Fluroquinolones 2

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Fluroquinolones 2

  1. 1. DR.VIJAY NAGDEV H.O. MEDICAL UNIT-I CHANDKA MEDICAL COLLEGE LARKANA
  2. 2. Background <ul><li>In 1962 nalidixic acid was discovered by George lesher during synthesis of chloroquine and was named as quinolone </li></ul><ul><li>Fluoroquinolones were derived by adding flourine atom in nalidixic acid. </li></ul>
  3. 3. <ul><li>Earlier quinolones were useful only for treatment of UTI. </li></ul><ul><li>Fluorinated derivatives achieve bactericidal levels in blood and tissues so they have improved antibacterial spectrum. </li></ul>
  4. 4. MECHANISM OF ACTION <ul><li>Fluroquinolones are bactericidal agents </li></ul><ul><li>They block bacterial DNA synthesis by inhibiting bacterial DNA gyrase and topoisomerase IV. </li></ul><ul><li>Inhibition of DNA gyrase prevents the relaxation of positively supercoiled DNA that is required for normal transcription and replication </li></ul>
  5. 5. Cont…. <ul><li>Inhibition of topoisomeraseIV interferes with separation of replicated chromosomal DNA into the respective daughter cells during cell division. </li></ul><ul><li>They can enter cells easily via porins and are used to treat intracellular pathogens ( Legionella, pneumophila and Mycoplasma) </li></ul>
  6. 6. RESISTANCE <ul><li>Resistance is due to </li></ul><ul><li>one or more point mutations in the quinolone binding region of the target enzyme </li></ul><ul><li>OR to a change in the permeability of the organism </li></ul><ul><li>Resistance to one FQL confers cross resistance to all members of the class. </li></ul>
  7. 7. <ul><li>CLASSIFICATION </li></ul>
  8. 8. Generations Drugs Spectrum 1 st (Quinolone) Nalidixic acid Cinoxacin Gram-ve but not Pseudomonas species 2nd Norfloxacin Ciprofloxacin Enoxacin Ofloxacin Gram- ve(including Pseudomonas species), some Gram+ (S. aureus) and some atypicals 3rd Levofloxacin Sparfloxacin Moxifloxacin Gemifloxacin Same as 2 nd generation with extended Gram+ve and atypical coverage 4th *Trovafloxacin Same as 3 rd generation with broad anaerobic coverage
  9. 9. Pharmacokinectics <ul><li>Well absorbed orally with bioavailability 80-95% almost equal to i.v. </li></ul><ul><li>Half life 3-10 hours </li></ul><ul><li>Oral absorption impaired by divalent cations(Antacids containg Mg, Ca,or AL ). </li></ul><ul><li>Most of fluoroquinolones eleminated by renal mechanism so adjustment required in patients with creatinine clearance <50 ml/min. </li></ul><ul><li>Limited CSF penetration. </li></ul>
  10. 10. Distribution <ul><li>[Conc] > serum: </li></ul><ul><ul><li>Prostate tissue </li></ul></ul><ul><ul><li>Stool </li></ul></ul><ul><ul><li>Bile </li></ul></ul><ul><ul><li>Lung </li></ul></ul><ul><ul><li>Kidneys </li></ul></ul><ul><ul><li>Neutrophils </li></ul></ul><ul><ul><li>Macrophages </li></ul></ul><ul><li>[Conc] < serum: </li></ul><ul><ul><li>Prostatic fluid </li></ul></ul><ul><ul><li>Bone </li></ul></ul><ul><ul><li>CSF </li></ul></ul>
  11. 11. Drug interactions Drugs increasing levels of FQL FQL increasing the levels of : Theophyline Antidepressants NSAIDS Imipramine corticosteroids Caffene Theophyline Warfarin (INR –monitored)
  12. 14. Adverse effects. <ul><li>Generally safe antibiotics </li></ul><ul><li>G.I.T -nausea,vomiting,diarrhea and antibiotic associated colitis have been reported. </li></ul><ul><li>CNS -confusion,insomnia,dizziness,anxiety,and seizures(displacement of GABA from its receptors). </li></ul><ul><li>CVS -torsade de pointes,prolonged QTc interval. </li></ul><ul><li>May damage growing cartilage resulting in arthropathy(but that’s reversible so may b used in psudomonal infections in C.F where benefit outweighs the risk.) </li></ul>
  13. 15. Cont. <ul><li>Tendonitis and tendon rupture is rare but very serious. </li></ul><ul><li>Phototoxicity-avoid excesive sun exposure. </li></ul><ul><li>Leukopenia,eosinophilia (rare) </li></ul><ul><li>Mild elevation in transaminases (rare) </li></ul>
  14. 16. Contraindication <ul><li>Childrens (not absolute) </li></ul><ul><li>Pregnancy </li></ul><ul><li>Lactation </li></ul><ul><li>Epilepsy </li></ul><ul><li>QTc prolongation </li></ul>
  15. 17. <ul><li>Commonly used Fluoroquinolones </li></ul>
  16. 18. Ciprofloxacin <ul><li>2 nd generation fluoroquinolone </li></ul><ul><li>Mainly effective against G –ve bacteria : </li></ul><ul><li>Enterobacteriacae H. influenzae M. catarrhalis </li></ul><ul><li>Campylobacter Pseudomonas N. gonorrheae </li></ul><ul><li>Intracellular pathogens </li></ul><ul><li>M. Tuberculosis Mycoplasma Chlamydia </li></ul><ul><li>Legionella Brucella </li></ul><ul><li>Not effective against G+ and anaerobes </li></ul>
  17. 19. Clinical uses <ul><li>1.Urinary tract infections (G- bacteria) </li></ul><ul><li>2. Osteomyelitis due to P. aeruginosa </li></ul><ul><li>3. Gonorrhea </li></ul><ul><li>4. Travellers’ diarrhea- ciprofloxacin commonly used </li></ul><ul><li>5. Tuberculosis </li></ul><ul><li>6. Prostatitis </li></ul><ul><li>7. Community- acquired pneumoniae </li></ul><ul><li>8. Diabetic foot infections ( P. aeruginosa ) </li></ul><ul><li>9.Anthrax </li></ul>
  18. 20. <ul><li>Usual duration is 7-14 days </li></ul><ul><li>Available forms </li></ul><ul><li>Brand name : ciproxin(bayer),cycin. </li></ul>Oral Parentral Opthalmic 100 mg 200 mg iv 3mg/ml solution 250 mg 400 mg iv 3.3mg/mg ointment 500 mg
  19. 21. Levofloxacin <ul><li>3 rd generation fluoroquinolone </li></ul><ul><li>Spectrum: Gram-ve, Gram+ve (S. aureus including MRSA & S. pneumoniae) and Legionella pneumophila, atypical resp. pathogens, </li></ul><ul><li>Mycobacterium tuberculosis </li></ul><ul><li>Indications: </li></ul><ul><ul><li>Chronic bronchitis and CAP </li></ul></ul><ul><ul><li>Nosocomial pneumonia </li></ul></ul><ul><ul><li>Intra-abdominal infections </li></ul></ul>
  20. 22. Cont. <ul><ul><li>Adverse reaction. </li></ul></ul><ul><ul><li>Blood glucose disturbances in DM patients </li></ul></ul><ul><ul><li>QTC prolongation, torsades de pointes, arrhythmias </li></ul></ul><ul><ul><li>Nausea, GI upset </li></ul></ul><ul><ul><li>Interstitial nephritis </li></ul></ul>
  21. 23. <ul><li>Usual duration same 7-14 days </li></ul><ul><li>Available forms </li></ul><ul><li>Brand name:leflox,l-cyn,qumic </li></ul>Oral Parentral Opthalmic 100 mg 5 mg/ml iv 5mg/ml solution 250 mg 25 mg/ml iv 500mg

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