FLUOROQUINOLONES the separation of interlinked daughter chromosomes i.e.

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Last updated: May 14, 2019

FLUOROQUINOLONESThefluoroquinolones are systemic antibacterial agents, from a family of broadspectrum, used widely as therapy of urinary and respiratory tract infections29. Fluoroquinolones target two enzyme, i.e.

DNA gyrase and topoisomeraseIV, in the bacteria’s cell; both are essential targets for bacterial DNAreplication. 23Microbiology:A wide range of aerobicgram-positive and gram-negative organisms are sensitive against flouroquinolones.Gram-positive coverage includes:1.      Penicillinase2.      non-penicillinaseproducing Staphylococci, Streptococcus pneumoniae and viridans, 3.      Enterococcusfaecalis,4.

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       Listeria monocytogenes,5.      Nocardiaspecies.  Gram negative coverage includes: 1.

      Neisseria meningitides2.      Gonorrhoeae3.      Haemophilusinfluenzae, 4.      Enterobacteriaceaespecies, 5.

      Pseudomonasaeruginosa6.      Vibriospecies. 30Types:Older:·        Ciprofloxacin·        ofloxacinNewer:·        levofloxacin·        sparfloxacin·        grepafloxacin·        trovafloxacin. ·        gatifloxacin·        moxifloxacin Mechanism of action: Introduction of negative super helical twists into DNA is onlydone by bacterial enzyme DNA gyrase 24. For initiation of DNAreplication, negatively super twisted DNA is important. DNA replication are alsofacilitates by DNA gyrase DNA gyrase which removing twists of positive super helicalthat accumulate ahead of the replication fork or as a result of thetranscription of certain genes 24, 25. The terminal stages of DNAreplication is acted by Topoisomerase IV, allowing for the separation ofinterlinked daughter chromosomes i.

e. decatenation so that daughter cells canbe segregated 26, 27. Inhibition of these enzymes by Fluoroquinolonesis done by stabilizing either the DNA-topoisomerase IV complex or the DNA-DNAgyrase complex 22. Movement of the replication fork is blocked bythe stabilized DNA-DNA gyrase complex, causing formerly reversible DNA-enzymecomplexes that become irreversible 28.

Damage to DNA and thebreakage of the generation of DNA-strand then a set of events trigger, as yet definedpoorly, the rapid inhibition of DNA synthesis are followed and eventual celldeath is the result23, 25 .The fluoroquinolones are interacted with two bacterialtargets, topoisomerase IV  and therelated enzymes DNA gyrase, DNA replication are involved by both enzymes, form enzymescomplexes with DNA, movement of the DNA-replication fork are blocked by that complexesand causes inhibition of  DNAreplication. Indications:Indication of flouroquinolones includes 31bacterialbronchitis, pneumonia, sinusitis, urinary tractinfections, septicemia, intraabdominal infections, joint and bone infections, softtissue, skin infections, typhoid fever, bacterial gastroenteritis, urethral andgynecological infections, pelvic inflammatory disease and several otherinfectious conditions.Pharmacokinetics:1.       Common FeaturesThe fluoroquinolones’ pharmacokinetic features have beensummarised in recent times.

19 They oral absorption andbioavailability are moderate to excellent, marginally affected by food.  Generally rapid absorption, within 1 to 2hours, peak plasma concentrations (Cmax) achieved. divalent cations, includingAl+++, Mg++, Ca++ and Fe++ are frequently found in antacids and othermedications as well as in dairy products reduce the absorption,.13 Most drugshave volumes of distribution exceed 1.5 L/kg, consistent with significantdistribution into tissues and cells while moderate clearance and eliminationhalf-lives (4 to 10 hours).2.

       Variable FeaturesThe variation of predominant route of elimination is widelybetween fluoroquinolones. The l-isomer of Ofloxacin, levofloxacin,lomefloxacin, rufloxacin and gatifloxacin have minimal metabolism (<10%) andpredominant renal excretion. In contrast pefloxacin, nalidixic acid, grepafloxacinand sparfloxacin undergo extensive hepatic metabolism (>35%). The otherdrugs undergo modest metabolism but as well as have significant levels of renalexcretion. To some extent Protein binding also varies, the degree of binding withnorfloxacin, gatifloxacin and lomefloxacin having the lowest, and rufloxacin, clinafloxacinand trovafloxacin the highest. 20-223.

       Tissue PenetrationFor most fluoroquinolones, tissue concentrations are usuallyhigher than plasma concentrations. This tissue penetration is not related tolipid solubility. In contrast, fluoroquinolones have relatively poor CSFpenetration into uninflamed meninges, but at least 4 agents ? ciprofloxacin,pefloxacin, ofloxacin and trovafloxacin ? are known to penetrate to a moderateextent in the presence of inflammation. 19Side effects:The fluoroquinolones’ common side effects are:·        Disturbancesof gastrointestine·        skinrash·        Allergicreactions. ·        headachesMore severe side effects but less common include: ·        QTprolongation·        tendonrupture·        Hallucinations·        Seizures·        Photosensitivity·        Angioedema.32 

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