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QUINOLONES

QUINOLONES. Classification. Quinolones (1 st generation) Highly protein bound Mostly used in UTIs Fluoroquinolones (2 nd , 3 rd and 4 th generation) Modified 1 st generation quinolones Not highly protein bound Wide distribution to urine and other tissues; limited CSF penetration.

lilah-alvarez
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QUINOLONES

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  1. QUINOLONES

  2. Classification • Quinolones (1st generation) • Highly protein bound • Mostly used in UTIs • Fluoroquinolones (2nd, 3rd and 4th generation) • Modified 1st generation quinolones • Not highly protein bound • Wide distribution to urine and other tissues; limited CSF penetration.

  3. *withdrawn from the market in 1999

  4. Mechanism of Action • Dual MOA: • Inhibition of bacterial DNA Gyrase (Topoisomerase II) • Formation of quinolone-DNA-Gyrase complex • Induced cleavage of DNA • Inhibition of bacterial Topoisomerase IV • Mechanism poorly understood Mechanism of DNA Gyrase

  5. Mechanism of Action

  6. [Conc] > serum: Prostate tissue Stool Bile Lung Neutrophils Macrophages Kidneys [Conc] < serum: Prostatic tissue fluid Bone CSF Quinolones

  7. Quinolones • Drug interactions: • ↓ absorption: Al3+, Mg2+, and Ca2+ antacids • CYP450 inhibition potential drug interactions for ciprofloxacin • (Ex) can increase warfarin exposure (real changes in INR are rare, but monitor) • Adverse effects: • GI: Nausea, vomiting • CNS: HA, dizziness, confusion, insomnia, delerium, hallucinations, seizure (rare) • Cardiovascular: Torsades de pointes (rare) • Musculoskeletal: Rupture of tendon (rare) • Neurologic: Polyneuropathy (rare)

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