the shoulder, hand, Achilles tendon or other tendons that require surgical repair or resulted in prolonged disability have been reported in patients receiving quinolones. Post-marketing surveillance reports indicate that this risk may be increased in patients receiving concomitant corticosteroids, especially the elderly. Fluoroquinolone therapy should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon. Patients should rest and refrain from exercise until diagnosis of Tendinitis or tendon rupture had been excluded. Tendon rupture can occur during or after therapy with quinolones.".


Other problems include:



RESISTANCE


Resistance to quinolones can develop rapidly, even during a course of treatment. Numerous Pathogen s, including '' Staphylococcus Aureus '', Enterococci , and '' Streptococcus Pyogenes '' now exhibit resistance worldwide.M Jacobs, Worldwide Overview of Antimicrobial Resistance. International Symposium on Antimicrobial Agents and Resistance 2005. Widespread veterinary usage of quinolones, particularly in Europe, has been implicated.


GENERATIONS

The quinolones are divided into generations based on their antibacterial spectrum. The earlier generation agents are generally more narrow spectrum than the later ones.


1st generation



2nd generation



3rd generation



4th generation



In development



VETERINARY USE

The quinolones have been widely used in agriculture and several agents exist which have veterinary but not human use.


EXTERNAL LINKS



REFERENCES