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for Crohn disease p. 389
cytochrome P-444 and p. 251
fluoroquinolones p. 192
mechanism (diagram) p. 184
meningococci p. 140
Mycobacterium avium- intracellulare p. , 193
prophylaxis p. 194
Pseudomonas aeruginosa p. , 141
Our bodies consist of eukaryotic cells, while bacterias consist of prokaryotic cells.
So, in order to treat bacterial infections we can develop antimicrobials that only target prokaryotic cells while leaving our cells mostly unharmed.
One of these targets is bacterial DNA, and we call these medications DNA inhibitors or nucleic acid inhibitors.
There are plenty of processes and enzymes involved that we can target and the quinolones and fluoroquinolones inhibit an enzyme called DNA topoisomerase.
So there are many different types of topoisomerases but we’ll be looking at topoisomerase II, also called DNA gyrase, and topoisomerase IV.
Both types of topoisomerases cause double strand breaks in DNA, but at different points during mitosis.
Topoisomerase II plays a role in condensing the chromosomes by making a double strand break in the DNA so that it can be more tightly wound, causing a supercoil.
When enough supercoils are induced, the DNA condenses.
Topoisomerase IV plays a role later on, after the chromosome has been replicated, where it causes a double strand break in the DNA so the new DNA strand can be disentangled from the original.
Now, quinolones are created to target bacterial topoisomerases, but it was soon discovered that by adding a fluorine molecule to the quinolones, they become more effective.
So these newer medications, called fluoroquinolones, replaced the older quinolones in most clinical settings.
Common fluoroquinolones include ciprofloxacin, ofloxacin, balofloxacin, levofloxacin, gemifloxacin, and moxifloxacin.
One way to tell a fluoroquinolone apart from other antimicrobials is that they all have the suffix “-floxacin.”
These medications can be taken peroral or via IV, but ciprofloxacin and ofloxacin are also available in otic formulations, while moxifloxacin is also available in ophthalmic solutions.
Now fluoroquinolones are broad spectrum bactericidal antibiotics and ciprofloxacin in particular is widely used.
They are very effective against gram negative bacterias like Enterobacteriaceae, Haemophilus, Legionella, Neisseria, Moraxella, and even Pseudomonas species.
They are also effective against certain mycobacteria and can be used for the treatment of tuberculosis.
However, more and more bacteria are becoming resistant to ciprofloxacin, either through mutations in the genes that code of topoisomerases, or through efflux pumps that pump the medication out.
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