Term
| What are structural characteristics of fluoroquinolones? |
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Definition
(Derived from parent quinolone, nalidixic acid)
Two fused six-membered rings with nitrogen; know that the fluoride increases potency (vs. quinolones)
[image]
Note: Quinolones (no fluoride) have good Gram- activity and no aminoglycoside-like toxicity, but it is easy to develop resistance against them. |
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Term
| What are common fluoroquinolones? |
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Definition
Cipro-, levo-, gemifloxacin
Note: Cipro exhibits post-antibiotic effect has particularly good penetration of bronchil/lung tissue, and is a good choice for respiratory infections.
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Term
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Definition
Binds DNA coiling enzymes, inducing double-stranded DNA breaks.
DNA gyrase (primary target in Gram-) and topoisomerase IV (primary target in Gram+) relax positive supercoils in replicating DNA. Quinolones bind to these enzymes and inhibit re-ligation after the double-stranded nick. |
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Term
| Are quinolones bacteriostatic or bactericidal? |
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Definition
Bactericidal. (Double-stranded DNA breaks always kill cell.) |
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Term
| What are mechanisms of resistance to quinolones? |
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Definition
1. Efflux: Upregulation of pre-existing transporters that use H+ motor force to pump out drug.
Note: In Gram= bacteria, pumps can efflux many drugs. In Gram+ organisms, pumps are selective for fluoroquinolones.
2. Mutation of topoisomerases prevents quinolone binding.
Note: Mutation in a single topoisomerase (DNA gyrase or topoisomerase IV) will confer intermediate-level resistance; mutation in both is needed for high-level resistance. |
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Term
| How are fluoroquinolones administered and distributed? |
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Definition
Good oral bioavilability (70%).
Note: Di- and trivalent cations decrease absorption (don't take with milk/antacid)
Wide distribution to most tissues and body fluids; variable CSF penetration. |
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Term
| How are fluoroquinolones metabolized and excreted? |
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Definition
Predominantly cleared renally, though some are metabolized in liver and cleared through bile. |
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Term
| What are targets of fluoroquinolones? |
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Definition
Classic target is Gram-, but also some activity against Gram+ (E. coli UTI), atypticals/intracellular (e.g. C. pneumoniae). Poor activity against anaerobes. |
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Term
| What are clinical uses of fluroquinolones? |
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Definition
1. UTIs (E. coli, S. saprophyticus).
2. Respiratory infections (H. influenezae, M. pneumoniae)
Note: Very good penetration of bronchial mucosa and lung
3. Bacterial diarrheas
4. Osteomyelitis: penetrates bone. |
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Term
| What are adverse effects of fluoroquinolones? |
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Definition
Relatively safe, but some GI irritation and CNS effects (headache, dizziness), photosensitivity.
Unique to fluororquinolones:
Tendinitis, which can lead to tendon rupture (usually achilles)
Damages growing cartilage
Note: Contraindicated in children
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Term
| Who may not take quinolones? |
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Definition
Children;and pregnant women quinolones can damage growing cartilage.
Note: Not absolutely contraindicated if there are no alternatives. |
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