POWERPOINT PRESENTATION ON QUINOLINE

IT CONTAINS BASIC INFORMATION THAT ANY PERSON NEED TO UNDERSTAND ANTIBIOTIC QUINOLINE.

1. PRESENTATIONON
QUINOLONES
PRESENTED BY:
AYESHA RUQSAR
M.PHARMACY STUDENT.

3. INTRODUCTION
Quinolonesarethesyntheticantimicrobialagentswhich
aredevelopedin1980’s.
Nalidixicacidwasthefirstquinoloneparentdrug
introducedin1960’safterthatintroductionof6-
fluorinated-4-quinolone(suchasciprofloxacinand
analoguescalledfluoroquinolones)tookplace
Fluroquinoloneswerehighpotent,expanded
spectrum,slowdevelopmentofresistance,bettertissue
penetrationandgoodtolerability.

4. CHEMISTRY
•FQ’s have a basic structure of 4 quinolone3 carboxylic acid
•The common feature of all
FQ’s is that they have a
–COOH group at position-3.
•The –COOH group a position
position 3 and –CO at position
4 increases hydrophobicity
therefore facilitates drug entry
into gram negative bacteria.

5. CHEMISTRY

6. CLASSIFICATION
NOTE: This classification is based on when drug was introduced whereas detailed study of drugs studied in later slides is
based on spectrum of activity.

7. MECHANISM OF ACTION
FQ’senterthebacterialcellsbypassive
diffusionthroughporinchannels.
Intracellularlyingram–vebacteria,thesedrug
inhibittheenzymeDNAgyraseandthus
preventreplicationofbacterialDNAduring
bacterialgrowthandreproduction.
Ingram+vebacteriatheyinhibittopoisomerase
IVandthusinterferewithseparationof
replicatedchromosomalDNAintothe
respectivedaughtercellduringcelldivision.

8. ItblocksbacterialDNAsynthesisby
InhibitionofbacterialDNAGyrase
InhibitionofTopoisomeraseIV
InhibitionofATPdependentDNAgyrase;whichnicks
doublestrandedDNA,introducesnegativesupercoilsand
thenresealsthenickedends.Thisisrequiredtoprevent
excessivepositivesupercoilingofDNAstrandswhen
theyseparatetopermitreplicationortranscription.
InhibitionofDNAgyrasealsopreventstherelaxationof
positivelysupercoiledDNA.
InhibitionofDNAnicking–closingenzymeresponsible
forDNAelongation,whichleadstobreakindouble
strandedDNA.
Mechanism of action for DNA gyrase

10. InhibitionoftopoisomeraseIV
interfereswiththeseparationof
replicatedchromosomalDNA
intorespectivedaughtercells
duringcelldivision.
Thecriticalimbalancein
cellularmetabolismresulting
fromtheinhibitionofenzymes
precipitatesasequenceof
cellulareventswhichmaylead
to:
1.Prematurecelldivision
2.Delayedcelldivision
3.Totalfailureofcelldivision
leading to
lysisofthecell
Mechanism of action for TOPOISOMERASE -IV

11. MECHANISMOFRESISTANCE
FQ’sareresistedduetochromosomalmutation
andproducingaDNAgyraseortopisomeraseIV
withreducedaffinity.
Duetoreducedpermeability.
increasedeffluxofthesedrugsacrossbacterial
membranes.
Increasingresistancehasbeenreportedamong
salmonella,pseudomonas,staphylococci,
gonococciandpneumococci.

12. QUINOLONEDRUG
NON FLUORINATED QUINOLONES
NALIDIXICACID
Nalidixicacidis4-quinolonederivativeandbactericidalinnatureandshoweffect
selectivelytogramnegativebacteria.
DOSE:0.5-1gmTDSorQID
PHARMACOKINETICS :
A:itiswellabsorbedorallyfromgastrointestinaltract.
D:proteinbindingcapacityishigh98%,plasmalifeis6-8hrs
M:itispartlymetabolizedbyliverandoneofitsmetaboliteisactive
E:itisrapidlyexcretedthroughurine
ADVERSEEFFECTS:headache,abdominalpain,photosensitivity,skinrashesetc.,.
DRUGINTERCTIONS:
caffeinereducesclearanceandprolonghalflife
Anticoagulanteffectofwarfarinareenhanced
THERAPEUTICUSES:
ItisusedinUTI
TotreatdiarrhoeacausedbyE.coli,salmonella,proteases

13. FLUORINATED COMPOUNDS
FIRST GENERATION FQ’S
CIPROFLOXACIN
Itistheprototypedrugfrom1
st
generationFQ’s
Itisusedhighlyagainstgram-veaswellsomegram+vebacteria
DOSE:500mgBIDfor7days.
PHARMACOKINETICS :
A:bioavailability(PO):50-85%
D:itiswidelydistributedthroughoutthebody,proteinboundis20-40%
M:itmetabolizeinliverbyenzymeinhibitorCYP1A2.
E:half-lifeis2-5hrsandisexcretedinurine(30-50%)feces(15-43%)
ADR’S:nausea,abdominalpain,hallucination,anemia,rashes,blurrredvision.
DRUGINTERACTIONS:
Aluminiumhydroxidedecreasesserumconc.Ofciprofloxacin
Ciprofloxacinincreaseseffectsofmetforminbypharmacodynamicsynergism.
CONTAINDICATIONS:Itiscontaindicatedininfantsandpregnantwoman's
THERAPEUTICUSES:UTI,thypoid,STD’S,respiratoryinfections,TB

14. SECOND GENERATON FQ’S
LEVOFLOXACIN
ITisl-isomerofolfloxacinbutismoreactivethanciprofloxacin.They
aremoreactivetogram+vethangram–vebacteriasandcocci
DOSE:500mgODfor10-14days.
PHARMACOKINETICS :
A:Wellabsorbed,bioavailabilityis99%&peakserumtimeis1-2hrs
D:CSFconc.isupto15%
M:limitedmetabolisminhumans
E:87%drugisrecoveredasunchangeddruginurinewithin48hrs
ADR’s:nausea,headache,insomnia,chestpain,convulsions,acuteRF
DRUGINTERACTIONS:
Ondansetrone&levofloxacinbothincreasesQTcinterval.
Levofloxacinincreaseseffectofdigoxinbyalteringintestinalflora.
CONTRAINDICATIONS:
Patientwithhistoryofmyastheniagravis
Withrenalimpairedpatient.
USES:itisusedinentericfever,softtissueinfections,pneumoniaand
chronicbronchitis

15. THIRDGENERATION FQ’S
GATIFLOXACIN
ITisbactericidalinnatureandhasgoodactivityagainstanaerobes,gram+vebacteria
(cocci)andatypicalrespiratorypathogen.
DOSE:400mgOD
PHARMACOKINETICS :
A:oralbioavailabilityis96%asdrugisrapidlyabsorbedfromgastrointestinaltract.
D:proteinbindingcapacityispoor(20%)
M:itmetabolisesinliver
E:itiseliminatedthroughfaecesandurine.
CONTRAINDICATIONS:
Itiscontaindicatedinhypokalemiapatients&heartpatients.
DRUGINTERACTIONS:
itchangesbloodglucoselevelsocautiousalongwithmetformin.
Itcannotbegivenalongwithantidepressentsatleastagapof2-6hrsisrequired.
USES:itisusedintreatmentofacutebactericidalexacerbation,pneumonia,upperand
lowerrespiratorytrackinfections.
ADR:itcausestachycardia,photosensitvityetc.,.

16. FOURTHGENERATIONFQ’S
MOXIFLOXACIN
ItissyntheticFQ’sshowenhancedagainstgram+veorganism,
gram–vebacteriaandanaerobes
DOSE:400mgOD
PHARMACOKINETICS :
A:Bioavailability90%itiswellabsorbed
D:itis50%proteinbound
M:itismetabolizedbyliverviaglucuronide&sulfateconjugation
E:halflifeis12hrs&excretedbybothurine&faeces
DRUGINTERACTIONS:
Desipramine&moxifloxacinbothincreasesQTclevels.
Moxifloxacinincreaseseffectofantidepressants.
CONTRAINDICATIONS:itiscontraindicatedinseizurepatients
andindividualwithproarrhythmicdrugs.
ADR:headache,nauseaetc
USES:itisusedinpneumonia,TB,bronchitis,sinusitis.

17. COMMONADVERSEEFFECTSOFQUINOLONES
Neurologicaleffects:headache,drowsiness,rarely
seizers,anxiety,depressionetc.,.
Gastrointestinalmanifestation:nausea,vomiting,
stomachacheetc.,.
Hypersensitivityreactions:skinrashes,photosensitivity,
swellingoflipsetc.,.
Tendonitisandtendonrutures.
Itiscontraindicatedinchildrenandpregnantwomen's.

18. COMMONINTERACTIONS OFQUINOLONES
1. NSAIDs :
Enhance the CNS toxicity of quinolones
2. Theophylline, Caffeine or Warfirine
Plasma concentration is increased by Ciprofloxacin
3. Antacid or Iron salts
Reduce the absorption of quinolones

19. GENERALUSEOFQUINOLONES
1.RTI(RespiratoryTractInfection):
EMPYEMA:Thecollectionofpusinacavityofthebody,
especiallyinthepleuralcavity(theareabetweenthelungsandthe
innersurfaceofthechestwall)
PNEUMONIA:Infectionofthelungsthatcausedbybacteria,
viruses,fungiorparasites
LUNGABSCESS:Bacterialinfectionthatoccursinthelung
tissuecausingtissuetodieandpustocollectinthatspace
2.MENINGITIS:Inflammationoftheliningofthebrainandspinal
cord
3.UTI(UrinaryTractInfection):
PYELONEPHRITIS:Atypeofurinarytractinfection(UTI)that
affectsoneorbothkidneyscausedbyabacteriummainly
Escherichiacoliorvirusinfection.Itcausesthekidneystoswell
andmaypermanentlydamagethem.

20. 4.GIT(GastroIntestinalTract)infection:
ENTERICFEVER:Apotentiallyfatalmultisystemicillness
causedprimarilybySalmonellaspecies
BACTERIALDIARRHOEA :CausedbyCampylobacter,
salmonellae,andshigellaorganisms
5.Skin&softtissueinfections:
INFECTEDULCERS:Shallowwoundthatdevelopsonthe
skin
INFECTEDBURNS:Redcolouredandwarmtotouchdueto
aninfection.
6.TUBERCULOSIS:Infectiousbacterialdiseasecharacterizedby
thegrowthofnodules(tubercles)inthetissues,especiallythe
lungs
7.CONJUCTIVITIS:Inflammationoftheoutermostlayerofthe
whitepartoftheeyeandtheinnersurfaceoftheeyelid
8.Itisusedinvaginalaswellasmanyprostateinfections.

21. THANKYOU