Ch 40 - Quinoloneas, Folic Acid Antagonists, And Urinary Tract Antiseptics Flashcards
What is the predecessor to all fluoroquinolones?
Nalidixic acid
What gives us “collateral damage”?
- fluoroquinolones
- 3rd genereation cephalosporin
How does the fluoroquinolones enter the bacteria?
through porin channels
What is the pharmacological mechanism of action of fluoroquinolones?
- to G(-): they inhibit DNA gyrase (bacterial topoisomerase II)
- to G (+): topoisomerase IV
thus blocking bacterial DNA synthesis
What does the inhibition of topoisomerase IV do?
it impacts chromosomal stabilization during cell division, thus interfering with the separation of newly replicated DNA.
Are fluoroquinolones bactericidal or bacteriostatic?
bactericidal
What is fluoroquinolones effective against?
- G(-) organisms (E.coli, P. aerguinosa, Haemophilus influenzae)
- atypical organisms (Chlamydiaceae, Legionellaceae)
- G(+) organisms (streptococci)
- some mycobacteria (Mycobacterium tuberculosis)
Which fluoroquinolones are called the “respiratory fluoroquinolones”? and why?
- levofloxacin and moxifloxacin
- because they have excellent activity against S. pneumoniae
How are fluoroquinolones classified?
into generations
What is a part of the first generation of fluoroquinolones?
nonfluorinated quinolone -nalidixic acid-
What is a part of the second generation of fluoroquinolones? And why?
- Ciprofloxacin and norfloxacin
- because of their activity against aerobic gram-negative and atypical bacteria
What is a part of the third generation of fluoroquinolones? And why?
- levofloxacin
- because of its increased activity against gram-positive bacteria
What is a part of the fourth generation of fluoroquinolones? And why?
- moxifloxacin
- because of its activity against anaerobic and gram-positive bacteria
Norfloxacin (fluoroquinolones):
- poor oral bioavailability
- short half-life
- effective in treating nonsystemic infections, such as UTI, prostatitis, and infectious diarrhea
Ciprofloxacin (fluoroquinolones):
- used to treat systemic infections caused by gram-negative bacilli
- of the fluoroquinolones it has the best activity against
- used to treat traveler´s diarrhea (caused by E.coli) and typhoid fever (caused by salmonella)
- used as a second-line agent in the treatment of tuberculosis
Levofloxacin (fluoroquinolones):
- is the L-isomer of ofloxacin
- utilized in a wide range of infections, including prostatitis, skin infections, CAP, and nosocomial pneumonia
- 100%bioavailability
- dosed once daily
Moxifloxacin (fluoroquinolones):
- gram-positive organisms and anaerobes
- not used for UTIs
Resistance (fluoroquinolones):
- primarily due to chromosomal mutation in bacterial genes. Both topoisomerase IV and DNA gyrase may undergo mutations
- decreased accumulation
Which of the fluoroquinolones can be taken orally?
- ciprofloxacin
- levofloxacin
- moxifloxacin
- norfloxacin
- ofloxacin
Which of the fluoroquinolones can be taken IV?
- ciprofloxacin
- levofloxacin
- moxifloxacin
How is the distribution of fluoroquinolones?
- distributes well into all tissues and bodily fluids
- levels are high in bone, urine (except moxifloxacin), kidney, and prostatic tissue (but not prostatic fluid)
- concentration in the lungs exceed those in serum
Elimination of fluoroquinolones:
- excreted renally
- dose adjustment in patients with renal dysfunction
- moxifloxacin is excreted primarily by the liver, no doe adjustment is required for renal impariment
Adverse reactions to fluoroquinolones:
- CNS effects: headache, dizziness, insomnia
- GI effects: diarrhea, nausea, abnormal liver function tests
- Photosensistivity
- Tendinitis or tendon rupture
(p. 516)
Can fluoroquinolones be used in children?
no, because they cause cartilage erosion, which also rules out their use during pregnancy and nursing
