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![Distribution
[Conc] > serum:
Prostate tissue
Stool
Bile
Lung
Kidneys
Neutrophils
Macrophages
[Conc] < serum:
Prostatic fluid
Bone
CSF](https://image.slidesharecdn.com/fluroquinolones2110307004430phpapp01-1-160219065941/75/fluoroquinolones-medchem-oriental-college-of-pharmacy-22-2048.jpg)
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fluoroquinolones medchem- oriental college of pharmacy
This document provides information on fluoroquinolones, a class of broad-spectrum antibacterial drugs. It discusses the history and development of fluoroquinolones from nalidixic acid to newer generations with expanded spectra. The mechanisms of action targeting DNA gyrase and topoisomerase IV are described. Resistance development, pharmacokinetics, clinical uses, adverse effects and examples like ciprofloxacin and levofloxacin are summarized. The document is intended to guide readers on key aspects of fluoroquinolones.
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fluoroquinolones medchem- oriental college of pharmacy
- 1. BY: SONALI KANADE KAUSHIK.N.KUCHE RUCHA.J.KADMANE DIKSHA KANOJIYA GUIDEDBY : MR . AMJAD ALI ORIENTAL COLLEGE OF PHARMACY , SANPADA, NAVIMUMBAI.
- 2. DEFINITION: The fluoroquinolones area family of broad spectrum, systemic antibacterial agents that have been used widely as therapy of respiratory and urinary tract infections.
- 3. Background In 1962 nalidixicacid was discovered by George Lesher during synthesis of chloroquine and was named as Quinolone. Fluoroquinolones were derived by adding fluorine atom in nalidixic acid.
- 4. Earlier quinolones wereuseful only for treatment of UTI. Fluorinated derivatives achieve bactericidal levels in blood and tissues so they have improved antibacterial spectrum.
- 5. 1. SAFER TOUSE 2.HIGH POTENCY 3.NEW FLUOROQUINOLONES ARE BROAD IN SPECTRUM 4.DEEP PENETRATION IN TISSUES (but dose not cross BBB. Can enter the cell i.e intracellular organism) 5.GOOD ORAL ABSORPTION FLUOROQUINOLONES ARE FIVE STAR DRUGS !!!
- 6.
- 7. Generations Drugs Spectrum 1st (Quinolone) Nalidixic acidGram -ve but not Pseudomonas species 2nd Norfloxacin Ciprofloxacin Ofloxacin Gram -ve(including Pseudomonas species), some Gram+ (S. aureus) and some atypicals 3rd Levofloxacin Sparfloxacin Moxifloxacin Gatifloxacin Same as 2nd generation with extended Gram +ve and atypical coverage 4th *Trovafloxacin Same as 3rd generation with broad anaerobic coverage
- 8. Structural relativity offluoroquinolones
- 9.
- 10. ciprofloxacin Ofloxacin Norfloxacin Second generationfluoroquinolones
- 11.
- 12. Trovafloxacin Fourth generation offluoroquinolones
- 13. SYNTHESIS OF CIPROFLOXACIN USERETROSYNTHESIS TECHNIQUE IT WOULD MAKE YOUR LIFE EASY.. !
- 14.
- 15.
- 16. Topoisomerase II :to convert the +ve supercoiling to –ve supercoiling. There by allowing the process of replication or the allows the action of DNA helicase to proceed. Topoisomerase IV: to separate the entangled DNA so that its expression could be proceeded. MECHANISM OF ACTION
- 17. Fluoroquinolones blocks theligase action where in has no effect on endoneuclease action of the enzyme. Thus what the bacteria left with is fragments of DNA which cannot be expressed.
- 18. MECHANISM OF ACTION(cont..) Fluoroquinolones 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
- 19. Cont…. Inhibition of topoisomeraseIVinterferes 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)
- 20. RESISTANCE Resistance isdue 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.
- 21. Pharmacokinectics Well absorbed orallywith bioavailability 80-95% almost equal to IV Half life 3-10 hours Oral absorption impaired by divalent actions(Antacids containing Mg, Ca or Al ). Most of fluoroquinolones eliminated by renal mechanism so adjustment required in patients with creatinine clearance <50 ml/min. Limited CSF penetration.
- 22. Distribution [Conc] > serum: Prostatetissue Stool Bile Lung Kidneys Neutrophils Macrophages [Conc] < serum: Prostatic fluid Bone CSF
- 23. Drug interactions Drugs increasinglevels of FQL FQL increasing the levels of : Theophyline Antidepressants NSAIDS Imipramine corticosteroids Caffene Theophyline Warfarin (INR –monitored)
- 26. Adverse effects. Generally safeantibiotics 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.)
- 27. Cont. Tendonitis and tendonrupture is rare but very serious. Phototoxicity-avoid excesive sun exposure. Leukopenia,eosinophilia (rare) Mild elevation in transaminases (rare)
- 28.
- 29.
- 30. Ciprofloxacin 2nd generation fluoroquinolone Mainly effectiveagainst 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
- 31. Clinical uses 1.Urinary tractinfections (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
- 32. Usual duration is7-14 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
- 33. Levofloxacin 3rd 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
- 34. Cont. Adverse reaction. Blood glucosedisturbances in DM patients QTC prolongation, torsades de pointes, arrhythmias Nausea, GI upset Interstitial nephritis
- 35. Usual duration same7-14 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
- 36. REFERENCE:- http://www.DrNajeebLectures.com http://en.wikipedia.org/wiki/Quinolone Wilson andgisvolds textbook of Organic Medicinal and Pharmaceutical Chemistry, by JhonH.Block and Jhon M. Beale. Eleventh edition. Pgno 247-252. Foye’s principles of Medicinal chemistry, by Thomas L. lemke, David A williams.