Fluoroquinolones Flashcards
What is the mechanism of action of fluoroquinolones?
Fluoroquinolones inhibit bacterial DNA gyrase (topoisomerase II) and topoisomerase IV, preventing DNA replication and causing double-stranded DNA breaks (bactericidal).
This action is crucial for the bactericidal effect of fluoroquinolones.
Describe the spectrum of activity of fluoroquinolones.
Broad spectrum:
* Excellent Gram-negative coverage (including Enterobacteriaceae; ciprofloxacin and levofloxacin cover Pseudomonas)
* Moderate Gram-positive coverage (newer agents like levofloxacin, moxifloxacin cover Streptococcus spp.)
* Atypicals (Mycoplasma, Chlamydia, Legionella)
* Moxifloxacin also covers many anaerobes; others have poor anaerobic activity.
This makes fluoroquinolones versatile in treating various infections.
What are the common mechanisms of resistance to fluoroquinolones?
Resistance can occur via:
* Mutations in DNA gyrase or topoisomerase IV genes (altered target binding)
* Increased efflux pump activity
* Plasmid-mediated qnr proteins that protect topoisomerases.
* Rapid resistance emerges if used alone in Staph or Pseudomonas.
Understanding these mechanisms is essential for effective antibiotic stewardship.
Outline key pharmacokinetic features of fluoroquinolones.
Most fluoroquinolones are:
* Well-absorbed orally (~80-100% bioavailability)
* Distributed widely (some into bone, prostate; moxifloxacin penetrates CSF)
* Absorption significantly reduced by divalent/trivalent cations (e.g., antacids, iron, calcium due to chelation)
* Primarily eliminated renally (high urine levels) except moxifloxacin (hepatic elimination)
* Generally once or twice daily dosing due to long half-lives.
These pharmacokinetic properties influence dosing and administration.
What are major drug interactions with fluoroquinolones?
Major drug interactions include:
* Antacids, sucralfate, iron, calcium, and other cation supplements chelate fluoroquinolones and reduce their absorption
* Some (ciprofloxacin, ofloxacin) can inhibit CYP1A2, potentially raising levels of theophylline or warfarin
* Additive QT prolongation with other QT-prolonging drugs (especially moxifloxacin)
* Concurrent corticosteroids increase risk of tendon rupture.
Awareness of these interactions is critical for patient safety.
What are common clinical indications for fluoroquinolone use?
Fluoroquinolones are used for:
* UTIs (including pyelonephritis) and prostatitis, especially caused by Gram-negatives
* Travelers’ diarrhea and Pseudomonas UTIs (ciprofloxacin)
* Community-acquired pneumonia (levofloxacin or moxifloxacin covers atypicals)
* Osteomyelitis by Gram-negatives
* Acute diarrheal illnesses (Shigella, Salmonella)
* Anthrax (ciprofloxacin is first-line for inhalational anthrax).
These indications highlight the importance of fluoroquinolones in treating serious infections.
In which populations or conditions are fluoroquinolones contraindicated or used with caution?
Avoid in:
* Pregnant women and in children (<18) due to potential cartilage damage (arthropathy)
* Children and older patients on steroids due to increased tendon rupture risk
* Patients with myasthenia gravis (can exacerbate muscle weakness)
* Dose adjust in renal impairment (except moxifloxacin).
These considerations are vital for prescribing fluoroquinolones safely.
List major adverse effects and toxicities of fluoroquinolones.
Major adverse effects include:
* GI upset (nausea, diarrhea)
* Neurotoxic effects (headache, dizziness, insomnia; rarely seizures)
* Tendonitis and tendon rupture (Achilles tendon, especially in older adults or with steroid use)
* Cartilage damage in animals (hence contraindicated in children/pregnancy)
* QT interval prolongation (risk of Torsades, especially with moxifloxacin)
* Peripheral neuropathy
* Increased risk of C. difficile colitis.
Monitoring for these effects is essential during treatment.
What is a high-yield mnemonic for fluoroquinolones?
“Fluoroquinolones hurt attachments to your bones” – highlighting the risk of tendon damage (especially Achilles tendon rupture).
Mnemonics can aid in remembering important safety information.
