DNA Synthesis Inhibitors (Fluroquinones)

What are the three fluoroquinolones you should know?

Ciprofloxacin (Cipro), Levofloxacin, and Moxifloxacin.

What is the test-level mechanism of action of fluoroquinolones?

They inhibit DNA gyrase, preventing bacterial DNA replication.

Which bacterial enzyme is also called DNA gyrase?

Topoisomerase II.

What does topoisomerase II normally do?

It coils and uncoils bacterial DNA so DNA repair and replication can occur.

What does topoisomerase IV normally do?

It separates replicated chromosomal DNA into the respective daughter cells.

Are fluoroquinolones bactericidal or bacteriostatic?

Bactericidal.

What is the difference between "quinolones" and "fluoroquinolones" for this course?

The three tested drugs are fluoroquinolones, although the professor may call them quinolones.

How does oral fluoroquinolone absorption compare with IV dosing?

Oral absorption produces blood levels comparable to IV dosing.

How well do fluoroquinolones penetrate the CSF?

Poorly.

How are most fluoroquinolones eliminated?

Through the kidneys; renal dysfunction may require dosage adjustment.

Which fluoroquinolone is eliminated by the liver instead of the kidneys?

Moxifloxacin.

What dosage forms are available for fluoroquinolones?

Oral, IV, Ophthalmic (eye), and Otic (ear).

Why is fluoroquinolone resistance increasing?

Widespread overuse has increased resistance, especially in Pseudomonas and Staphylococci.

What are the two major mechanisms of fluoroquinolone resistance?

Alteration/mutation of DNA gyrase, and decreased bacterial permeability limiting drug entry.

What are the common GI adverse effects of fluoroquinolones?

Nausea, vomiting, and diarrhea.

What is the boxed warning associated with fluoroquinolones?

Tendinitis and tendon rupture, especially involving the Achilles tendon.

When can fluoroquinolone-associated tendon injury occur?

During therapy or even well after therapy.

Which patients have increased risk of fluoroquinolone-associated tendon rupture?

Older adults, patients taking glucocorticoids, and transplant patients.

What CNS effects can fluoroquinolones cause?

Headache/dizziness, confusion/memory problems, tremor, and seizures.

When is fluoroquinolone-associated peripheral neuropathy more likely?

With prolonged therapy, such as a long course for a bone infection.

What cardiac adverse effect is associated with fluoroquinolones?

QT-interval prolongation.

What dangerous rhythm can result from marked QT prolongation?

Torsades de pointes.

When is fluoroquinolone-related QT prolongation especially concerning?

With congenital long-QT syndrome or when multiple QT-prolonging drugs are combined.

In which neuromuscular disorder should fluoroquinolones be avoided?

Myasthenia gravis.

Why should fluoroquinolones be avoided in myasthenia gravis?

Their neuromuscular-blocking activity can worsen muscle weakness.

Why are fluoroquinolones generally avoided during pregnancy and in patients younger than 18?

They may inhibit cartilage development.

Do you need to memorize the specific fluoroquinolone CYP enzymes or the full list of QT-prolonging drugs?

No; know clinically important interactions can occur, but do not memorize specific lists.

Which products reduce fluoroquinolone absorption?

Multivalent cations found in calcium, iron, magnesium, zinc, aluminum, antacids, and multivitamins.

Why do multivalent cations reduce fluoroquinolone absorption?

They bind the antibiotic in the GI tract, preventing absorption and risking treatment failure.

How should a fluoroquinolone be separated from multivalent cations?

Take fluoroquinolone 2 hours before or wait 4 hours after the supplement.

What is Ciprofloxacin's basic spectrum?

Weak Gram-positive, strong Gram-negative (including Pseudomonas), and no anaerobic coverage.

Why should Ciprofloxacin not be relied on for routine Staph, Strep, skin, or throat infections?

Its Gram-positive activity is weak and resistance has reduced its reliability.

Which fluoroquinolone is most strongly associated with Gram-negative organisms and Pseudomonas?

Ciprofloxacin.

What are the major urinary uses of Ciprofloxacin?

Complicated UTI, catheter-related UTI, and prostatitis.

What GI infections can Ciprofloxacin treat?

Severe gastroenteritis or diarrhea caused by Salmonella or Shigella.

What other clinical uses are associated with Ciprofloxacin?

Topical eye/ear, bone/joint, hospital pneumonia (Gram-negative), anthrax, and tularemia.

What is the easiest way to remember Ciprofloxacin?

Cipro = Gram-negative organisms + Pseudomonas.

Which fluoroquinolones are considered respiratory quinolones?

Levofloxacin and Moxifloxacin.

What makes Levofloxacin and Moxifloxacin "respiratory quinolones"?

Expanded Gram-positive coverage (especially Streptococcus pneumoniae) plus atypical coverage.

Which atypical organisms are covered by the respiratory quinolones?

Legionella and Chlamydia.

What is Levofloxacin's basic spectrum?

Stronger Gram-positive respiratory, atypical, and Gram-negative (including Pseudomonas) coverage.

Which respiratory fluoroquinolone covers Pseudomonas?

Levofloxacin.

Which respiratory fluoroquinolone covers Salmonella and Shigella according to the slide?

Levofloxacin only.

What respiratory infections can Levofloxacin treat?

Respiratory tract infections, including pneumonia and sinus/bronchial infections.

What urinary and prostate infections can Levofloxacin treat?

Complicated UTI, pyelonephritis, and prostatitis.

What additional uses are associated with Levofloxacin?

Intra-abdominal infection, Pseudomonas infection, traveler's diarrhea, and Chlamydia.

What is the easiest way to distinguish Levofloxacin?

Levo = respiratory quinolone that still covers Pseudomonas.

What makes Moxifloxacin unique among the three fluoroquinolones?

Covers anaerobes, eliminated by the liver, and does not cover Pseudomonas.

Does Moxifloxacin have Gram-negative coverage?

Yes, but it does not cover Pseudomonas.

Which fluoroquinolone has the best anaerobic coverage?

Moxifloxacin.

What infections can Moxifloxacin treat?

CAP, acute bacterial sinusitis, bacterial conjunctivitis, intra-abdominal, and mycobacterial infections.

How can Moxifloxacin be used in tuberculosis treatment?

It may appear in alternative mycobacterial/TB regimens rather than the primary regimen.

Which fluoroquinolones cover Pseudomonas aeruginosa?

Ciprofloxacin and Levofloxacin.