Inhibitors of DNA/RNA synthesis Flashcards
What are the classes associated with inhibitors of DNA/RNA synthesis?
fluoroquinolones
lipopeptides
What are the drugs in the class of fluoroquinolones?
- besifloxacin
- ciprofloxacin
- gatifloxacin
- gemifloxacin
- levofloxacin
- moxifloxacin
- norfloxacin
- ofloxacin
What is the mechanism of action for fluoroquinolones?
bactericidal
interfere with DNA syntehsis by inhibiting 1 of 2 enzymes
- DNA gyrase
- topoisomerase IV
What is the enzyme DNA gyrase responsible for?
relaxing supercoiled DNA
essential for replication, transcription, and DNA repair
What is the enzyme topoisomerase IV action?
separating DNA into daughter cells during replication
Which fluoroquinolone is least likely for a bacteria to develop resistance? why?
gemifloxacin because it is especially effective at inhibiting both enzymes
bacteria must acquire mutations in 2 different enzymes for resistance
What can interfere with absorption of fluoroquinolones?
food or cations (Ca, Fe, Al, Mg, Zn)
sucralfate
Where do fluoroquinolones distribute?
nearly all body compartments
minimal in the CNS
What drug is associated with lipopeptides?
daptomycin
What is the mechanism of action for daptomycin?
binds to bacterial membranes causing rapid depolarization of the cell
loss of membrane potential brings DNA,RNA and protein synthesis to a halt resulting in cell death
How is daptomycin excreted?
unchanged in the urine
What drugs have distinct mechanisms of action?
metrondazole
nitazoxanide
tinidazole
What type of bacteria does metronidazole inhibit or stop growth? What is the mechanism of action of metronidazole?
- selectively absorbed by anaerobic bacteria
- sensitive protozoa
nonenzymatically reduced by reacting with reduced ferredoxin that is generated by pyruvate/ferredoxin oxido-reductase
The reduction reaction of metronidazole causes what?
production of metabolites toxic to anaerobic cells
result in inhibition of DNA synthesis, degradation of existing DNA, DNA strand breaks, and inhibition of nucleic acid synthesis => cell death
What is the mechanism of action of nitazoxanide?
similar to metronidazole
interferes with pyruvate/ferredoxin oxidoreductase enzyme-dependent electron transfer that is essential for anaerobic metabolism
