DNA synthesis inhibitors: Fluoroquinolones

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DNA synthesis inhibitors: Fluoroquinolones

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USMLE® Step 1 style questions USMLE

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USMLE® Step 2 style questions USMLE

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A 67-year-old woman presents to the clinic with a productive cough that developed two days ago. She has had increased production of green-brown sputum and dyspnea. Past medical history is significant for atrial fibrillation, hypertension, hypercholesterolemia, and iron-deficiency anemia. Current medications include metoprolol, ferrous sulfate, hydrochlorothiazide, atorvastatin, and aspirin. Temperature is 38.1°C (100.6°F), blood pressure is 128/79 mmHg, pulse is 86/min, and respiratory rate is 15/min. On physical examination, the patient has bronchial breath sounds and dullness to percussion in the area of the left lower lung. Rapid influenza testing is negative. Community-acquired pneumonia is suspected, and she is started on a seven-day course of levofloxacin. Which medications should be discontinued while the patient is taking levofloxacin?  

External References

First Aid

2024

2023

2022

2021

Ciprofloxacin

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

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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.