Chemotherapy for BDS and Pharmacy students-April24.pdf

useful for BDS Pharmacy students

1. GENERAL AND DENTAL
PHARMACOLOGY AND THERAPEUTICS
PART-B
CHEMOTHERAPY
Dr Nishi Prakash Jain
Principal
RKDF College of Pharmacy
SRK University Bhopal
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2. SYLLABUS
•Antimicrobialagents(againstBacteria,anaerobicinfection,fungi,
virusandbroadspectrum),InfectionmanagementinDentistry,
PharmacotherapyofTuberculosis,Leprosyandchemotherapyof
malignancyingeneral,Implicationofchemotherapyinclinical
Dentistry.
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3. Microbiology
•Microbiologyisthestudyofmicroscopicorganisms,including
bacteria,viruses,fungi,andparasites,andtheirinteractionswith
humans.Indentistry,understandingmicrobiologyisessentialfor
preventingandmanagingoralinfections,promotingoralhealth,and
ensuringthesuccessofdentalprocedures.
•Bacteriaarethemostabundantmicroorganismsinthemouth,with
over700differentspeciesresidingintheoralmicrobiome.
Understandingthecharacteristicsandbehaviorsofthese
microorganismsiscrucialfordiagnosingandtreatingoralinfections.
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4. •OralMicrobiome:Theoralcavityharborsacomplexecosystemof
microorganisms,collectivelyknownastheoralmicrobiome.These
microorganismsplayavitalroleinmaintainingoralhealthbyparticipating
inprocessessuchasdigestion,immuneregulation,andprotectionagainst
pathogens.However,dysbiosis,animbalanceintheoralmicrobiome,can
leadtooraldiseasessuchasdentalcaries,periodontaldisease,andoral
candidiasis.
•Severalmicroorganismsareimplicatedinoraldiseases.Streptococcus
mutans,forexample,isaprimarycausativeagentofdentalcaries,while
Porphyromonasgingivalisisassociatedwithperiodontaldisease.
•Dentalproceduresinvolveclosecontactwithpatients'oraltissuesand
fluids,increasingtheriskofcross-contaminationandinfection
transmission.Knowledgeofmicrobiologyisessentialforimplementing
effectiveinfectioncontrolmeasures,includingpropersterilizationof
instruments,useofpersonalprotectiveequipment,andadherenceto
standardprecautions.
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5. ANTIMICROBIAL AGENTS
•ThewordantimicrobialwasderivedfromtheGreekwordsanti(against),
micro(little)andbios(life)andreferstoallagentsthatactagainstmicrobial
organisms.Antimicrobialagentisageneraltermthatismainlyconcerned
withAntibiotics,Antibacterials,Antifungals,AntiviralsAndAntiprotozoans.
•Antimicrobialagentsaredrugs,chemicalsorothersubstancesthatare
capableofactingbytwomodeseitherkill(microbiocidal)orslowthe
growthofmicrobes(microbiostatic).
•Antimicrobialmedicinescanbeclassifiedaccordingtothemicroorganisms
theyactprimarilyagainst.Forexample,antibacterialsareused
againstbacteriaandantifungalsareusedagainstfungi.
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6. BACTERIA
•Bacteriaareunicellularorganismsbelongingtothe
prokaryoticgroupwheretheorganismslackafew
organellesandatruenucleus”.Bacteriacanbe
classifiedintovariouscategoriesbasedontheir
featuresandcharacteristics.Theclassificationof
bacteriaismainlybasedonthefollowing:
•Shape
•Composition of the cell wall
•Mode of respiration
Mode of nutrition
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7. Classification of bacteria based on Shape
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8. Classification of bacteria based on the Composition
of the Cell Wall
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9. DEFINITIONS
Chemotherapy:Chemotherapyreferstothetreatmentofdisease,
especiallycancer,usingchemicalsubstances.Inthecontextofcancer
treatment,chemotherapytypicallyinvolvestheuseofcytotoxicdrugsor
medicationstodestroycancercellsorimpedetheirgrowthand
proliferation.Chemotherapycanbeadministeredorally,intravenously,
orviaotherroutesandisoftenusedincombinationwithother
treatmentssuchassurgeryandradiationtherapy.
AntimicrobialAgents:Antimicrobialagentsaresubstancesthathave
theabilitytokillorinhibitthegrowthofmicroorganisms,including
bacteria,viruses,fungi,andparasites.Theseagentsareusedtotreat
infectionscausedbyvariousmicroorganismsandcanincludeantibiotics,
antiviraldrugs,antifungalagents,andantiparasiticmedications.
Antimicrobialagentsworkbytargetingspecificcomponentsor
processesessentialforthesurvivalandreplicationofmicroorganisms,
thushelpingtoeradicatetheinfection.
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10. •Antibiotics:Antibioticsareatypeofantimicrobialagentspecificallyused
totreatbacterialinfections.Theyarecompoundsproducedby
microorganisms(suchasbacteriaandfungi)orsynthesizedchemically
thathavetheabilitytoinhibitthegrowthofbacteriaorkillthem
outright.Antibioticsworkbytargetingbacterialcellstructuresor
metabolicprocesses,suchascellwallsynthesis,proteinsynthesis,
nucleicacidsynthesis,ormetabolicpathways.Examplesofantibiotics
includepenicillins,cephalosporins,tetracyclines,macrolides,and
fluoroquinolones.
•Antibacterials:Antibacterialsaresubstancesthatspecificallytarget
bacteriaandareusedtotreatbacterialinfections.Theterm
"antibacterial"isoftenusedinterchangeablywith"antibiotic,"although
technicallyantibioticsrefertoasubsetofantibacterialagents.
Antibacterialscanincludevariousclassesofdrugs,suchasantibiotics,as
wellasothertypesofantimicrobialagentsthatspecificallytarget
bacteria.Theseagentsworkbydisruptingbacterialcellstructuresor
processes,leadingtobacterialcelldeathorinhibitionofgrowth.
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11. MECHANISMOFACTIONOFANTIMICROBIALDRUGS
Antimicrobialdrugsexerttheireffectsthroughvariousmechanismsof
action,targetingspecificcomponentsorprocessesessentialforthe
survivalandreplicationofmicroorganisms.Herearesomecommon
mechanismsofaction:
1.InhibitionofCellWallSynthesis:
•Manyantimicrobialdrugs,suchasbeta-lactamantibiotics(e.g.,penicillins,
cephalosporins)andglycopeptides(e.g.,vancomycin),targetbacterialcellwall
synthesis.
•Theyinhibittheactivityofenzymesinvolvedinpeptidoglycanbiosynthesis,
disruptingcellwallintegrityandleadingtocelllysis.
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12. 2.InhibitionofProteinSynthesis:
•Antimicrobialagentscaninterferewithbacterialproteinsynthesisbytargeting
eitherthe30Sor50Sribosomalsubunits.
•Drugslikeaminoglycosides(e.g.,gentamicin),tetracyclines(e.g.,doxycycline),
macrolides(e.g.,erythromycin),andoxazolidinones(e.g.,linezolid)bindto
ribosomalsubunits,preventingtranslationorcausingfaultyproteinsynthesis.
3.InhibitionofNucleicAcidSynthesis:
•Someantimicrobialdrugsinterferewiththesynthesisorfunctionofnucleicacids
(DNAorRNA)inmicroorganisms.
•Fluoroquinolones(e.g.,ciprofloxacin)inhibitbacterialDNAgyraseor
topoisomeraseIV,enzymesinvolvedinDNAreplicationandrepair,leadingto
DNAdamageandcelldeath.
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13. 3.DisruptionofCellMembraneIntegrity:
•Certainantimicrobialagentsdisrupttheintegrityofbacterialcellmembranes,
causingleakageofcellularcontentsandcelldeath.
•Polymyxins(e.g.,polymyxinB,colistin)bindtothebacterialcellmembrane,
disruptingitsstructureandpermeability,particularlyinGram-negativebacteria.
4.InhibitionofMetabolicPathways:
•Antimicrobialdrugscaninhibitspecificmetabolicpathwaysessentialfor
microbialgrowthandsurvival.
•Sulfonamides(e.g.,sulfamethoxazole)andtrimethopriminhibitbacterialfolate
synthesis,interferingwithnucleicacidandproteinsynthesis.
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14. 6.DisruptionofMicrobialDNA/RNAFunction:
•SomeantimicrobialagentstargetmicrobialDNAorRNAdirectly,interferingwith
essentialprocessesliketranscriptionorreplication.
•RifampininhibitsbacterialRNApolymerase,preventingtranscriptionofbacterial
genes.
7.InhibitionofEssentialEnzymes:
•Certainantimicrobialdrugsinhibitspecificenzymesessentialformicrobial
growthandmetabolism.
•Proteaseinhibitors,suchasthoseusedinantiviraltherapy(e.g.,ritonavirfor
HIV),blocktheactivityofviralproteasesrequiredforviralreplication.
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16. CLASSIFICATION OF ANTIMICROBIALS ON THE
CHEMICAL STRUCTURE
1.Beta-LactamAntibiotics:Penicillins(PenicillinG,amoxicillin),
Cephalosporins(Cephalexin,Ceftriaxone),carbapenems(Imipenem,
meropenem),andmonobactams(Aztreonam).
2.Macrolides:Erythromycin,Azithromycin,AndClarithromycin.
3.Tetracyclines:Doxycycline,Minocycline,AndTetracycline.
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17. 4.Fluoroquinolones: Ciprofloxacin, levofloxacin, and moxifloxacin.
5.Glycopeptides: Vancomycin And Teicoplanin.
6.Aminoglycosides: Gentamicin, amikacin, tobramycin and streptomycin.
7.Sulfonamides: Sulfamethoxazole and sulfadiazine.
8.Oxazolidinones: Linezolid And Tedizolid.
9.Diaminopyrimidines: Trimethoprim, Pyrimethamine
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18. 10. Lincosamide: Lincomycin,Clindamycin
11. Polypeptides Antibiotics: Polymoxin-B,Colistitin.
12.Nitrofuran Derivatives: Nitrofurantoin, Furazolidine.
13.Nitroimidazoles: Metronidazole, Tinidazole
14. Nicotinic Acid Derivatives: Isoniazide, Pyrazinamide,
15. Polyene Antibiotics: Nystatin, Amphoteracin-B, Hamycin
16.Azole Derivatives: Miconazole, Clotrimazole, Fluconazole,
17. OTHERS : Griseofulvin, Sod. Fusidate, Ethambutol, Rifampcin,
Cycloserin
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19. CLASSIFICATION OF ANTIMICROBIAL AGENTS
FOR BACTERIA
1.Beta-lactam antibiotics (e.g., penicillins, cephalosporins)
2.Macrolides (e.g., erythromycin, azithromycin)
3.Tetracyclines (e.g., doxycycline, tetracycline)
4.Fluoroquinolones (e.g., ciprofloxacin, levofloxacin)
5.Aminoglycosides (e.g., gentamicin, amikacin)
6.Glycopeptides (e.g., vancomycin)
7.Sulfonamides (e.g., sulfamethoxazole)
8.Oxazolidinones (e.g., linezolid)
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20. Beta-lactam antibiotics
•Beta-lactamantibioticsareaclassof
antibioticscharacterizedbyaβ-lactamringin
theirmolecularstructure.Thisringiscrucial
fortheirantibioticactivityasitinhibitsthe
synthesisofthebacterialcellwall,leadingto
bacterialcelldeath.Beta-lactamantibiotics
areamongthemostwidelyusedantibiotics
duetotheireffectivenessagainstabroad
spectrumofbacteria.
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21. Penicillins
•Penicillinsareaclassofbeta-lactamantibioticsderivedfromthe
fungusPenicillium.Theyarecharacterizedbythepresenceofabeta-
lactamringintheirchemicalstructure,whichisessentialfortheir
antimicrobialactivity.Penicillinsworkbyinhibitingthesynthesisof
bacterialcellwalls,leadingtobacterialcelldeath.
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22. Penicillinscanbeclassifiedintoseveralsubclassesbasedontheir
spectrumofactivityandchemicalstructure.
NATURALPENICILLINS:Examples:PenicillinG
(benzylpenicillin),PenicillinV(phenoxymethylpenicillin)
AMINOPENICILLINS:Examples:Ampicillin,Amoxicillin
ANTISTAPHYLOCOCCALPENICILLINS:Examples:Methicillin,
Oxacillin,Cloxacillin,Dicloxacillin
EXTENDED-SPECTRUMPENICILLINS:Examples:Carbenicillin,
Ticarcillin,Piperacillin
COMBINATIONPENICILLINS:(Amoxicillin/ClavulanicAcid),
(Ticarcillin/ClavulanicAcid),(Ampicillin/Sulbactam).
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23. Mode of action of Penicillins
a.InhibitionofCellWallSynthesis:Bacterialcellshavearigid
cellwallthatmaintainstheirshapeandprotectsthemfrom
environmentalstresses.Thiscellwallisprimarilycomposedof
peptidoglycan,acomplexpolymer.Penicillinsworkbyinhibiting
theenzymetranspeptidase,alsoknownaspenicillin-binding
proteins(PBPs),whichareresponsibleforcross-linkingthe
peptidoglycanstrandsduringcellwallsynthesis.
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24. b.FormationofInactiveEnzyme-DrugComplex:Penicillinshaveabeta-
lactamringintheirmolecularstructure.ThisringresemblestheD-Ala-D-
Alaportionofthepeptidoglycanprecursor.Whenabacteriumattempts
toincorporatethepenicillinmoleculeintoitscellwallduringsynthesis,
thebeta-lactamringirreversiblybindstotheactivesiteofPBPs.This
bindingpreventsthetranspeptidaseenzymefromcross-linkingthe
peptidoglycanstrandsproperly.
C.WeakeningandLysisoftheCellWall:Asaresultoftranspeptidase
inhibition,thebacterialcellwallbecomesstructurallyweakandunableto
withstandtheosmoticpressureinsidethecell.Consequently,water
entersthecell,causingittoswellandeventuallylyse(burst).Thislysis
leadstobacterialcelldeath.
d.SelectiveToxicity:Oneofthekeyfeaturesofpenicillinsistheirselective
toxicitytowardsbacteria.Thisselectivityarisesbecausebacterialcell
wallshavePBPsthatarespecifictargetsforpenicillins
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25. AMOXICILLIN
Amoxicillinisawidelyusedantibioticbelongingtothebeta-lactam
class,specificallyapenicillinderivative.
MechanismofAction:
Amoxicillininhibitsthetranspeptidaseenzymethatcatalyzesthefinal
stepinbacterialcellwallsynthesis.BybindingtoPBPs,particularly
PBP-1A,PBP-1B,andPBP-2,itdisruptsthecross-linkingof
peptidoglycanchains,weakeningthebacterialcellwallstructure.This
interferencewithcellwallsynthesisleadstobacterialcelldeathby
osmoticlysis.
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26. •PHARMACOKINETICS
•Absorption:Amoxicillinisabsorbedorally,withgoodandrapidabsorption
fromthegastrointestinaltract.Itsabsorptionisnotsignificantlyaffectedby
food.
•Distribution:Itdistributeswidelyintovarioustissuesandbodyfluids,
includingthelungs,middleear,sinuses,skin,softtissues,andgenitourinary
tract.
•Metabolism:Itundergoesminimalmetabolismandisprimarilyexcreted
unchangedviathekidneys.
•Elimination:Theeliminationhalf-lifeofamoxicillinistypicallyaround1hour
inadults,butthismayvarybasedonfactorssuchasrenalfunctionand
dose.
•SPECTRUMOFACTIVITY
•AmoxicillinhasabroadspectrumofactivityagainstmanyGram-positiveand
Gram-negativebacteria.
•ItiseffectiveagainstvariousstrainsofStreptococcuspneumoniae,
Streptococcuspyogenes,Haemophilusinfluenzae,Moraxellacatarrhalis,
Escherichiacoli,Proteusmirabilis,Salmonella,andsomestrainsof
Staphylococcusaureusthataresusceptibletopenicillinase.
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27. DOSE (ORAL)
Mild to moderate infections
•500 mg PO q12hr or 250 mg PO q8hr for 10-14 days
Severe infections
•875 mg PO q12hr or 500 mg PO q8hr for 10-14 days
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28. INDICATION
•Amoxicilliniscommonlyprescribedforvariousbacterialinfections,
includingrespiratorytractinfections(suchasotitismedia,sinusitis,
andpneumonia),urinarytractinfections,skinandsofttissue
infections,dentalinfections,andsomegastrointestinalinfections.
•Itisoftenusedincombinationwithotherdrugs,suchasclavulanic
acid(informulationslikeamoxicillin/clavulanate),toextendits
spectrumofactivityandovercomebacterialresistance.
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29. Resistance:
•Bacteriacandevelopresistancetoamoxicillinthroughvarious
mechanisms,includingproductionofbeta-lactamases(enzymesthat
degradebeta-lactamantibiotics),alterationsinPBPsreducingtheir
affinityforthedrug,andeffluxpumpsthatremovetheantibiotic
fromthebacterialcell.
•Combinationtherapieswithbeta-lactamaseinhibitorslikeclavulanic
acidcanhelpovercomesomeformsofresistance.
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30. Adverse Effects
•Commonadverseeffectsincludegastrointestinaldisturbancessuch
asnausea,vomiting,diarrhea,andabdominalpain.
•Allergicreactions,rangingfrommildskinrashestosevere
anaphylaxis,canoccur,particularlyinpatientswithahistoryof
penicillinallergy.
•Prolongeduseofamoxicillinmayleadtothedevelopmentof
antibiotic-resistantbacterialstrainsorovergrowthofnon-susceptible
organismslikeClostridiumdifficile,causingpseudomembranous
colitis.
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31. CEPHALOSPORINS
Cephalosporins are a class of antibiotics widely used in clinical
practice to treat bacterial infections.
Classification of Cephalosporins:
1.FirstGenerationCephalosporins:Examples:Cefazolin,
Cephalexin,Cefadroxil.
2.Second Generation Cephalosporins: Examples: Cefuroxime,
Cefaclor, Cefoxitin.
3.Third Generation Cephalosporins: Examples: Ceftriaxone,
Cefotaxime, Ceftazidime.
4.Fourth Generation Cephalosporins: Example: Cefepime.
5.Fifth Generation Cephalosporins: Example: Ceftaroline.
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32. MODE OF ACTION OF CEPHALOSPORINS
Likepenicillins,cephalosporinsdisruptthesynthesisof
peptidoglycan,avitalcomponentofbacterialcellwalls.Theyachieve
thisbybindingtoandinhibitingtheactivityofenzymescalled
Penicillin-bindingProteins(PBPs),whichareinvolvedinthecross-
linkingofpeptidoglycanstrandsduringcellwallsynthesis.Withouta
properlyformedcellwall,bacteriabecomestructurallyweakand
susceptibletoosmoticlysis,leadingtocelldeath.
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33. General Indications of Cephalosporins
Cephalosporinantibioticsareagroupofbroad-spectrumantibioticsusedto
treatawiderangeofbacterialinfections.Theyareeffectiveagainstboth
Gram-positiveandGram-negativebacteria.Thegeneralindicationsfor
cephalosporinantibioticsinclude:
•RespiratoryTractInfections:Cephalosporinsarecommonlyusedtotreat
respiratorytractinfectionssuchaspneumonia,bronchitis,andsinusitis
causedbysusceptiblebacteria.
•SkinandSoftTissueInfections:Cephalosporinsareeffectiveagainstbacterial
skininfections,includingcellulitis,impetigo,andwoundinfections.
•UrinaryTractInfections(UTIs):Cephalosporinsareoftenprescribedfor
uncomplicatedurinarytractinfectionscausedbysusceptiblebacteria,suchas
Escherichiacoli.
•SurgicalProphylaxis:Cephalosporinsarecommonlyusedasprophylactic
antibioticstopreventsurgicalsiteinfectionsbeforecertainsurgical
procedures.
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34. •Meningitis:Certaincephalosporins,particularlythird-generation
cephalosporinslikeceftriaxone,areeffectiveintreatingbacterial
meningitiscausedbyorganismssuchasStreptococcuspneumoniae,
Neisseriameningitidis,andHaemophilusinfluenzae.
•Intra-abdominalInfections:Cephalosporinsmaybeusedtotreatintra-
abdominalinfections,includingperitonitisandabdominalabscesses,in
combinationwithotherantibiotics.
•BoneandJointInfections:Cephalosporinsaresometimesusedtotreat
boneandjointinfections,includingosteomyelitisandsepticarthritis.
•GynecologicalInfections:Cephalosporinsmaybeprescribedtotreat
gynecologicalinfectionssuchaspelvicinflammatorydisease(PID)
causedbysusceptibleorganisms.
•SepticemiaandBacteremia:Cephalosporinsareusedinthetreatment
ofsepticemiaandbacteremiacausedbysusceptiblebacteria.
•OtherInfections:Cephalosporinsmayalsobeusedtotreatother
infectionssuchasotitismedia,endocarditis,andcertainsexually
transmittedinfections(STIs)causedbysusceptiblebacteria.
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35. INDICATIONS OF CEPHALOSPORIN IN DENTISTRY
•Prophylaxis for Dental Procedures
•Treatment of Odontogenic Infections
•Management of Oral and Maxillofacial Infections
•Adjunctive Therapy for Periodontal Disease
•Treatment of Acute Necrotizing Ulcerative Gingivitis (ANUG)
•Prevention and Treatment of Infections Following Oral Surgery
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36. General ADR of Cephalosporins
•HypersensitivityReactions:
•GastrointestinalDisturbances
•Superinfections:Cephalosporinusecandisruptthenormalbalanceof
microorganismsintheoralcavity,potentiallyleadingtosecondaryinfections
suchasoralthrush(candidiasis)orantibiotic-associateddiarrheacausedby
Clostridiumdifficile.
•Hepatotoxicity:Rarely,cephalosporinantibioticsmaycauseliverdamage,
manifestingaselevatedliverenzymes,jaundice,orhepatitis.Dentistsshould
monitorliverfunctioninpatientsreceivingprolongedcoursesof
cephalosporins,especiallythosewithpre-existingliverconditions.
•RenalImpairment:Certaincephalosporins,particularlythoseeliminatedby
renalexcretion,cancausenephrotoxicityinsusceptibleindividuals.Dentists
shouldusecautionwhenprescribingcephalosporinstopatientswithrenal
impairmentandadjustdosagesaccordingly.
•HematologicEffects:Cephalosporinantibioticsmayrarelycause
hematologicabnormalitiessuchasleukopenia,thrombocytopenia,or
hemolyticanemia.Dentistsshouldbeawareofthesepotentialeffectsand
monitorbloodcountsinpatientsreceivingprolongedcephalosporintherapy.
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37. DOSE OF SOME COMMON CEPHALOSPORIN
•Cephalexin(Nufex):
•For most infections: 250 mg to 500 mg orally every 6 hours, or 500 mg to 1,000 mg orally
every 12 hours.
•Severe infections: Up to 4 grams daily in divided doses.
•Cefuroxime:
•For mild to moderate infections: 250 mg to 500 mg orally every 12 hours.
•For severe infections: Up to 1,000 mg orally every 8 hours.
•Ceftriaxone:
•For most infections: 1 gram to 2 grams intravenously or intramuscularly once daily.
•Gonorrhea: Single dose of 250 mg intramuscularly.
•Cefixime:
•For most infections: 400 mg orally once daily or divided into two doses.
•Cefdinir:
•For most infections: 300 mg orally every 12 hours or 600 mg once daily.
•Cefepime:
•For moderate to severe infections: 1 gram to 2 grams intravenously or intramuscularly every
8 to 12 hours.
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38. CONTRAINDICATION of CEPHALOSPORIN
•Cephalosporinantibioticsaregenerallywell-tolerated,butlikeall
medications,theycanhavecontraindicationsandprecautions.Here
aresomecontraindicationsforcephalosporinantibiotics:
•AllergyorHypersensitivity:
•Cross-Allergies
•HistoryofSevereGastrointestinalDisease
•RenalImpairment
•BleedingDisorders
•NeonateswithHyperbilirubinemia
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39. MACROLIDES
Macrolidesareaclassofantibioticsthatinhibitbacterial
proteinsynthesisbybindingtothe50Ssubunitofthebacterial
ribosome.
Erythromycin: This was the first Macrolides discovered and is the
prototype of the class. It's effective against a broad spectrum of
bacteria but has some limitations due to its poor acid stability and
gastrointestinal side effects.
Clarithromycin: This is a derivative of erythromycin with improved
acid stability and a broader spectrum of activity.
Azithromycin: Azithromycin has a similar spectrum of activity to
clarithromycin but has the advantage of a longer half-life, allowing for
once-daily dosing. It is often used to treat respiratory tract infections,
sexually transmitted infections, and certain bacterial gastrointestinal
infections.
Spiramycin: Spiramycin is mainly used for its activity against Gram-
positive bacteria and some anaerobic bacteria. It's commonly used for
treating toxoplasmosis and certain other parasitic infections during
pregnancy.
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40. MOA of MACROLIDES
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41. Macrolidesinhibitbacterialproteinsynthesis.The
mechanismofactionofMacrolidesrevolvesaroundtheir
abilitytobindthebacterial50Sribosomalsubunitcausingthe
cessationofbacterialproteinsynthesis.Onceitbinds,thedrug
preventsthetranslationofmRNA,specificallythegrowing
peptidechain,bypreventingtheenzymepeptidyltransferase
fromaddingthesubsequentaminoacidattachedtothetRNA.
Sincethebacterialribosomalstructureishighlyconserved
acrossmost,ifnotall,bacterialspecies,itisconsideredbroad-
spectrum.Macrolidesarebacteriostaticagentsastheyonly
inhibitproteinsynthesis,although,athighdoses,theycanbe
bactericidal.
MOA of MACROLIDES
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42. GENERAL INDICATION OF MACROLIDES
•Macrolides are a group of antibiotics commonly used to treat a variety
of bacterial infections. Some general indications for Macrolides
antibiotics include:
•Respiratory Tract Infections
•Skin and Soft Tissue Infections.
•Sexually Transmitted Infections (STIs
•Ear Infections
•Strep Throat (Streptococcal Pharyngitis)
•Sinus Infections (Sinusitis
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43. GENERAL INDICATION IN DENTISTRY
•Macrolide antibiotics, such as erythromycin, azithromycin, and
clarithromycin, are occasionally prescribed in dentistry for specific
indications. Some general indications for the use of macrolides in
dentistry include:
•Management of Dental Infections
•Prophylaxis for Endocarditis
•Treatment of Periodontal Infections:
•Management of Oral Abscesses
•Adjunctive Therapy in Oral Surgery
•Management of Odontogenic Infections
•Treatment of Oral Ulcerative Conditions
•Management of Oral Mucosal Infections
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44. ADR of MACROLIDES
Macrolides are generally well-tolerated, like all medications, they
can cause adverse drug reactions (ADRs). Some of the common ADRs
associated with Macrolides include:
•GastrointestinalDisturbances:Nausea,vomiting,diarrhea,abdominal
pain,andgastrointestinaldiscomfortarefrequentlyreportedside
effectsofmacrolideantibiotics.Thesesymptomsusuallyoccurdueto
thedisruptionofthenormalgutflora.
•AllergicReactions:Allergicreactionstomacrolidescanrangefrom
mildskinrashesanditchingtosevereallergicreactions.
•Ototoxicity:Althoughuncommon,somemacrolides,especially
erythromycin,havebeenassociatedwithreversiblehearinglossor
tinnitus(ringingintheears).
•Photosensitivity,ClostridiumdifficileInfection,Hepatotoxicityarerare
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45. DOSES OF MACROLIDES
•Azithromycin :
•For most infections: The typical adult dose is 500 mg once daily for 3 days,
followed by 250 mg once daily for 7 to 10 days.
•For respiratory tract infections: The usual dose is 500 mg once daily for 3 days, or
500 mg as a single dose on day 1, followed by 250 mg once daily for 4 days.
•Clarithromycin (Biaxin):
•For most infections: The typical adult dose is 250 mg to 500 mg twice daily, taken
for 7 to 14 days.
•For pneumonia: The usual dose is 500 mg twice daily for 7 to 14 days.
•Erythromycin:
•For most infections: The usual adult dose is 250 mg to 500 mg every 6 hours, or
500 mg to 1000 mg every 12 hours, taken for 7 to 14 days.
•For whooping cough (pertussis): The typical dose is 40 mg/kg/day in divided
doses for 7 to 14 days.
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46. CONTRAINDICATIONS OF MACROLIDES
•ConcomitantUsewithErgotamineorDihydroergotamine:Macrolidescan
inhibitthemetabolismofergotalkaloids,leadingtoincreasedlevelsinthe
blood,whichmayresultinergotism(aconditioncharacterizedbysevere
peripheralvasoconstriction).Therefore,concurrentuseofmacrolideswith
ergotamineordihydroergotamineiscontraindicated.
•ConcomitantUsewithSomeStatins:Somemacrolideantibiotics,particularly
erythromycinandclarithromycin,caninhibitthemetabolismofcertainstatins
(e.g.,simvastatin,atorvastatin),leadingtoanincreasedriskofstatin-induced
myopathyorrhabdomyolysis.Therefore,cautionisadvised,andalternative
antibioticsshouldbeconsideredinpatientstakingthesestatins.
•ProlongedQTInterval:Macrolides,particularlyerythromycinand
clarithromycin,havebeenassociatedwithprolongationoftheQTintervalon
electrocardiogram(ECG).PatientswithpreexistingQTintervalprolongationor
thosetakingmedicationsknowntoprolongtheQTintervalshoulduse
macrolideswithcaution,andalternativeantibioticsmaybeconsidered.
•MyastheniaGravis:Macrolideantibiotics,especiallyerythromycinand
clarithromycin,havebeenassociatedwithexacerbationofsymptomsin
patientswithmyastheniagravisduetotheirneuromuscularblockingeffects.
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47. TETRACYCLINES
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48. TETRACYCLINES
Tetracyclineareagroupofbroad-spectrumantibiotics
thatarecommonlyusedtotreatavarietyofbacterialinfections.Theyare
namedaftertheirchemicalstructure,whichcontainsfourlinearlyfused
rings(hence"tetra-,"meaningfour,and"cycl-,"referringtocyclic
structures).Tetracyclinesworkbyinhibitingbacterialproteinsynthesis,
therebypreventingthegrowthandreproductionofbacteria.Hereare
somekeypointsaboutTetracyclines
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49. •Tetracyclinesexhibitactivityagainstawiderangeofbacteria,including
bothGram-positiveandGram-negativeorganisms,aswellasatypical
bacteriasuchasChlamydia,Mycoplasma,andRickettsiaspecies.
•CommonlyPrescribedAgents:Examplesoftetracyclinesinclude:
•Tetracycline
•Doxycycline
•Minocycline
•Demeclocycline
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50. MOA
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51. BindingtotheRibosome:Tetracyclinesbindreversiblytothe30S
ribosomalsubunitofbacteria.Specifically,theybindtothe16SrRNA
componentofthe30Ssubunitinthedecodingcenter,preventing
theattachmentofaminoacyl-tRNAtotheAsite.
PreventingProteinSynthesis:Bybindingtotheribosome,
tetracyclinesblocktheaccessofaminoacyl-tRNAtotheAsite,
therebyinhibitingtheelongationofthepolypeptidechainduring
proteinsynthesis.
DisruptionofCodon-AnticodonInteraction:Tetracyclinesinterfere
withthecodon-anticodoninteraction,whichisessentialforaccurate
translationofthemRNAsequenceintothecorrespondingamino
acidsequence.Thisdisruptionleadstotheproductionoffaulty
proteinsorprematureterminationofproteinsynthesis.
BacteriostaticActivity:Tetracyclinesexertbacteriostaticactivity,
meaningtheyinhibitbacterialgrowthandreplicationratherthan
directlykillingthebacteria.Bypreventingproteinsynthesis,
tetracyclinesimpedebacterialmultiplication,allowingthehost's
immunesystemtoeliminatetheexistingbacteria.
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52. Tetracyclinesareagroupofbroad-spectrumantibioticswitharangeofindications.Some
generalindicationsfortetracyclinesinclude:
BacterialInfections:Tetracyclinesareeffectiveagainstawidevarietyofbacterialinfections,
includingrespiratorytractinfections(suchaspneumoniaandbronchitis),urinarytract
infections,skinandsofttissueinfections,andsexuallytransmittedinfections(suchas
chlamydiaandgonorrhea).
Acne:Tetracyclinesarecommonlyusedinthetreatmentofmoderatetosevereacne
vulgarisduetotheiranti-inflammatorypropertiesandabilitytosuppressthegrowthof
Propionibacteriumacnes,abacteriumassociatedwithacne.
RickettsialInfections:Tetracyclinesarethefirst-linetreatmentforrickettsialinfections,
includingRockyMountainspottedfever,typhusfever,andQfever,aswellascertaintick-
borneinfections.
Cholera:Tetracyclinesareeffectiveinthetreatmentofcholera,abacterialinfectioncaused
byVibriocholerae,andcanalsobeusedforprophylaxisinindividualsexposedtothe
bacteria.
MalariaProphylaxis:Doxycyclineissometimesusedformalariaprophylaxisintravelersto
areaswheremalariaisendemic,particularlyinregionswherePlasmodiumfalciparumis
resistanttootherantimalarialmedications.
PeriodontalDisease:Tetracyclines,particularlydoxycycline,maybeusedasanadjunctive
therapyinthemanagementofperiodontaldiseaseduetotheiranti-inflammatoryand
antimicrobialproperties.
PepticUlcerDisease:Tetracyclines,incombinationwithotherantibioticsandprotonpump
inhibitors,maybeusedinthetreatmentofpepticulcerdiseasecausedbyHelicobacter
pyloriinfection. [email protected] 52

53. Doxycycline:Foradults:Theusualdosageformostinfectionsis100
mgorallyorintravenouslytwicedailyonthefirstday(orasasingle
initialdosefollowedby100mgevery12hours),followedbya
maintenancedoseof100mgoncedailyor50mgtwicedaily.
Forsevereinfectionsorasamalariaprophylaxis:200mgorallyor
intravenouslyoncedaily.
Minocycline:
Foradults:Theusualdosagerangesfrom100mgto200mgorally
onceortwicedaily.Thedosagemaybeadjustedbasedonthe
severityoftheinfection.
Forchildren:Thedosageisweight-based,typicallyrangingfrom4to
8mg/kgperday,dividedintotwodoses.
Tetracycline:Foradults:Thetypicaldosageis500mgorallyfourtimes
daily.
Forchildren:Thedosageisweight-based,typicallyrangingfrom25to
50mg/kgperdaydividedintofourdoses.
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54. AdverseDrugReactions(ADRs):
a.GastrointestinalDisturbances:Tetracyclinesarenotoriousforcausing
gastrointestinalsideeffects,includingnausea,vomiting,diarrhea,andabdominalpain.
b.Photosensitivity:Tetracyclinescanmaketheskinmoresensitivetosunlight
(photosensitivity),leadingtoincreasedriskofsunburn,rash,orotherskinreactionsupon
exposuretosunlightorultraviolet(UV)radiation.
c.DentalDiscolorationandBoneGrowthInhibition:Tetracyclinescan
causepermanentdiscolorationofdevelopingteethandinhibitbonegrowthinfetuses,
infants,andchildrenyoungerthan8yearsold.Therefore,tetracyclinesaregenerally
avoidedduringpregnancyandinchildrenunder8yearsofageunlesstherearenosuitable
alternatives.Hepatotoxicity,RenalToxicity,AllergicReactions,
Contraindications:
a.PregnancyandLactation:Tetracyclinesarecontraindicatedduringpregnancy,
particularlyduringthesecondandthirdtrimesters,duetotheriskofdentaldiscoloration
andinhibitionofbonegrowthinthefetus.Theyarealsocontraindicatedinbreastfeeding
mothersastetracyclinescanpassintobreastmilkandharmtheinfant'sdevelopingteeth
andbones.
b.ChildrenUnder8YearsOld:Tetracyclinesaregenerallycontraindicatedinchildren
youngerthan8yearsoldduetotheriskofdentaldiscolorationandinhibitionofbone
growth.SevereHepaticorRenalImpairment,d.KnownAllergyorHypersensitivity,
MyastheniaGravis:
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55. GENERAL INDICATIONS IN DENTISTRY
•Periodontal Infections: Tetracyclines are effective against the bacteria commonly
associated with periodontal disease, such as Porphyromonasgingivalisand
Aggregatibacteractinomycetemcomitans. They can be used as adjunctive therapy to
mechanical debridement in the treatment of periodontitis.
•Dental Abscesses: Tetracyclines can be prescribed to treat dental abscesses caused
by bacterial infections. They help to reduce inflammation and control the spread of
infection.
•Adjunctive Therapy for Oral Surgery: Tetracyclines may be used as adjunctive
therapy in oral surgery procedures to prevent postoperative infections and promote
healing.
•Lichen Planus: Tetracyclines may be prescribed to manage oral lichen planus, an
inflammatory condition that affects the mucous membranes inside the mouth.
•Peri-Implantitis: Tetracyclines may be used as part of the treatment for peri-
implantitis, an inflammatory condition affecting dental implants, to control bacterial
infection and inflammation.
•Oral Ulcerations: Tetracyclines may be used to manage oral ulcerations, including
aphthousulcers, by reducing inflammation and promoting healing.
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56. FLUOROQUINOLONES
Fluoroquinolonesareaclassofsyntheticantibioticsthattarget
bacterialDNAgyraseandtopoisomeraseIVenzymes,interferingwith
DNAreplication,repair,andtranscription.Byinhibitingthese
essentialbacterialenzymes,fluoroquinolonespreventbacterial
growthandproliferation,ultimatelyleadingtobacterialcelldeath.
Theyaregenerallybactericidal,meaningtheydirectlykillbacteria
ratherthanjustinhibitingtheirgrowth.
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57. Fluoroquinolonesare classified into four generations based on their spectrum of activity and
pharmacokinetic properties:
First-generationfluoroquinolones:NALIDIXICACID,which
havealimitedspectrumofactivityprimarilyagainstGram-
negativebacteria,especiallyEscherichiacoli
Second-generationfluoroquinolones:CIPROFLOXACINAND
OFLOXACIN.Theyhaveabroaderspectrumofactivity
comparedtofirst-generationagents,includingactivityagainst
Gram-negativebacteriasuchasPseudomonasaeruginosaand
someGram-positivebacterialikeStaphylococcusaureus.
Third-generationfluoroquinolones:LEVOFLOXACINAND
MOXIFLOXACIN.Theyhaveanexpandedspectrumofactivity
comparedtoearliergenerations,withincreasedpotency
againstGram-positivebacteriasuchasStreptococcus
pneumoniaeandatypicalpathogenslikeMycoplasma
pneumoniaeandLegionellapneumophila.
Fourth-generationfluoroquinolones:GEMIFLOXACINAND
GATIFLOXACIN.Theyhaveaspectrumofactivitysimilarto
third-generationagentsbutmayhaveimprovedefficacy
againstcertainGram-positivebacteriaandanaerobes.
•Fifth-generation fluoroquinolones: Example: Delafloxacin
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58. MODE OF ACTION
•Fluoroquinolonesexerttheirantimicrobialactivityprimarilyby
inhibitingtwobacterialenzymes:DNAgyrase(topoisomeraseII)and
topoisomeraseIV.TheseenzymesplaycrucialrolesinbacterialDNA
replication,transcription,repair,andrecombination.Byinterfering
withtheseprocesses,FLUOROQUINOLONESdisruptbacterialDNA
metabolism,leadingtoinhibitionofbacterialgrowthandultimately
celldeath.
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59. •InhibitionofDNAGyrase:DNAgyraseisresponsibleforintroducing
negativesupercoilsintobacterialDNAduringreplicationand
transcription.FluoroquinolonesbindtotheAsubunitofDNAgyrase,
formingacomplexwithmagnesiumionsandDNA.Thiscomplex
preventstheresealingofDNAstrandsaftertheyhavebeencleavedby
theenzyme,leadingtotheaccumulationofDNAbreaksandinhibitionof
DNAreplication.
•InhibitionofTopoisomeraseIV:TopoisomeraseIVisinvolvedinthe
separationofinterlinkeddaughterchromosomesduringbacterialcell
division.FLUOROQUINOLONESalsoinhibitthisenzymebybindingtoits
subunitsandinterferingwithitsfunction.InhibitionoftopoisomeraseIV
resultsintheaccumulationofDNAdouble-strandbreaksandimpedes
bacterialcelldivision.
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60. [email protected] 60

61. INDICATIONS
Fluoroquinolones are a class of antibiotics commonly used to treat
various bacterial infections due to their broad-spectrum activity
against both Gram-positive and Gram-negative bacteria. Here are
some general indications for the use of Fluoroquinolones:
Respiratory Tract Infections
Urinary Tract Infections (UTIs)
Gastrointestinal Infections
Skin and Soft Tissue Infections
Sexually Transmitted Infections (STIs)
Intra-abdominal Infections
Bone and Joint Infections
Other Infections:
Prostatitis
Infectious exacerbations of chronic obstructive pulmonary disease
(COPD)
Post-exposure prophylaxis for anthrax
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62. Adverse Drug Reactions (ADRs):
a. Gastrointestinal Disturbances: Nausea, vomiting, diarrhea, and abdominal
discomfort are common gastrointestinal side effects of fluoroquinolones.
b. Central Nervous System Effects: Some patients may experience headaches,
dizziness, or lightheadedness. Rarely, fluoroquinolones can cause more serious
adverse neurological effects such as seizures, confusion, hallucinations, and
peripheral neuropathy.
c. Tendinopathy and Tendon Rupture: Fluoroquinolones have been associated
with an increased risk of tendinopathy and tendon rupture, particularly involving
the Achilles tendon. This risk is higher in elderly patients, those concurrently
taking corticosteroids, and individuals with a history of tendon disorders.
d. Photosensitivity: Fluoroquinolones can increase sensitivity to sunlight, leading
to sunburns, rash, or other skin reactions upon exposure to UV radiation.
Apart from some rare ADR are Cardiovascular Effects, Hypersensitivity
Reactions, Hepatotoxicity, Musculoskeletal Effects in Pediatric Patients
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63. Contraindications
•a.PregnancyandLactation:Fluoroquinolonesarecontraindicated
duringpregnancyandbreastfeedingduetopotentialadverseeffectson
fetalcartilagedevelopmentandpossibleharmtotheinfant.
•b.PediatricUse:Fluoroquinolonesaregenerallycontraindicatedin
childrenandadolescentsduetoconcernsaboutadverseeffectson
musculoskeletaldevelopment,includingarthropathy.
•c.KnownHypersensitivityorAllergy:Patientswithahistoryof
hypersensitivityorallergicreactionstofluoroquinolonesoranyoftheir
componentsshouldnotreceivethesemedications.
•d.TendonDisordersorTendonRuptureHistory:Patientswithahistory
oftendondisordersortendonrupturerelatedtofluoroquinoloneuse
shouldavoidthesemedications.
•e.SeizureDisorders:Fluoroquinolonesshouldbeusedwithcautionor
avoidedinpatientswithahistoryofseizuresorpredisposingfactorsfor
seizuresduetotheriskofloweringtheseizurethreshold.
•f.MyastheniaGravis:Fluoroquinolonescanexacerbatesymptomsof
myastheniagravis,aneuromusculardisordercharacterizedbymuscle
weaknessandfatigue.
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64. Fluoroquinolones in clinical dentistry
•ManagementofOdontogenicInfections:Fluoroquinolonesmaybe
prescribedforthetreatmentofodontogenicinfections,including
dentalabscesses,periapicalabscesses,andperiodontalinfections.
Theyareeffectiveagainstawiderangeofbacteriacommonly
associatedwithdentalinfections,includingbothaerobicand
anaerobicpathogens.
•ProphylaxisforDentalProcedures:Incertaincases,especiallyfor
patientswithunderlyingmedicalconditionsorprostheticheart
valves,prophylacticantibioticsmayberecommendedbefore
dentalprocedurestopreventinfectiveendocarditis.
Fluoroquinolonesmaybeconsideredasanalternativeforpatients
whoareallergictopenicillinoramoxicillin.
•TreatmentofAcuteNecrotizingUlcerativeGingivitis(ANUG):
FluoroquinolonesmaybeprescribedforthetreatmentofANUG,
alsoknownas"trenchmouth."ANUGisasevereformofgingivitis
characterizedbypainful,bleedinggumsandfoulbreath.
Fluoroquinolonescanhelpmanagetheinfectionandreduce
symptoms.
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65. •AdjunctiveTherapyforPeriodontalDisease:Insomecasesofsevereor
refractoryperiodontaldisease,adjunctivesystemicantibioticsmaybe
prescribedalongwithscalingandrootplaning(SRP)toenhance
treatmentoutcomes.Fluoroquinolonesmaybeoneoftheantibiotics
consideredinsuchcases,althoughtheyarenottypicallyfirst-lineagents
forperiodontaltherapy.
•ManagementofOrofacialInfections:Fluoroquinolonesmayalsobe
usedinthemanagementoforofacialinfections,includingcellulitis,
Ludwig'sangina,andothersofttissueinfectionsoftheheadandneck
region.Theycanprovidebroad-spectrumcoverageagainstbacterial
pathogenscommonlyassociatedwiththeseinfections.
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66. AMINOGLYCOSIDES
AMINOGLYCOSIDESareaclassofantibioticsthatareprimarilyused
totreatsevereinfectionscausedbyGram-negativebacteria.They
workbyirreversiblybindingtothebacterialribosome,specificallythe
30Ssubunit,whichdisruptsproteinsynthesisandultimatelyleadsto
bacterialcelldeath.AMINOGLYCOSIDESareusuallybactericidal,
meaningtheydirectlykillbacteriaratherthanjustinhibitingtheir
growth.
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67. Aminoglycosidescan be classified based on their
chemical structure and include:
•Traditional Aminoglycosides:
•Streptomycin
•Gentamicin
•Tobramycin
•Amikacin
•Semisynthetic Aminoglycosides:
•Netilmicin: Netilmicin is a semisynthetic derivative of gentamicin with a similar
spectrum of activity.
•Neomycin: Neomycin is primarily used topically due to its significant
nephrotoxicity and ototoxicity when administered systemically. It is often found
in combination products for skin infections or as a component of bowel
preparation regimens.
•Paromomycin: Paromomycin is used primarily for the treatment of intestinal
parasites such as Entamoeba histolytica and Giardia lamblia.
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68. Mode of Action
Aminoglycosides are a group of antibiotics that inhibit bacterial protein
synthesis by targeting the bacterial ribosome. The mechanism of
action of aminoglycosides involves several steps:
1.Bindingtothe30SRibosomalSubunit:Aminoglycosidesinitiallybind
tothe30Ssubunitofthebacterialribosome.Thisbindingoccurs
throughelectrostaticinteractionsbetweenthepositivelycharged
aminogroupsoftheAMINOGLYCOSIDEmoleculeandthenegatively
chargedphosphatebackboneoftheribosomalRNA.
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69. 2.DistortionoftheRibosome:Onceboundtotheribosome,
AMINOGLYCOSIDESinduceconformationalchangesintheribosomal
structure.Thisdistortiondisruptstheproperalignmentoftheribosomal
subunitsandpreventstheaccuratepositioningoftransferRNA(tRNA)
moleculesduringproteinsynthesis.
3.InhibitionofInitiationComplexFormation:AMINOGLYCOSIDES
interferewiththeformationoftheinitiationcomplex,whichisessential
fortheinitiationofproteinsynthesis.Bydisruptingtheproperassembly
oftheribosome-mRNA-tRNAcomplex,AMINOGLYCOSIDESpreventthe
initiationoftranslation.
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70. 4.MisreadingofmRNA:AMINOGLYCOSIDEScanalsocauseerrorsin
mRNAdecodingduringtheelongationphaseofproteinsynthesis.They
inducethemisreadingofmRNAcodonsbytheribosome,leadingtothe
incorporationofincorrectaminoacidsintothegrowingpolypeptide
chain.
5.InhibitionofTranslocation:AMINOGLYCOSIDESinhibitthemovement
oftheribosomealongthemRNAmoleculeduringtheelongationphase.
ThisinhibitionpreventsthepropertranslocationoftRNAmoleculesand
theadvancementoftheribosomealongthemRNAstrand,effectively
haltingproteinsynthesis.
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71. Mode of Action
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72. INDICATION OF AMINOGLYCOSIDES
TheiruseisgenerallyreservedforinfectionscausedbyaerobicGram-
negativebacteriaandcertainGram-positivebacteria.
•SeriousGram-NegativeInfections:Aminoglycosidesareoftenusedas
first-linetherapyforsevereinfectionscausedbyGram-negativebacteria,
includingPseudomonasaeruginosa,Escherichiacoli,Klebsiella
pneumoniae,andAcinetobacterbaumannii.Theseinfectionsmay
includesepsis,pneumonia,urinarytractinfections,andintra-abdominal
infections.
•SevereHospital-AcquiredInfections:Aminoglycosidesmaybeusedas
partofempirictherapyforseverehospital-acquiredinfections,
especiallywhenthecausativepathogensarelikelytobemultidrug-
resistantGram-negativebacteria.
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73. Some other indications like..
•Combination Therapy for Enterococcal Endocarditis,
•Mycobacterial Infections,
•Cystic Fibrosis
•Neonatal Sepsis
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74. Dosage of Aminoglycosides
•Gentamicin:
•For adults, the usual intravenous (IV) dose is 3 to 5 mg/kg/day, divided into 3
equal doses every 8 hours. In some cases, higher doses may be used for severe
infections.
•For pediatric patients, the dose is typically 2 to 3 mg/kg/dose every 8 hours.
•Renal function should be monitored closely, and dosing adjustments may be
necessary in patients with impaired renal function.
•Tobramycin:
•The typical adult IV dose is 3 to 5 mg/kg/day, divided into 2 to 3 equal doses
every 8 hours.
•Pediatric dosing is usually 2 to 3 mg/kg/dose every 8 hours.
•Similar to gentamicin, dosing adjustments are needed in patients with renal
impairment.
•Amikacin:
•Amikacindosing can vary widely based on the indication, severity of infection,
and patient factors. A common adult dose for serious infections is 15 to 20
mg/kg/day, divided into 2 to 3 doses every 8 to 12 hours.
•Pediatric dosing ranges from 15 to 22.5 mg/kg/day, divided into 2 to 3 doses.
•Renal function must be closely monitored, and dosing adjustments are essential,
especially in patients with impaired renal function.
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75. ADVERSE DRUG REACTION AND
CONTRAINDICATIONS OF AMINOGLYCOSIDES
•Nephrotoxicity:Aminoglycosidescancausedamagetothekidneys,leadingto
acutetubularnecrosis.Thisriskisincreasedwithhigherdoses,prolonged
therapy,andpre-existingrenalimpairment.Monitoringofrenalfunction,
includingserumcreatinineandurineoutput,isessentialduringtreatment.
•Ototoxicity:Aminoglycosidescancausedamagetotheinnerear,resultingin
irreversiblehearinglossandvestibulardysfunction.Thisriskisgreaterwith
prolongedtherapy,higherdoses,andinpatientswithpre-existinghearing
impairmentorreceivingotherototoxicmedications.Patientsshouldbe
monitoredforsymptomsofhearingloss,tinnitus,andvertigo.
•NeuromuscularBlockade:Aminoglycosidescaninterferewithneuromuscular
transmission,leadingtomuscleweaknessandrespiratoryparalysis,particularly
inpatientswithmyastheniagravisorthosereceivingneuromuscularblocking
agents.Closemonitoringisrequiredinsuchpatients,andcautionshouldbe
exercisedwhenadministeringaminoglycosidesconcurrentlywithotherdrugs
thataffectneuromuscularfunction.
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76. •ContraindicationsinPregnancyandLactation:Aminoglycosidesare
generallycontraindicatedinpregnantwomen,especiallyduringthe
secondandthirdtrimesters,duetotheriskofototoxicityand
nephrotoxicitytothefetus.Theseantibioticscanalsopassintobreast
milk,posingarisktonursinginfants.
•RenalImpairment:Aminoglycosidesshouldbeusedwithcautionin
patientswithpre-existingrenalimpairment,astheyareprimarily
eliminatedbythekidneys.Dosageadjustmentsarenecessarybasedon
renalfunction,andmonitoringforsignsofnephrotoxicityisessential.
•NeuromuscularDisorders:Patientswithneuromusculardisorders,such
asmyastheniagravisorParkinson'sdisease,maybeatincreasedriskof
neuromuscularblockadewhentreatedwithaminoglycosides.Close
monitoringanddoseadjustmentsmayberequired.
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77. IMPLICATION OF AMINOGLYCOSIDES IN
CLINICAL DENTISTRY
Aminoglycosideantibioticsareoccasionallyusedinclinical
dentistry,primarilyforthetreatmentoforalinfectionscausedby
susceptiblebacteria.However,theiruseislimitedduetopotential
adverseeffectsandtheavailabilityofalternativeantibioticsthatare
oftenpreferred.
1.TreatmentofSevereOralInfections:Incasesofsevereoral
infections,suchasdeepabscessesorosteomyelitis,wherethecausative
bacteriaareknownorsuspectedtobesusceptibletoaminoglycosides,
theseantibioticsmaybeconsideredaspartofamultidrugregimen.
However,theyaretypicallyreservedforcaseswhereotherantibiotics
areineffectiveorcontraindicated.
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78. •AdjunctiveTherapyinPeriodontalTreatment:Aminoglycosideshave
beeninvestigatedasadjunctivetherapyinthetreatmentofperiodontal
diseases,particularlyincasesofaggressiveorrefractoryperiodontitis.
Theymaybeusedincombinationwithmechanicaldebridementand
otherantibioticstotargetspecificperiodontalpathogens.
•ManagementofOdontogenicInfections:Aminoglycosidesmaybeused
inthemanagementofodontogenicinfections,suchasthoseinvolving
themaxillofacialregion,whenbroaderspectrumantibioticsarerequired
orwhenthereisaknownsusceptibilityofthecausativebacteria.
•TreatmentofComplications:Aminoglycosidesmaybeusedinthe
treatmentofcomplicationsarisingfromdentalprocedures,suchas
postoperativeinfectionsorosteomyelitis.However,theiruseshouldbe
basedoncultureandsusceptibilitytesting,andconsiderationshouldbe
giventopotentialadverseeffects.
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79. SULFONAMIDES
•Sulfonamides,alsoknownassulfadrugsor
sulphonamides,areagroupofsynthetic
antimicrobialagentsthatinhibitthegrowthand
reproductionofbacteriabyinterferingwiththe
synthesisoffolicacid,acrucialnutrientforbacterial
survival.Sulfonamidesareclassifiedbasedontheir
chemicalstructureandmechanismofaction.
•classificationtheSulfonamidesantimicrobials
accordingtotheirtherapeuticutility….
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80. I-Sulfonamides employed for the treatment of systemic infection.
A.Short acting : Sulfadiazine, sulfadimidine, Sulfacetamide,
Sulfafurazone, sulfamethizole.
B.Intermediate : Sulfamethoxizole
C.Long Acting: Sulfadoxine, sulfamethoxy-pyridazine.
II-Oral Sulfonamide for ulcerative colitis: Sifasalazine
III. Sulfonamides for topical use: Silver Sulfadiazine, Sulfacetamide,
Mefinide
IV.Sulfones: Dapsone(diaminodiphenylsulfone): Used in the treatment
of leprosy
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81. •Folicacid,orfolate,playsavitalroleinbacterialmetabolismand
growthbyservingasacofactorinseveralessentialbiochemical
pathways.Bacteriaareunabletouptakepreformedfolicacidfrom
theenvironmentandmustsynthesizeitdenovothroughaseriesof
enzymaticreactions.
•Folicacidisacrucialcofactorinbacterialmetabolism,playing
essentialrolesinnucleicacidsynthesis,aminoacidmetabolism,and
othervitalcellularprocesses.Targetingthesynthesisoffolicacidisa
commonstrategyforantimicrobialtherapy,asinhibitionofthis
pathwayselectivelytargetsbacterialgrowthwhilesparinghostcells.
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82. MOA
Sulfonamides,exerttheirantimicrobialeffectsbyinterferingwiththe
synthesisoffolicacid,acrucialcomponentforthesynthesisofnucleicacids
(DNAandRNA)inbacteria.Themechanismofactionofsulfonamides
involvesthefollowingsteps:
•CompetitiveInhibitionofDihydropteroateSynthase(DHPS):Sulfonamides
structurallyresemblethesubstratepara-aminobenzoicacid(PABA),which
isaprecursorrequiredforthesynthesisofdihydropteroicacid,aprecursor
inthefolicacidbiosynthesispathway.Sulfonamidescompetitivelyinhibit
theenzymedihydropteroatesynthase(DHPS),whichcatalyzesthe
condensationofPABAwithdihydropteroatetoformdihydropteroicacid.By
blockingthisstep,sulfonamidespreventtheproductionofdihydropteroic
acid,thusinhibitingthesynthesisoftetrahydrofolicacid,theactiveformof
folicacidinbacteria.
•InhibitionofTetrahydrofolicAcidSynthesis:Sincebacteriaareunableto
utilizeexogenoussourcesoffolicacidandmustsynthesizetheirown,the
inhibitionoftetrahydrofolicacidsynthesisbysulfonamidesdisruptsvarious
metabolicpathwaysthatdependonfolatederivatives.Thesepathways
includethesynthesisofnucleicacids(DNAandRNA),aminoacids,and
otheressentialcellularcomponentsrequiredforbacterialgrowthand
replication.
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83. [email protected] 83