C.14. Quinolones and fluoroquinolones Flashcards
what are fluoroquinolones?
direct inhibitors of nucleic acid synthesis
what is the mechanism of action of fluoroquinolones?
- they interfere with bacterial DNA synthesis: inhibition of topoisomerase II in gram - and topoisomerase IV in gram +
- bactericidal effect
- exert post-antibiotic effect (PAE)
pharmacokinetic properties of fluoroquinolones
orally active
renal excretion (blocked by probenecid)
T1/2 3-8 hours
what you shouldn’t mix with fluoroquinolones?
coffee and theophylline (↑ concentration)
Ca²⁺, Mg²⁺ and Fe ²⁺ (alters the oral activity of fluoroquinolones)
what is the mechanism of resistance of fluoroquinolones?
- efflux pump, changes in porin structure (gram -)–> ↓ intracellular accumulation of the drug
- changes in the sensitivity of target enzymes via point mutation
how many generations of fluoroquinolones are there?
4
1st generation–> quinolone
1-3 aerobes
4 anaerobe as well
which generation of FQ does Nalidixic acid belong to?
1st
Quinolones! not fluoro-
which generation of FQ does levofloxacin belong to?
3nd
which generation of FQ does moxifloxacin belong to?
4th (novel)
which generation of FQ do Norfloxacin, ciprofloxacin, and Ofloxacin belong to?
2nd
side effects of fluoroquinolones
GI distress
skin rash
phototoxicity
CNS effects (insomnia, dizziness, headache)
hepatotoxicity
tendinitis, Achilles rupture
QT prolongation–> cardiotoxicity (mainly 3rd and 4th generation)
teratogenic (cartilage and joint deformities)
*not for children< 10 y’
spectrum and clinical use of Nalidixic acid
gram - coverage (proteus, shigella, salmonella, campylobacter, E.coli)
UTI’s, prostatitis, GI tract infections
spectrum and clinical use of 2nd generation FQ (8)?
- gram - (including pseudomonas)
- gram + cocci
- mycobacteria (2nd line agents for TB)
- atypical agents (chlamydophila, mycoplasma)
- N. gonorrhoea (oral, single dose)
- Bacillus anthracis
- otitis externa (ciprofloxacin topical)
- uncomplicated UTI (cipro)
spectrum and clinical use of levofloxacin (3)?
- less active against gram -
- extended activity against gram +
(strep. pneumoniae, enterococci, MRSA) - most pathogens of community-acquired pneumonia(typical+atypical) –>’ respiratory FQ’
spectrum and clinical use of Moxifloxacin?
similar to 3rd generation (Levo) with
extended anaerobic coverage (broadest spectrum)
*not good for UTI
