Epistemis

Fluoroquinolones

  • Inhibitors of Cellular Replication and Topology

Fluoroquinolones are rapid bactericidal agents with excellent absorption and tissue penetration. They are classified by generation, from pure urinary compounds to agents with respiratory and anaerobic coverage.

Mechanism

💊 Generic and Commercial Names

Segunda Gen: Ciprofloxacina (Cipro). Tercera Gen: Levofloxacina (Tavanic). Cuarta Gen: Moxifloxacina (Actira, Octegra).

🔬 Pharmacological Group

Fluoroquinolonas (anillo de 4-quinolona fluorado). Inhibidores de las ADN topoisomerasas bacterianas.

Mechanism of Action

Su blanco bloquea las enzimas responsables del enrollamiento celular:

  • Bloqueo de la ADN Girasa (Topoisomerasa II) en Gram-Negativos: Se unen específicamente al complejo ADN-girasa bacteriano durante la replicación, impidiendo el paso de resellado de las hebras dobles de ADN cortadas durales necesarias para aliviar la tensión helicoidal. Esto provoca la persistencia de roturas de doble cadena en el cromosoma de forma letal.
  • Bloqueo de la Topoisomerasa IV en Gram-Positivos: Se dirigen de forma selectiva hacia esta enzima dural, la cual es responsable de la decatenación (separación de los cromosomas hijos replicados entrelazados) al finalizar el ciclo mitótico bacteriano. Al bloquear este paso, detienen la división celular.

Pharmacokinetics

Key Pharmacokinetics

Parameter Ciprofloxacin Moxifloxacin
Routes of AdministrationOral, IV, Ophthalmic, Optic.Oral and slow IV (minimum of 60 minutes).
Dural absorptionExcellent oral bioavailability (~70-80%), chelator of metal cations.Extraordinary oral bioavailability (~90%), rapid dural absorption not modified by fatty foods.
Volume of Distribution (Vd)High (2.0 - 2.5 L/kg). Excellent penetration into lung parenchyma, prostate, bone and bile.High (2.0 to 2.8 L/kg). High intracellular distribution in macrophages and bronchial tissue.
Protein BindingLow (~20-30%).Moderate (~40-50%).
Excretion and Half-LifeRenal glomerular excretion and tubular secretion active by 50-70%. Half-life of 4.0 to 5.0 hours.Purely hepatic and biliary clearance into feces (80%). Long half-life of 12.0 hours.

Antimicrobial Spectrum

  • Ciprofloxacin: Maximum potency for aerobic Gram-negative bacilli, including Pseudomonas aeruginosa, and common enterobacteria. It lacks useful coverage for pneumococcus or atypicals with a robust systemic form.
  • Levofloxacin: Respiratory course spectrum. It retains Gram-negative coverage (including Pseudomonas spp. at high doses) and adds excellent potency against Streptococcus pneumoniae and atypicals.
  • Moxifloxacin: Excellent against S. pneumoniae, atypical respiratory course and anaerobic microorganisms. It has no activity against Pseudomonas aeruginosa nor is it eliminated in urine, being contraindicated for urinary tract infections (UTI).

Indicators and dose

Dosage and Adjustment

  • Ciprofloxacin: 500 to 750 mg every 12 hours orally, or 400 mg every 8 to 12 hours IV.
  • Levofloxacin: 500 to 750 mg every 24 hours orally or IV.
  • Moxifloxacin: 400 mg every 24 hours orally or IV. No adjustment required in renal failure.
  • Adjustment of Levofloxacin in Renal Failure:
    • Clcr 20-49 mL/min: Administer 500 mg as a loading dose, followed by 250 mg every 24 hours.
    • Clcr < 20 mL/min: Administer 500 mg in a loading dose, followed by 250 mg every 48 hours.

Security

Contraindications and ADRs

  • Contraindications: Growing children; history of quinolone tendinopathy; Acquired prolonged QTe interval.
  • Adverse Effects (ADR):
    • Tendinopathy and Achilles Tendon Rupture: Quinolones exert direct toxicity on the collagen and chondrocytes of cartilage and tendons by chelating intracellular magnesium, causing fibrillar weakness. This risk is higher in elderly people who concomitantly consume systemic corticosteroids.
    • Aortic Aneurysm and Aortic Dissection: Increase in the degradation of systemic tissue collagen mediated by metalloproteinases, weakening the major arterial vascular wall.
    • Neuropsychiatric Effects: Transient delirium, mental confusion, refractory hallucinations and seizures (due to blockade of GABAA receptors and stimulation of cortical NMDA in the elderly).
    • QTe Interval Prolongation: Greater with Moxifloxacin.

FDA Warning on the Use of Fluoroquinolones

Due to the risk of disabling adverse effects of irreversible course affecting the musculoskeletal system (tendonitis, tendon ruptures, severe arthralgias) and central neurological system (paresthesias, psychosis, delirium), international regulatory agencies recommend avoiding the use of fluoroquinolones for mild self-limiting infections (such as acute sinusitis, acute bronchitis or uncomplicated cystitis) if alternatives exist. safe first-line therapeutics available.

Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.

PreviousCyclic Lipopeptides and Polymyxins
System
Antimicrobial and Infectious
Cluster
Inhibitors of Cellular Replication and Topology
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