Quinolones

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Quinolones

  1. 1. Dr.Rahul Asso. Prof. pharmacology RMC, PIMS (DU)
  2. 2.  Bactericidal broad spectrum drugs  Increasingly used because of their relative safety, their availability both orally and parenterally and their favorable pharamacokinetics  There is increasing concern about the emergence of resistance to these agents  Parent drug: nalidixic acid
  3. 3. Generation Drug Names Spectrum 1st Nalidixic acid Cinoxacin Gram- but not Pseudomonas 2nd Norfloxacin Ciprofloxacin Ofloxacin Gram-(including Pseudomonas) some Gram+ (S. aureus) some atypicals 3rd Levofloxacin Sparfloxacin Moxifloxacin Gemifloxacin Same as 2nd generation: extended Gram+ and atypical coverage 4th *Trovafloxacin Same as 3rd generation: broad anaerobic coverage*withdrawn from the market in 1999
  4. 4. Older agents with poor activity; newer FQs with enhanced potency • Methicillin-susceptible Staphylococcus aureus • Streptococcus pneumoniae (including PRSP) • Group and viridans streptococci – limited activity • Enterococcus sp. – limited activity
  5. 5. (cipro=levo>gati>moxi) • E. coli, Klebsiella sp, • Enterobacter sp, Proteus sp • Salmonella Shigella, • Serratia marcescens, H. influenzae, • M. catarrhalis, Neisseria sp. • Pseudomonas aeruginosa significant resistance has emerged; ciprofloxacin and levofloxacin with best activity
  6. 6. – All FQs have excellent activity against atypical bacteria including:  Legionella pneumophila - DOC  Chlamydia sp.  Mycoplasma sp.  Ureaplasma urealyticum
  7. 7.  Enzymes required for DNA replication 1.Topoisomerase II (DNA gyrase): GyrA and GyrB 2.Topoisomerase IV: ParC and ParE  Mechanism of DNA gyrase
  8. 8.  Inhibit bacterial DNA synthesis by inhibiting DNA gyrase and topoisomerase IV  rapid cell death  Mostly Topo II inhibition in G- bacterias  Topo IV inhibition more in G+ bacterias  Post antibiotic effect: lasts 1 to 2 hours, increases with increasing concentration
  9. 9.  Absorption - good oral availability, but food will inhibit, as well as Al, Ca, Mag, Fe.  Distribution - good tissue penetration, including prostate, bile, lung. Poor CNS coverage  Elimination – renal (for 1st generation)  PD: Concentration dependent killing
  10. 10.  UTI  Bacterial gastroenteritis  Intra abdominal infections  Typoid fever  Gonorrehea  MDR- tuberculosis  Leprosy  Osteomyelitis  Invasive otitis media  Nosocomial pneumonia  Septicemia  Bacterial conjuctivitis  Chronic bronchitis  Sinusitis  Anthrax
  11. 11.  Most commonly used antimicrobials  Very effective against E.coli, proteus, Enterobacteriace  Higher urine conc. than serum conc.good for complicated renal cysts & recurrent UTI from prostatitis  Ciprofloxacin 750mg bd X 3 wks
  12. 12.  Very effective against shigella, salmonella,, E.coli.  Norfloxacin, ciprofloxacin , ofloxacin are effecive
  13. 13. (Comparative studies) 1) ciprofloxacin + metronidazole 2) Imipenem 3) Trovafloxacin 4) amoxicillin/clavulanate similar activity
  14. 14.  Ciprofloxacin 750mg BD X 10 days  Pefloxacin, Ofloxacin can also be used
  15. 15.  Cervicitis  Urethritis  PID  Single dose :Cipro..500mg, Oflox. 400mg  Problem : resistance  So Ceftriaxone first drug of choice
  16. 16.  MDR tuberculosis  MAC infections  Leprosy (ROM theraphy)
  17. 17.  Trovafloxacin approved by the FDA for treatment of soft-tissue infections, including DM foot  Levofloxacin Superior to ciprofloxacin in SSTI caused by S. aureus
  18. 18. Community-acquired Pneumonia  Outpatients : new fluoroquinolones  Hospitalized General wards : new FQs monotherapy ICU : -lactam + new FQs Upper respiratory infections : acute sinusitis, chronic bronchitis
  19. 19.  Prophylaxis and treatment of infections in neutropenic patients  Conjunctivitis due to G-ve bacteria  Invasive otitis media  Prophylaxis and exposure Anthrax  Respiratory infection : (Levofloxacin)  Chronic bronchitis  Nosocomial pneumonia  Sinusitis
  20. 20.  Gastrointestinal – 5 %  Nausea, vomiting, diarrhea, dyspepsia  Central Nervous System  Headache, agitation, insomnia, dizziness, rarely,  hallucinations and seizures (elderly)  Hepatotoxicity  LFT elevation (led to withdrawal of trovafloxacin)  Phototoxicity (uncommon with current FQs)  More common with older FQs (halogen at position 8)  Cardiac  Variable prolongation in QTc interval  Led to withdrawal of grepafloxacin, sparfloxacin
  21. 21.  Articular Damage  Arthopathy including articular cartilage damage, arthralgias, and joint swelling  contraindication in pediatric patients and pregnant or breast feeding women  Risk versus benefit  Other adverse reactions:  Tendon rupture,  Dysglycemias,  Hypersensitivity
  22. 22. Fluroquinolone Doses Preferred Uses Norloxacin 400mg OD/BD UTI Bacterial Diarrheoas Ciprofloxacin 250-750mg BD UTI Typhoid Bacterial diarrheoas Gonorrhea…etc Ofloxacin 200-400mg BD Tuberculosis Leprosy Atypical Pneumonia Chlamydial infections Levofloxacin 500mg OD Community aquired pnumonia Bronchitis, UTI Skin & soft tissue infections Gatifloxacin Community aquired pnumonia Bronchitis, UTI Gonnococcal infections Moxifloxacin Community aquired pnumonia

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