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Drug Drug Class Mechanism of Action Indications Adverse Effects Resistance Aminoglycosides 30S Ribosome Inhibitor Bacteriocidal Aminoglycoside Transport into Bacteria: Energy- Dependent (O2) Process: Aminoglycosides Actively Transported Across the Membrane of Aerobic Gram - Bacteria into the Cytoplasm --------------------------------------------------------- Transport May be Enhanced by Cell Wall Active Drugs (Penicillin/Vancomycin) ------------------------------- Aminoglycosides IRREVERSIBLY Bind to 30S They Interfere with the Initiation Complex of Peptide Formation (-Static) They Incorporate Incorrect Amino Acids into the Peptide, Resulting in Functional or Toxic Protein (-Cidal) Aerobic Gram- Rods -------------------------------------- Water Soluble Poor GIT Absorption PARENTERAL (IV/IM) ONLY Does NOT Cross BBB Single Daily Dose is Most Effective Exhibits Concentration-Dependent Killing and Post-Antibiotic Effect Nephrotoxic: Acute Tubular Necrosis Enhanced by: Amphotericin B, Vancomycin, Cisplatin, Cyclosporine ------------------------------------------------------------------------ Ototoxic: Auditory and Vestibular Damage (Hair Cell Damage) --------------------------------------------------------------------- Narrow Therapeutic Index Drug Monitoring for Renal Function (Dose Depedent) ---------- Neuromuscular Blockade: Curare-Like Effect with Respiratory Paralysis Muscle Tone is Lost Caution: Myasthenia Gravis Patients (Due to Decreased ACh Release) ---------------- Antidotes: Neostigmine Calcium Gluconates -------------------------------------------- Contact Dermatitis (Type IV): Neomycin Anaerobes are Innately Resistant ---------------------------------- Mechanisms: Inactivation by Acetylation, Adenylation, and Phoshphorylation: Plasmid-Mediated Synthesis of Enzymes that modify and inactive the antibiotic. Examples: Acetyl Transferases Nucleotidyltransferases Phosphotransferases ------------------------------------ Netilmicin/Amikacin: Less Vulnerable to these Enzymes --------------------------------------------------- Mechanisms: Impaired Entry Into the Cell: Mutations/Deleation of Porin Protein or O2 Transport Proteins ------------- Mutation of Receptor Protein on 30S Ribosome Streptomycin Aminoglycosides 30S Ribosome Inhibitor Bacteriocidal Same as Above Drug of Choice: Yersinia Pestis (Plague) Francisella Tularensis (Tularemia) --------------------------------------- Streptomycin + Penicillin G: Endocarditis (Enterococcal and Viridans) ------------------------------------------ Mycobacterium Tuberculosis Gentamicin Aminoglycosides 30S Ribosome Inhibitor Bacteriocidal Same as Above Pseudomonas Aeruginosa Klebsiella Proteus Serratia E. Coli Enterobacter Spp. --------------------------------------------- Penicillin/Vancomycin+ Gentamicin: Serious Enterococcal, Staphylococcal, S. Virdian Infections Amikacin Aminoglycosides 30S Ribosome Inhibitor Bacteriocidal Resistant to Aminoglycoside Inactivating Enzymes Expensive Reserved for when there is Gentamycin/Streptomycin Resistance Same Spectrum as Gentamicin ---------------------- More Potent: Pseudomonas Second Line: Tuberculosis Tobramycin Aminoglycosides 30S Ribosome Inhibitor Bacteriocidal Can be Inhaled (Cystic Fibrosis Patients) Same Spectrum as Gentamicin ---------------------- More Potent: Pseudomonas Paromomycin Aminoglycosides 30S Ribosome Inhibitor Bacteriocidal ONLY Aminoglycoside Active Against: Entamoeba Histolytica Cytosporidium Parvum Visceral Leishmaniasis Various Tapeworms (Solium) Neomycin Kanamycin Aminoglycosides 30S Ribosome Inhibitor Bacteriocidal Topical Use Neomycin + Bacitracin + Polymyxin: Triple Antibiotic Ointment Minor Soft Tissue Infections (Combined with Bacitracin/Polymyxin) ------------------------- Oral Neomycin: (Lactulose is DoC) Hepatic Encephalopathy and in Preparation for Elective Bowel Surgery (+Erythromycin) Limited Use Due to Toxicity Spectinomycin Spectinomycin 30S Ribosome Inhibitor Structurally Related to Aminoglycosides Alternative Treatment for Gonorrhea (Patients Allergic to Penicillins/Cephalorsporins) Not Available in USA Drug Drug Class Mechanism of Action Indications Adverse Effects Contraindications Tetracyclines 30S Ribosome Inhibitor Bacteriostatic Binds REVERSIBLY to 30S Subunit Blocks the Binding of Aminoacyl t-RNA to the Acceptor Site (A) on mRNA Ribosome Complex Prevents Addition of Amino Acids to the Growing Peptide ---------------------------------------------------------------------------- Oral Absorption is Impaired by: Chelation with Cations (Ca++, Mg++, Fe++, Al++) Dairy Food and Antacids Broad Spectrum Gram + and Gram - ------------------ Gram +: Streptococcus Gram - : Neisseria H. Pylori (BMT Regimen) H, Ducrei Brucella V. Cholera Atypical Bacteria: Chlamydia Riskettsiae Mycoplasma (DoC) Borrelia Burgdorferi Protozoa: Plasmodium Falciparum Entamoeba Histolytica Anaerobes: C. Perfringens C. Tetani Crosses Placenta: Bone Deformites/Tooth Dysplasias in the Fetus ------------------------------------------------------------------- GI Upset Tooth Enamel Dysplasia Decreased Bone Growth (Children) Renal: Fanconi Syndrome - Renal Damage Liver: Hepatotoxicity ------------------------------------------ Phototoxicity: Tetracycline, Demeclocycline, Doxycycline Other Drugs Causing Phototoxicity: Sulfonamides, Fluroquinolines ----------------------------------- Effects on Intestinal Microflora: Occurance of Superinfections (C. Diff, Pseudomonas, Proteus, Yeasts) Pseudomembranous Colitis Pregnancy Prepubertal Children (<8) Serious Hepatic/Renal Diseases (Doxycycline is used in Renal Disease) Cannot use in IM Injections (Causes Pain and Inflammation) IV and Oral ONLY -------------------------------- Resistance: Plasmid Mediated Efflux Pump Large Resistance Doxycyline Tetracyclines 30S Ribosome Inhibitor Bacteriostatic Completely Absorbed Eliminated by Liver (Used in Kidney Dysfunction) Given Twice Daily Is NOT Significantly Affected by Food Drug of Choice: All Atypical!! Chlamydial Infections (Urethritis, PID, Cervicitis, Etc) Rickettsiae Mycoplasma Pneumonia Borrelia Burgdorferi Oral Given Twice Daily Absorption NOT Affected by Food

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Page 1: Drug Drug Class Mechanism of Action Indications Adverse ... · 12/3/2017  · Antidotes: Neostigmine ... Examples: Acetyl Transferases Nucleotidyltransferases Phosphotransferases

Drug DrugClass MechanismofAction Indications AdverseEffects Resistance

Aminoglycosides30SRibosomeInhibitor

Bacteriocidal

AminoglycosideTransportintoBacteria:Energy-Dependent(O2)Process:AminoglycosidesActivelyTransportedAcrosstheMembraneofAerobicGram-

BacteriaintotheCytoplasm---------------------------------------------------------

TransportMaybeEnhancedbyCellWallActiveDrugs(Penicillin/Vancomycin)-------------------------------

AminoglycosidesIRREVERSIBLYBindto30STheyInterferewiththeInitiationComplexofPeptide

Formation(-Static)TheyIncorporateIncorrectAminoAcidsintothePeptide,

ResultinginFunctionalorToxicProtein(-Cidal)

AerobicGram-Rods--------------------------------------

WaterSolublePoorGITAbsorption

PARENTERAL(IV/IM)ONLYDoesNOTCrossBBB

SingleDailyDoseisMostEffectiveExhibitsConcentration-DependentKillingandPost-AntibioticEffect

Nephrotoxic:AcuteTubularNecrosisEnhancedby:

AmphotericinB,Vancomycin,Cisplatin,Cyclosporine------------------------------------------------------------------------

Ototoxic:AuditoryandVestibularDamage(HairCellDamage)

---------------------------------------------------------------------NarrowTherapeuticIndex

DrugMonitoringforRenalFunction(DoseDepedent)----------

NeuromuscularBlockade:Curare-LikeEffectwithRespiratoryParalysis

MuscleToneisLostCaution:

MyastheniaGravisPatients(DuetoDecreasedAChRelease)

----------------Antidotes:Neostigmine

CalciumGluconates--------------------------------------------

ContactDermatitis(TypeIV):Neomycin

AnaerobesareInnatelyResistant----------------------------------

Mechanisms:InactivationbyAcetylation,Adenylation,

andPhoshphorylation:Plasmid-MediatedSynthesisofEnzymesthatmodifyandinactivetheantibiotic.

Examples:AcetylTransferases

NucleotidyltransferasesPhosphotransferases

------------------------------------Netilmicin/Amikacin:

LessVulnerabletotheseEnzymes---------------------------------------------------

Mechanisms:ImpairedEntryIntotheCell:

Mutations/DeleationofPorinProteinorO2TransportProteins

-------------MutationofReceptorProteinon30S

Ribosome

StreptomycinAminoglycosides

30SRibosomeInhibitorBacteriocidal

SameasAbove

DrugofChoice:YersiniaPestis(Plague)

FrancisellaTularensis(Tularemia)---------------------------------------Streptomycin+PenicillinG:

Endocarditis(EnterococcalandViridans)

------------------------------------------MycobacteriumTuberculosis

GentamicinAminoglycosides

30SRibosomeInhibitorBacteriocidal

SameasAbove

PseudomonasAeruginosaKlebsiellaProteusSerratiaE.Coli

EnterobacterSpp.---------------------------------------------

Penicillin/Vancomycin+Gentamicin:Serious

Enterococcal,Staphylococcal,S.VirdianInfections

AmikacinAminoglycosides

30SRibosomeInhibitorBacteriocidal

ResistanttoAminoglycosideInactivatingEnzymesExpensive

ReservedforwhenthereisGentamycin/StreptomycinResistance

SameSpectrumasGentamicin----------------------

MorePotent:PseudomonasSecondLine:Tuberculosis

TobramycinAminoglycosides

30SRibosomeInhibitorBacteriocidal

CanbeInhaled(CysticFibrosisPatients)SameSpectrumasGentamicin

----------------------MorePotent:Pseudomonas

ParomomycinAminoglycosides

30SRibosomeInhibitorBacteriocidal

ONLYAminoglycosideActiveAgainst:EntamoebaHistolyticaCytosporidiumParvumVisceralLeishmaniasis

VariousTapeworms(Solium)

NeomycinKanamycin

Aminoglycosides30SRibosomeInhibitor

Bacteriocidal

TopicalUseNeomycin+Bacitracin+Polymyxin:

TripleAntibioticOintment

MinorSoftTissueInfections(CombinedwithBacitracin/Polymyxin)

-------------------------OralNeomycin:(LactuloseisDoC)

HepaticEncephalopathyandinPreparationforElectiveBowelSurgery

(+Erythromycin)

LimitedUseDuetoToxicity

Spectinomycin Spectinomycin30SRibosomeInhibitor

StructurallyRelatedtoAminoglycosidesAlternativeTreatmentforGonorrhea

(PatientsAllergictoPenicillins/Cephalorsporins)

NotAvailableinUSA

Drug DrugClass MechanismofAction Indications AdverseEffects Contraindications

Tetracyclines30SRibosomeInhibitor

Bacteriostatic

BindsREVERSIBLYto30SSubunitBlockstheBindingofAminoacylt-RNAtotheAcceptorSite(A)onmRNARibosomeComplex

PreventsAdditionofAminoAcidstotheGrowingPeptide----------------------------------------------------------------------------

OralAbsorptionisImpairedby:ChelationwithCations(Ca++,Mg++,Fe++,Al++)

DairyFoodandAntacids

BroadSpectrumGram+andGram-------------------

Gram+:StreptococcusGram-:Neisseria

H.Pylori(BMTRegimen)H,DucreiBrucellaV.Cholera

AtypicalBacteria:ChlamydiaRiskettsiae

Mycoplasma(DoC)BorreliaBurgdorferi

Protozoa:PlasmodiumFalciparumEntamoebaHistolytica

Anaerobes:C.Perfringens

C.Tetani

CrossesPlacenta:BoneDeformites/ToothDysplasiasintheFetus

-------------------------------------------------------------------GIUpset

ToothEnamelDysplasiaDecreasedBoneGrowth(Children)

Renal:FanconiSyndrome-RenalDamageLiver:Hepatotoxicity

------------------------------------------Phototoxicity:

Tetracycline,Demeclocycline,DoxycyclineOtherDrugsCausingPhototoxicity:

Sulfonamides,Fluroquinolines-----------------------------------

EffectsonIntestinalMicroflora:OccuranceofSuperinfections

(C.Diff,Pseudomonas,Proteus,Yeasts)PseudomembranousColitis

PregnancyPrepubertalChildren(<8)

SeriousHepatic/RenalDiseases(DoxycyclineisusedinRenalDisease)

CannotuseinIMInjections(CausesPainandInflammation)

IVandOralONLY--------------------------------

Resistance:PlasmidMediatedEffluxPump

LargeResistance

DoxycylineTetracyclines

30SRibosomeInhibitorBacteriostatic

CompletelyAbsorbedEliminatedbyLiver(UsedinKidneyDysfunction)

GivenTwiceDailyIsNOTSignificantlyAffectedbyFood

DrugofChoice:AllAtypical!!ChlamydialInfections

(Urethritis,PID,Cervicitis,Etc)Rickettsiae

MycoplasmaPneumoniaBorreliaBurgdorferi

OralGivenTwiceDaily

AbsorptionNOTAffectedbyFood

Page 2: Drug Drug Class Mechanism of Action Indications Adverse ... · 12/3/2017  · Antidotes: Neostigmine ... Examples: Acetyl Transferases Nucleotidyltransferases Phosphotransferases

TetracyclineTetracyclines

30SRibosomeInhibitorBacteriostatic

EliminatedbyLiver(UsedinKidneyDysfunction)

DemeclocyclineTetracyclines

30SRibosomeInhibitorBacteriostatic

DiabetesInsipitus

MinocyclineTetracyclines

30SRibosomeInhibitorBacteriostatic

CompletelyAbsorbedEnterstheBrain

AppearsinTears/Saliva

UsefulinEradicatingMeningococcalCarrierState

(RifampinisPREFERRED)

Tigecycline Glycylcyclines SameasTetracyclines

SlowIVInfusionEliminatedbyLiver

Broad-SpectrumActivityMRSADRUG

Vancomycin-ResistantEnterococciDrug

Drug DrugClass MechanismofAction Indications AdverseEffects Contraindications

ErythromycinClarithromycinAzithromycinRoxithromycin

Macrolides50SRibosomeInhibitor

Bacteriostatic

LactoneRingwithDeoxySugarsAttached-------------------

ProteinSynthesisInhibitors:IRREVERSIBLYBindto50SSubunitofBacterialRibosomeandInhibittheTranslocationStepofProteinSynthesis------------------------------------------------------------------------

AllShouldbeTakeonanEmptyStomach(LikeTetracyclines)

UsedinPatientsAllergictoB-LactamAntibiotics(Penicillins)

Gram+Infections

EpigastricDistress:(MorewithErythromycin)GITProblems(MostCommon)

CholestaticJaundice(withEstolate)------------------------ProkineticAction:

MacrolidesBindwithMotilinReceptorsinGIT

IncreasesIntestinalMotility(Diarrhea)---------------------------------

ProlongQTIntervalandArrhythmias

HepaticDysfunction--------------------------------

DrugInteractions:ErythromycinandClarithromycin:

InhibitCYP450EnzymesInhibitMetabolismof:

TheophyllineWarfarinCyclosporineMethylprednisolone------------------------

INCREASELevelsofDigoxin:ByInhibitingitsInactivationinthe

Intestine---------------------------------------------------

MechanismsofResistance:DecreasedAffinityofthe50SRibosomal

SubunitGram+Bacteria:

ProducesMethylase, thatAddsaMethylGroup(RibosomalProtection)PresenceofPlasmidAssociated

ErythromycinEsterase(HydrolyzesMacrolides)

InabilitytoPenetrate/IncreasedEffluxCross-ResistanceisCompleteBetweenErythromycinandOtherMacrolides.

ErythromycinMacrolides

50SRibosomeInhibitorBacteriostatic

Classic**PoorBiovailabilityFrequentDosingGIIrritability

LimitedH.InfluenzaeCoverage**-------------------------------------------------------

AcidLabileAdministeredinEntericCoating

DoesNOTCrossBBBInhibitsManyCYP450Enzymes

ExcretedPrimarilyinBile(GoodforRenalFailurePatients)

Gram+Cocci(NotMRSA)CorynebacteriumDiptheriae

Gram-:Gonorrhea,Legionella,BordetellaPertussisAtypicalOrganisms:

Mycoplasma,Chlamydia,Ureaplasma,Campylobacter,Spirochetes,H.Pylori,Listeria

Monocytogenes

HigherGIIntolerance

ClarithromycinMacrolides

50SRibosomeInhibitorBacteriostatic

*SyntheticOvercomesErythromycinLimitations(Above)*---------------------------------

InhibitsManyCYP450EnzymesExcretedPrimarilyinBile

GreaterActivityAgainst:M.AviumH.Pylori

ToxoplasmaGondiiH.Influenza

LowerGIIntolerance

AzithromycinMacrolides

50SRibosomeInhibitorBacteriostatic

*SyntheticOvercomesErythromycinLimitations(Above)*DOESNOTINHIBITCYP450GiveOnlyONCEPerDay

MoreActiveinRespiratoryInfections(H.Influenza,Moraxella,

MycobacteriumAvium,Chlamydia)-----------------------------

CommunityAcquiredPneumoniaPharyngitis

ChlamydialInfectionsSkinInfections

ExcretedbyKIDNEYMoreToleratedinPregnancy

RoxithromycinMacrolides

50SRibosomeInhibitorBacteriostatic

Drug DrugClass MechanismofAction Indications AdverseEffects Resistance

Clindamycin Bacteriostatic NotaMacrolideBUTHasSameMechanism

TreatmentofSkinandSoftTissueInfectionsStreptocociStaphylococci

BacteroidesFragilis----------------

ProphylaxisofEndocarditisinPatientswithValvularHeartDiseasewhoareUndergoingCertainDentalProcedures

andhavePenicillinAllergies(RecommendedoverErythromycin)

-----------------------Clindamycin+Primaquine:AlternativeMedication

P.JiroveciPneumoniainAIDS------------------------------------

Clindamycin+Pyrimethamine:Toxoplasmosis(Brain)inAIDS

NauseaDiarrhea

SkinRashesPseudomembranousColitis-------------------------------

C.DiffisResistanttoClindamycin----------------------------------------------------ImpairedLiverFunctionandNeutropenia

Drug DrugClass MechanismofAction Indications AdverseEffects Resistance

Ear Infections

Page 3: Drug Drug Class Mechanism of Action Indications Adverse ... · 12/3/2017  · Antidotes: Neostigmine ... Examples: Acetyl Transferases Nucleotidyltransferases Phosphotransferases

Chloramphenicol Bacteriostatic

BindsReversiblytothe50SSubunitPreventsPeptidyltransferaseEnzymefromTransferring

theGrowingChainfromthe"P"SitetotheBoundChargedtRNAatthe"A"Site.

--------------------------OralAdministration

Rapidly/CompletelyAbsorbedDoesCrossBBB

MetabolizedtoGlucuronideConjugatebytheLiver

BroadSpectrum(AllAlternative)BacteroidesBFragilis

H.InfluenzaeMeningococcalMeningitis

(N.Meningitis)ClostridiaRickettsiaeMycoplasma

TyphoidFever(Salmonella)-------------------------NOTChlamydia-----------------

UsedTopicallyinTreatmentofEyeInfections

(PenetratesOcularTissuesandAqueousHumor)

CanAntagonizeBacteriocidalDrugs(PenicillinsandAminoglycosides)

--------------------------GIUpset

BoneMarrowSuppression(AplasicAnemia)Oral/VaginalCandidiasisGrayBabySyndrome:

MainlyinPrematureNeonatesNewbornsLackEffectiveGlucuronideConjugationand

DetoxificationMechanism.Doses>50mg/mg/dayCauses:

VomitingFaccidity

HypothermiaGrayColorShock

VascularCollapse

Resistance:ProductionofAcetyltransferasesCapable

ofInactivatingtheDrug-------------------------------------------------------

DrugInteractions:InhibitsCYP450(OxidaseEnzymes):

ProlongsHalfLifeof:PhenytoinCoumarin

Tolbutamide

Linezolid SyntheticOxazolidinone

Bindsto50SSubunitInhibitsBacterialProteinSynthesisbyInhibitingthe

Formationof70SInitationComplex(N-Formylmethionyl-tRNA-ribosome-mRNATernaryComplex)

RecentlyIntroducedCombatsResistantGram+

VRSAandVREDrugResistantPneumococci

MycobacterialTuberculosis

NocardiaInfections

ThrombocytopeniaAnemiaandNeutropenia------------------------------------

IfGivenwithSSRIs:SerotoninSyndrome

QuinupristinDalfopristin Streptogramins

EachComponentBindstoaSeparateSiteonthe50SSubunitandSynergisticallyInterruptsProteinSynthesis

UsedasaMixture(30:70)VRSA

VRE(E.FaeciumOnly)(NotEffectiveAgainstEnterococcus

Faecalis)

Infusion-RelatedEvents:PainArthralgia-MyalgiaSyndrome


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