Fluoroquinolones

  • 2,319 views
Uploaded on

 

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
No Downloads

Views

Total Views
2,319
On Slideshare
0
From Embeds
0
Number of Embeds
1

Actions

Shares
Downloads
208
Comments
2
Likes
1

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide

Transcript

  • 1. DR.VIJAY NAGDEV H.O. MEDICAL UNIT-I CHANDKA MEDICAL COLLEGE LARKANA
  • 2. Background
    • In 1962 nalidixic acid was discovered by George lesher during synthesis of chloroquine and was named as quinolone
    • Fluoroquinolones were derived by adding flourine atom in nalidixic acid.
  • 3.
    • Earlier quinolones were useful only for treatment of UTI.
    • Fluorinated derivatives achieve bactericidal levels in blood and tissues so they have improved antibacterial spectrum.
  • 4. MECHANISM OF ACTION
    • Fluroquinolones are bactericidal agents
    • They block bacterial DNA synthesis by inhibiting bacterial DNA gyrase and topoisomerase IV.
    • Inhibition of DNA gyrase prevents the relaxation of positively supercoiled DNA that is required for normal transcription and replication
  • 5. Cont….
    • Inhibition of topoisomeraseIV interferes with separation of replicated chromosomal DNA into the respective daughter cells during cell division.
    • They can enter cells easily via porins and are used to treat intracellular pathogens ( Legionella, pneumophila and Mycoplasma)
  • 6. RESISTANCE
    • Resistance is due to
    • one or more point mutations in the quinolone binding region of the target enzyme
    • OR to a change in the permeability of the organism
    • Resistance to one FQL confers cross resistance to all members of the class.
  • 7.
    • CLASSIFICATION
  • 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. Pharmacokinectics
    • Well absorbed orally with bioavailability 80-95% almost equal to i.v.
    • Half life 3-10 hours
    • Oral absorption impaired by divalent cations(Antacids containg Mg, Ca,or AL ).
    • Most of fluoroquinolones eleminated by renal mechanism so adjustment required in patients with creatinine clearance <50 ml/min.
    • Limited CSF penetration.
  • 10. Distribution
    • [Conc] > serum:
      • Prostate tissue
      • Stool
      • Bile
      • Lung
      • Kidneys
      • Neutrophils
      • Macrophages
    • [Conc] < serum:
      • Prostatic fluid
      • Bone
      • CSF
  • 11. Drug interactions Drugs increasing levels of FQL FQL increasing the levels of : Theophyline Antidepressants NSAIDS Imipramine corticosteroids Caffene Theophyline Warfarin (INR –monitored)
  • 12.  
  • 13.  
  • 14. Adverse effects.
    • Generally safe antibiotics
    • G.I.T -nausea,vomiting,diarrhea and antibiotic associated colitis have been reported.
    • CNS -confusion,insomnia,dizziness,anxiety,and seizures(displacement of GABA from its receptors).
    • CVS -torsade de pointes,prolonged QTc interval.
    • 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.)
  • 15. Cont.
    • Tendonitis and tendon rupture is rare but very serious.
    • Phototoxicity-avoid excesive sun exposure.
    • Leukopenia,eosinophilia (rare)
    • Mild elevation in transaminases (rare)
  • 16. Contraindication
    • Childrens (not absolute)
    • Pregnancy
    • Lactation
    • Epilepsy
    • QTc prolongation
  • 17.
    • Commonly used Fluoroquinolones
  • 18. Ciprofloxacin
    • 2 nd generation fluoroquinolone
    • Mainly effective against G –ve bacteria :
    • Enterobacteriacae H. influenzae M. catarrhalis
    • Campylobacter Pseudomonas N. gonorrheae
    • Intracellular pathogens
    • M. Tuberculosis Mycoplasma Chlamydia
    • Legionella Brucella
    • Not effective against G+ and anaerobes
  • 19. Clinical uses
    • 1.Urinary tract infections (G- bacteria)
    • 2. Osteomyelitis due to P. aeruginosa
    • 3. Gonorrhea
    • 4. Travellers’ diarrhea- ciprofloxacin commonly used
    • 5. Tuberculosis
    • 6. Prostatitis
    • 7. Community- acquired pneumoniae
    • 8. Diabetic foot infections ( P. aeruginosa )
    • 9.Anthrax
  • 20.
    • Usual duration is 7-14 days
    • Available forms
    • Brand name : ciproxin(bayer),cycin.
    Oral Parentral Opthalmic 100 mg 200 mg iv 3mg/ml solution 250 mg 400 mg iv 3.3mg/mg ointment 500 mg
  • 21. Levofloxacin
    • 3 rd generation fluoroquinolone
    • Spectrum: Gram-ve, Gram+ve (S. aureus including MRSA & S. pneumoniae) and Legionella pneumophila, atypical resp. pathogens,
    • Mycobacterium tuberculosis
    • Indications:
      • Chronic bronchitis and CAP
      • Nosocomial pneumonia
      • Intra-abdominal infections
  • 22. Cont.
      • Adverse reaction.
      • Blood glucose disturbances in DM patients
      • QTC prolongation, torsades de pointes, arrhythmias
      • Nausea, GI upset
      • Interstitial nephritis
  • 23.
    • Usual duration same 7-14 days
    • Available forms
    • Brand name:leflox,l-cyn,qumic
    Oral Parentral Opthalmic 100 mg 5 mg/ml iv 5mg/ml solution 250 mg 25 mg/ml iv 500mg
  • 24.