Nucleic Acid Synthesis Inhibitors Part 2

What are the structural components of fluoroquinolones?

A carboxyl group, a fluorine atom, and a piperazine ring attached to a quinoline ring.

How do fluoroquinolones behave chemically?

They are amphoteric compounds with poor water solubility at pH 6–8.

Why are fluoroquinolones less effective in acidic urine?

They act as weak bases and have reduced activity in acidic environments.

What bacterial enzymes are inhibited by fluoroquinolones?

DNA gyrase (topoisomerase II) and topoisomerase IV.

What is the function of DNA gyrase?

It allows bacterial DNA to coil, uncoil, and rewind during replication and transcription.

Why is DNA gyrase essential for bacteria?

It relieves torsional stress and permits DNA replication and transcription.

What is the effect of inhibiting DNA gyrase and topoisomerase IV?

Disruption of DNA supercoiling, impaired DNA repair, and degradation of chromosomal DNA.

Why are mammalian cells minimally affected by fluoroquinolones?

Mammalian topoisomerases differ structurally from bacterial DNA gyrase.

Are fluoroquinolones bactericidal or bacteriostatic?

Bactericidal.

What is the post-antimicrobial effect of fluoroquinolones?

Persistent suppression of bacterial growth for 4–8 hours after drug exposure.

What are the first-generation quinolones?

Nalidixic acid and oxolinic acid.

Name the second-generation quinolones.

Ciprofloxacin, enoxacin, flumequine, norfloxacin, and ofloxacin.

Name the third-generation quinolones.

Danofloxacin, enrofloxacin, marbofloxacin, pefloxacin, and pradofloxacin.

Name the fourth-generation quinolones.

Moxifloxacin, gatifloxacin, trovafloxacin, gemifloxacin, and garenoxacin.

What is the spectrum of activity of fluoroquinolones?

Broad-spectrum against many Gram-negative organisms and several Gram-positive aerobes.

Which Gram-negative bacteria are usually susceptible to fluoroquinolones?

Escherichia coli, Klebsiella spp., Proteus spp., Salmonella spp., and Enterobacter spp.

Which fluoroquinolone has the greatest activity against Pseudomonas spp.?

Ciprofloxacin.

Which Gram-positive bacteria are commonly susceptible to fluoroquinolones?

Staphylococcus aureus, Staphylococcus pseudintermedius, and other Staphylococcus spp.

Which intracellular pathogen is notably susceptible to fluoroquinolones?

Brucella spp.

Which atypical organisms are susceptible to fluoroquinolones?

Mycoplasma, Rickettsia, and Chlamydia spp.

Which organisms are generally resistant to fluoroquinolones?

Obligate anaerobes and most enterococci.

Which additional organisms may be susceptible to fluoroquinolones?

Nocardia and atypical mycobacteria.

Which generations of fluoroquinolones have improved anaerobic activity?

Third- and fourth-generation fluoroquinolones.

How are fluoroquinolones absorbed after oral administration?

Rapidly, with nearly complete absorption in dogs, cats, and pigs.

How does food affect fluoroquinolone absorption?

It may delay absorption in monogastric animals.

Which substances reduce fluoroquinolone bioavailability?

Antacids containing calcium or magnesium due to chelation.

How are fluoroquinolones absorbed after IM or SC administration?

Rapidly, with nearly 100% bioavailability.

Where do fluoroquinolones distribute in the body?

They penetrate most tissues rapidly because of high lipid solubility.

Which organs contain especially high concentrations of fluoroquinolones?

Kidneys, liver, bile, prostate, bone, ocular fluid, endometrium, and CSF.

Do fluoroquinolones cross the placenta?

Yes.

Which white blood cells accumulate fluoroquinolones?

Phagocytic white blood cells.

What is the major route of fluoroquinolone elimination?

Renal excretion.

Which renal processes eliminate fluoroquinolones?

Glomerular filtration and tubular secretion.

How should fluoroquinolone dosing be adjusted in renal failure?

The dose should be reduced because clearance is impaired.

Which fluoroquinolone is metabolized to ciprofloxacin?

Enrofloxacin.

What is the major cartilage toxicity associated with fluoroquinolones?

Cartilage erosion leading to permanent lameness in growing animals.

Why do fluoroquinolones damage cartilage?

They chelate magnesium, disrupting chondrocyte function.

Why are fluoroquinolones contraindicated in young dogs?

They may cause irreversible cartilage damage during growth.

Which species is especially susceptible to fluoroquinolone-induced retinal degeneration?

Cats.

Which fluoroquinolone carries the greatest risk of retinal toxicity in cats?

Enrofloxacin.

Which fluoroquinolone is considered the least retinotoxic?

Pradofloxacin.

What causes retinal degeneration from fluoroquinolones?

Accumulation of photoreactive drug in the retina leading to reactive oxygen species formation.

What neurologic adverse effect may occur with high doses of fluoroquinolones?

Convulsions due to GABA receptor antagonism.

What gastrointestinal adverse effects are associated with fluoroquinolones?

Vomiting and diarrhea.

Which fluoroquinolones have been associated with antimicrobial-induced colitis?

Ciprofloxacin and moxifloxacin.

What is mitotoxicity?

Damage to mitochondrial topoisomerase or other mitochondrial structures caused by fluoroquinolones.

Which drugs interfere with GI absorption of fluoroquinolones?

Antacids, multivalent cations, and sucralfate.

Which urinary antiseptic decreases the efficacy of fluoroquinolones?

Nitrofurantoin.

Which drug group has increased toxicity when combined with fluoroquinolones?

Methylxanthines such as theophylline, caffeine, and theobromine.

Why do methylxanthines become toxic when given with fluoroquinolones?

Fluoroquinolones inhibit their metabolism, increasing serum concentrations.

Is cross-resistance common among fluoroquinolones?

Yes.

What are the major mechanisms of fluoroquinolone resistance?

Altered topoisomerases, decreased drug permeability, and increased efflux pumps.

Which enzyme is the primary resistance target in Gram-negative bacteria?

DNA gyrase.

Which enzyme is the primary resistance target in Gram-positive bacteria?

Topoisomerase IV.