Download - Drug Drug Class Mechanism of Action Indications Adverse ...€¦ · 2/12/2017 · Cell Wall Synthesis Inhibitors Bacteriocidal 4-Member Nitrogen Containing B-Lactam Ring Inhibit

Drug DrugClass MechanismofAction Indications AdverseEffects Resistance

B-LactamAntibiotics

CellWallSynthesisInhibitorsBacteriocidal

4-MemberNitrogenContainingB-LactamRingInhibitCellWallSynthesis

---------------------------------------Bacteriocidal:

MoreEffectivewhentheCellsareActivelyDividing/GrowingandSynthesizingCellWall

PenicillinB-Lactam


5-MemberSulfurContainingThiazolidineRingFusedtoaB-LactamRing

------------------------------------------------------------------BacterialCellWall:

Cross-LinkedPolymerofPolysaccharidesandPentapeptides

PenicillinsInterferewithCellWallSynthesis(Peptidoglycan)byBindingPenicillinBindingProtein(PBP)

ThisInhibitsCross-LinkingofPeptideChains(TranspeptidationInhibition)

-----------------------------------------------------------------------ResultsinFormationofCellWallDeficienctBacteria,

WhichareEasilyLysed(CellDrawsWateruntilitBursts)

MoreEffectivewhenCellsareActivelyDividing/Growing(Bacteriocidal)

ActivityDependsontheConcentrationaboutMICfortheEntireDosing

Interval

HypersensitivityReactions:Anaphylaxis(Cross-AllergicReactions)

UrticarialRashes(Common)Angioedema:SwellingofLips,Tongue,PeriorbitalAreas

Anaphylaxis:DoNotUseANYB-LactamAfterReactionHappensDesensitizationCanBeAccomplishedwithGradually

IncreasingDosesofPenicillin(EspeciallyinEnterococcalEndocarditisorNeurosyphilis)

MajorAntigenicDeterminant:DegradationProductsofPenicillins:

PenicilloicAcidProductsofAlkalineHydrolysisBoundtoHostProtein

------------------------------------------------------------Nephrotoxicity:Methicillin

Neurotoxicity:HighDoses=SeizuresandConvulsionsPlateletDysfunction:Carbenicillin,Ticarcillin

Neutropenia:NafcillinGIDistress:Nausea,Vomiting,Diarrhea(Ampicillin!)

PseudomembranousColitis+VaginalCandida:AmpicillinJarish-HerxheimerReaction:PenicillinInjectedinaSyphiliticPatientProducesFever,Malaise,JointPain,

ExasterbationofLesions,Hypotension--DoNOTInterrupttheTherapy.

CellWallisUniquetoBacteriasoPenicillinsareRelativelyNon-Toxicto

Humans--------------------------------------------------

Resistance:NaturalResistance:

OccursinOrganismsthatLackaPeptidoglycanCellWall(Mycoplasma )orHaveCellsWallsImpermeabletoDrugs

AcquiredResistance:OccursbyPlasmidTransfer(SignificantClinicalProblem)

----------------------------------------------------MechanismsofResistance:

EnzymaticHydrolysisofB-LactamRingbyB-LactamaseEnzyme(MostCommon)

------------------StructuralChangeofPBPs(MRSA)

-----------------ChangeinPorinStructure(Pseudomonas)

---------------Gram-OrganismsMayHaveEffluxPumps,

whichEfficientlyTransportSomeB-LactamAntibioticsfromthePeriplasm

AcrosstheOuterMembrane

PenicillinGPenicillinV

StandardNatrualPenicillinsB-Lactam


NarrowSpectrumSusceptibletoHydrolysisbyB-Lactamases

------------------------------HighlyWaterSolubleStableinDryState

SolutionsareFreshlyPreparedFormulatedtoDelayAbsorption

ResultlsinProlongedBloodandTissueConcentration-------------------------------------------------------

PenicillinG:(BenzylPenicillin)Acid-Labile

Half-Life:30MinutesParenteralRepository(Depot)FormforIMInjection

DestroyedbyGastricAcid(GiveIV!)DistributedWidely(DoesNOTCrossBBB)

DuringInflammation,(Meningitis)EntryisFacilitatedExcreted,UnchangedinUrine

--------------ProbenecidInhibitsTubularSecretionofPenicillin

ThisRaisesBloodPenicillinLevels----------------------------------------------------------------

PenicillinV:AcidResistance

Oral

Spectrum:GreatestActivityAgainst:Gram+andGram-Cocci

Non-B-LactamaseProducingAnaerobeNOTACTIVEAganistGram-RodsGoodActivity:TreponemaPallidum

----------------------------------------HighIncidenceofResistantStrains

------------------------------------PenicillinG:

DoC:Syphilis

ProphylacticDrug:RheumaticHeartDisease

(RheumaticFever)GonorrheaSyphilis

------------------------------------PenicillinV:

IndicatedinMinorInfectionsBecauseItIs:

PoorlyBioavailableDosing4x/Day

NarrowSpectrum(AmoxicillinUsedInstead)

HighTheraputicIndexPruriticRashAnaphylaxis

SafetoUseinPregnancy

MethicillinNaficillinOxacillinClocacillinDicloxacillin

Anti-StaphylococcalPenicillins(PenicillinaseResistant)

B-LactamCellWallSynthesisInhibitors

Bacteriocidal

VeryNarrowSpectrumResistanttoStaphylococcalB-Lactamases-------------------------------------------------------

Nafcillin:LipidSolubleCrossesBBB

ExcretedinBileCANBEGIVENinRenalImpairment

Spectrum:Staphylococci(NotMRSA)

StreptococciNOTACTIVEAgainst:

Enterococci,AnaerobicBacteria,Gram-Cocci/Rods

----------------------------------------StaphylococcalInfections:Anti-StaphPenicillins

DrugofChoice:NafcillinOxacilin

-----------------------------IftheStaphis"MethicillinResistant",

treatwithVancomycin---------------

IftheStaphis"VancomycinResistant",treatwithLinezolid,Quinupristin,

Dalfopristin

Methicillin:NephrotoxicityNoLongerUsed

-------------------------------------------IsoxazolylPenicillins:

Cloxacillin,Oxacillin,DicloxacillinFoodInterfereswithAbsorption

Administer1HourBefore/AfterMeals----------------------------------------------

Nafcillin:Neuropenia

MechanismsofResistance:AlteredPBPs

AmpicillinAmoxicillin

AminopenicillinsB-Lactam


ExtendedSpectrumB-LactamaseSensitive

-------------------------------------------------------CanbeCombinedwithB-LactamaseInhibitors:

ClavulanicAcid,Sulbactam,Tazobactam--------------------------------------------

Ampicillin:Amoxicillin:

BetterOralBioavailability

Spectrum:GramPositiveCocci

(NOTSTAPH)GreaterActivityAgonist

Gram-BacteriathanPenicillin---------------------------------------------------

Ampicillin:DoC:ListeriaMonocytogenes

(Meningitis)------------------

SalmonellaGastroenteritisTyphoidCarrierState

Shigellosis----------------------------------------------

Amoxicillin:URTIs

(Pharyngitis,Sinusitis,OtitisMedia,Bronchitis)

-------------------UTIs:

Enterobacteriaceae,E.Coli-------------------

BorreliaBurgdorgeri(LymeDisease)H.Pylori

Ampicillin:FoodInterfereswithAbsorption

Causes:Diarrhea

PeudomembranousColitis---------------------------------

Amoxicillin:CompletelyAbsorbed

FoodDoesNOTInterferewithAbsorptionNoDiarrhea

NoPseudomembranousColitis

MechanismsofResistance:InactivationbyB-Lactamase(Penicillinase)

HighestResistance:E.ColiandH.Influenzae

-------------ProtectAgainstResistance:

GiveClavulanicAcidorSulbactam

CarbenicillinTicarcillinPiperacillinAzlocillinMezlocillin

Anti-PseudomonalPenicillinsB-Lactam


ExtendedSpectrumB-LactamaseSensitive

-------------------------------------------------------

Carboxypenicillins:Carbenicillin,Ticarcillin:

NosocomialPseudomonasInfections:BurnPatients

CysticFibrosisPatients----------------

Ureidopenicillins:Piperacillin,Azlocillin,Mezlocillin

PseudomonasEnterobacterKlebsiella

HighDoseCarbenicillin,Ticarcillin:InterfereswithPlateletFunction:Bleeding

ClavulanicAcidSulbactamTazobactam(Augmentin)

B-LactamaseInhibitors

Lactamases:EnzymesProducedbyGram+/-OrganismsthatInactivate

B-LactamAntibioticsbyOpeningB-LactamRing---------------------------------------------------------------------------B-LactamaseInhibitorsResembleB-LactamMolecules,but,byThemselves,DoNOTHaveSignificantAnti-

BacterialActivity.

AvailableOnlyinFixedCombinationswithSpecificPenicillins:

Preparations:Amoxicillin+ClavulanicAcid(Oral)

Ticarcillin+ClavulanicAcid(Parenteral)Ampicillin+Sulbactam(Parenteral)

Piperacillin+Tazobactam(Parenteral)


CephalosporinsBacteriocidal

MoreStabletoManyBacterialB-LactamasesBroaderSpectrumofActivity

Allhave7-AminocephalosporanicAcidMechanismofAction:SameasPenicillin

1-4GenerationsGram-BacterialActivity:Increasesfrom1-->4

NotActiveAgainstLAME:ListeriaMonocytogenes

Atypital(Chalmydia,Mycoplasma)MRSA

Entercocci----------------------------

PoorOralAbsorption(GiveIV/IM)GoodBodyDistribution

Cefoperazone,Cefamondole,Cefotetan,Cefmetazole:Bleeding(Hypoprothrombinemia)

MTT,MethylthiotetrazoleSideChainGiveVitaminK--------------------------------------------------------

Diarrhea--------------------------------------------------------

Cephaloridine:Nephrotoxicity(Withdrawn)

GrowingResistanebyStrainsofE.ColiandKlebsiella

MechanismofResistance:SameasPenicillin

-------------------------------------------HypersensitivityReactions:

AnaphylaxisFever

SkinRashesCompleteCross-AllerginicityBetweenIndividualCephalosporinsandPartialCross-AllerginicitywithPenicillins-----------------------------------------------

IfpatienthashistoryofAnaphylaciswithPenicillins,doNOTgiveCephalosporinsGram+Organisms:GiveMacrolidesGram-Organisms:GiveAztreonam

Cefazolin---------------CephalexinCefadroxil

First-GenerationCephalosporins

DoesNotCrossBBB(CannotUseinMeningitis)WaterSoluble

(EliminatedbyKidneyGFandTubularSecretion)ProbenecidIncreasesSerumLevelSubstanstially

HighActivityAgainstGram+Cocci(NOTMRSA)

WeakGram-Activity(Pseudomonas)Effective:(PEcK)ProteusMirabilis

E.ColiKlebsiella

--------------------------------------Cefazolin:(Parenteral)

SurgicalProphylaxisAgainstGram+Bacteria

OrthopedicSurgery(PenetratesBone)------------------

Cephalexin:(Oral):URTIs(Pharyngitis)

Penicillin/Sulfonamide-ResistantUTIs------------------

Cefadroxil:(Oral)

CefuroximeCefamondoleCefoxitinCefotetan

Cefmetazole---------------Cefaclor

CefuroximeAxetil

Second-GenerationCephalosporins

Cefuroxime,Cefamondole,Cefaclor:ActiveAgainstH.InfluenzaeNOTActiveAgainstB.Fragilis

-------------------------------------------------------------------Cefoxitin,Cefotetan,Cefmetazole:

ActiveAgainstB.FragilisNOTActiveAgainstH.Influenzae

HighGram-Activity(B.Fragilis)Effective:(HENPEcK)HemophilusInfluenzaeEnterobacteraAerogenes

N.Meningitis+PEcK

-------------Upper/LowerRITsAnaerobicInfections

Community-AcquiredPneumonias-----------------------------------------

CefuroximeCefamondoleCefoxitinCefotetan

Cefmetazole:(Parenteral)----------------Cefaclor

CefuroximeAcetil:(Oral)

CefuroximeCANCrossBBB,butislesseffectivethanCeftriaxoneorCefotaxime,andisnotused.

CefotaximeCeftriaxoneCeftazidimeCefoperazone

---------CefiximeCefdinirCefibuten

CefpodoximeProxetil

Third-GenerationCephalosporins

ExpandedGramNegativeCoverageResistancetoMostLactamases

-----------------------------------------------------------CANENTERBBB

Excretion:BiliaryTract(SafeinRenalInsufficiency)

HighlyActiveAgainstGram+ANDGram-Cocci

ENHANCEDActivityAgainstGram-Bacilli

(HENPEcK)Pseudomonas,Serratia,Citrobacter,

Providencia--------------------------

EmpiricManagementofSepsisofUnknownCauseCeftazidime:

UsedinNeutropenicPatientsPseudomonas(Cefoperazone)----------------------------------------Ceftriaxone/Cefotaxime:

DoFforMeningitis:Pneumococci,Meningococci,H.Influenzae,Gram-Rods

NOTLISTERIAMONOCYTOGENES---------------------

Cefixime:UTIs

------------------------------------------TyphoidFever

1stGenerationsAreBetteratGram+Cocci,butthesehaveawiderspectrum.

CefepimeCefpirome

Fourth-GenerationCephalosporins

MoreResistancetoMost-BetaLactamases

CombinesGram+Activityof1stGenwithWiderGram-Activityof3rdGen

(DOESNOTINCLUDEMRSA)------------Cefepime:

PseudomonasEnterobacteriacaeae

S.AureusS.PneumoHemophilusNeiserria------------

CeftarolineFosamil:Pro-DrugofCeftarolineCommunityAcquiredBacterialPneumonia

AcuteBacterialSkinInfections


DoripenemErtapenemImipenemMeropenem

Carbapenems

MechanismofAction:SameasPenicillinandCephalosporin

B-LactamaseResistantException:

CarbapenemasesMetallo-B-Lactamases-----------------------------

IV/IMInjectionsErtapenem:

GiveWith1%Lidocaine(PreventsIrritation)

Spectrum:MostPotent

WidestSpectrumLactamsActiveAgainstPenicillinase-Producing

Gram+Cocci,Gram-Rods(Pseudomonas)AnaerobesErtapenem:

CannotBeUsedforPseudomonas------------------------------------------

UsedinHospitalforEmpiricUseofSevere,Life-ThreateningInfections

---------------------------DrugofChoice:Enterobacter

DrugFever:PartialCross-AllergenicitywithPenicillin

Imipenum Carbapenems

LimitingFeature:HydrolysisbyDehydropeptidasebyBrushBorderTubular

CellsofKidneyPrevention:

GiveCilastatin:InhibitsRenalDehydropeptidase

IfCilastatinIsn'tGiven,MetabolitesFormedbyDehydropeptidasearePotentiallyNephrotoxic

---------------------------------------------CausesSeizures


Aztreonam Monobactams

MechanismofAction:SameasPenicilin,Cephalosporins,Carbapenems

B-LactamaseResistant---------------------------------------------------

IV/IMInjections(OnlyIVforGram-Rods)

UsedforAerobicGram-RodsNOACTIVITYAgainst:Gram+orAnaerobes

-------------------------------------------------SafeinPatientswithPENICILLIN

ALLERGIES-------------------------------

UsedinHospitalAcquiredInfectionsandinPseudomonalInfectionswith

PenicillinAllergies


VancomycinTeicoplanin

GlycopeptideAntibioticsBacteriocidal

InhibitionoftheSynthesisofPeptidoglycanofBacterialCellWall

BindstoB-Ala-D-AlaTerminisofNascentPeptidoglycanPentapeptideSideChainandInhibitsTransglycosylation

PreventsElongationandCross-Linking**DoesNOTDependonBindingwithPBPstoProduce

Effect**------------------------WaterSoluble

PoorOralAbsorption(UsedforC.Diff)MostlyGivenIV

DoesNOTCrossBBB

MRSAGram+BacteriaOnly

Enterococci-----------------------------------------------

Vancomycin+Gentamycin:EnterococcalEndocarditis

ifPenicillinAllergies---------------------------------

Vancomycin+CefotaximeorCeftriaxone,orRifampin:

Penicillin-ResistantMeningitis

ExcretedbyGlomularFiltrationMustDecreaseDoseinRenalDysfunctionorToxicityMay

Occur-----------------

RedMan/RedNeckSyndrome:TypeIHSV

FlushingPruritusErythemaofHead/UpperBody

Hypotension(HISTAMINERELEASE)

Prevention:ProlongInfusionPeriodorAnti-HistaminePre-Treatment

-----------------------------------------Ototoxicity:

PermanentLossofHearing/Balance------------------------------------------------------------

Nephrotoxicity

Rare:VancomycinResistantStaphylococcusAureusandVancomycinResistantEnterococcalStrainsareRAREbut

Emerging(EspeciallyinSurgical/BurnUnits)---------------------------------------------

Mechanism:InvolvesaDecreasedAffinityforthe

BindingSiteDuetotheReplacememtoftheTerminalD-AlabyD-Lactate

--------------------------IfResistanceOccurs:

GiveLinezolid,Quinupristin,Dalfopristin

Fosfomycin GlycopeptideAntibioticsBacteriocidal

InhibitionofBacterialWallSynthesis

ActiveAgainstGram+andGram-Oral/ParenteralPrepsSAFEINPREGNANCY

UsedforUTIs

Bacitracin GlycopeptideAntibioticsBacteriocidal

TripleAntibioticComponentforSuppressionofMixedBacterialFlorainSurfaceLesionsoftheSkin,inWounds,

oronMucusMembranesTopicalApplication Nephrotoxicity

Daptomycin GlycopeptideAntibioticsBacteriocidal

SimilartoVancomycinBindstoCellMembraneViaCalcium-DependentInsertionofitsLipidTail,ResultinginDepolarizationoftheCellMembranewithPotassium

EffluxandRapidCellDeath

Skin/SoftTissueInfectionsBacteremiaEndocarditis

MyopathyAllergicPneumonitis

Keep Imipenum Lastin with Cilastin

When Others Fail, We Get the Job Done Broad Spectrum + Pseudomonas

Download - Drug Drug Class Mechanism of Action Indications Adverse ...€¦ · 2/12/2017 · Cell Wall Synthesis Inhibitors Bacteriocidal 4-Member Nitrogen Containing B-Lactam Ring Inhibit

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