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Steps: Attachment Penetration Uncoating Replication Assembly Release Drug Drug Class Mechanism of Action Indications Adverse Effects Resistance Docosanol (Abreva) HSV Drug Aliphatic Alcohol Inhibits Fusion Between Host Cell Plasma Membrane and HSV Envelope Topical Agent for HSV Idoxuridine Trifluridine HSV Drug Thymidine Analogs Triphosphorylated to Active Drugs that Inhibit DNA Polymerase Topical (Opthalmic Use) HSV Retinitis Poor Systemic Absorption ---------- Trifluridine: Acyclovir-Resisant HSV Infections Acyclovir Herpes Virus Infection Drug Clovirs: Guanine Analogues with Anti-Viral Activity Against ONLY Herpes Viruses Triphosphorylated to Active Drugs ----------------------------------- Cleared by GFR & Tubular Secretion T1/2 Depends on Renal Function HSV-1/2: Treatment and Prophylaxis Genital/Mucocutaneous Herpes ------- H.Simplex Encephalitis (HSV-1) H. Simplex Keratitis (HSV-1) -------- Herpes Zoster (VZV): Shingles Chicken Pox (VZV): Children ----------------- Varicella (VZV) Epstein Barr Virus (EBV) -------------------------- CMV is Resistant -------------------------- Poor Oral Absorption Few Most Frequently: Renal Dysfunction ----------------------- Occasional: GIT: Nausea, Vomiting, Diarrhea CNS: Tremors Lethargy ------------------- IV Administration: Infusion Site Phlebitis/Inflammation (Extravasation) Reversible Kidney Dysfunction due to Crystalline Nephropathy Acyclovir Resistance: In HSV/VZV: Mutation in Viral Thymidine Kinase --> Deficiency in Thymidine Kinase Activity --> Cross Resistance with All Other Clovirs OR DNA Polymerase Mutation ---------------------------------------------- Resistant HSV Isloates in HIV-Positive Patients Assocated With: Chronic Cutaneous Lesions and Invasive Disease (Rarely) Valacyclovir Famciclovir Penciclovir Herpes Virus Infection Drug Clovirs: Guanine Analogues with Anti-Viral Activity Against ONLY Herpes Viruses Triphosphorylated to Active Drugs ----------------------------------- Pro-Drugs: Valacyclovir --> Acyclovir (Prolonged Release) Famciclovir --> Penclovir Pencyclovir: Not Absorbed Orally Similar Activity to Acyclocvir Achieves Higher Intracellular Levels Varicella Zoster (VZV) Herpes Simplex (HSV) Cidofovir: Also Effective for Adenoviruses Same as Above Acyclovir Resistance: In HSV/VZV: Mutation in Viral Thymidine Kinase --> Deficiency in Thymidine Kinase Activity --> Cross Resistance with All Other Clovirs OR DNA Polymerase Mutation ---------------------------------------------- Resistant HSV Isloates in HIV-Positive Patients Assocated With: Chronic Cutaneous Lesions and Invasive Disease (Rarely) Foscarnet Herpes Virus Infection Drug Tri-Sodium Salt of Phosphonoformate (Inorganic Pyrophosphate) ----------------------------------------------------------------- Specifically Inhibits Viral DNA Polymerase and RNA Polymerase and HIV Reverse Transcriptase by Competing for the Pyrophosphate Binding Site Drug of Choice: Acyclovir-Resistant HSV or VZV Infections -------------------------------- Immunocompromised with CMV Retinitis Mucocutaneous Acyclovir-Resistant HSV Infections Renal Impairment (Major Toxicity) --> Hypokalemia, Hypomagnesemia, Hypocalcemia Resistance: Mutations in CMV UL54 Gene, which Encodes for DNA Polymerase Ganciclovir Cytomegalovirus Infection Drugs (CMV) Gaunosine Analog: Activated via Phosphorylation ------------------------- In CMV Infected Cells, Initial Phosphorylation is by Virus- Specific Kinase (UL97), then 2x by Host Kinase -------- Activated Triphosphate Inhibits Viral DNA Polymerase and Terminates Viral DNA Elongation Has In Vitro Activity Against: CMV HSV VZV EBC HHV-6 HHV-8 -------------------------------- CMV Retinitis/Prophylaxis (Oral, IV, Inraocular Implant) Valganciclovir Cytomegalovirus Infection Drugs (CMV) Prodrug: Metabolized to Ganciclovir Much Higher Bioavailability Oral CMV Retinitis CMV Prophylaxis (Transplant Patients) See Above Foscarnet Cytomegalovirus Infection Drugs (CMV) See Above CMV Retinitis (IV) See Above Cidofovir Cytomegalovirus Infection Drugs (CMV) See Above CMV Retinitis (IV) See Above Drug Drug Class Mechanism of Action Indications Adverse Effects Resistance Amantadine Rimantadine Influenza Virus Infection Drugs Prevents Uncoating of Influenza A Binds to M-2 Protein (Ion Channel Promoting Budding of Mature Virus) -------------------------- Appear to be Virustatic Affect Maturation of Influenza HA Glycoprotein in Trans- Golgi Network Not Used in USA (Resistance) Influenza A Prophylaxis and Early Treatment Amantadine > Rimantadine Occurs More in Elderly Patients GI: Nausea CNS: Lightheadedness, Insomnia Resistance is Common Mutations of the M-2 Protein Oseltamivir Zanamivir Influenza Virus Infection Drugs Selectively Inhibits Viral Neuraminidases Prevents Virion Release Oseltamivir: Pro-Drug Activated in Liver Influenza A + B (Includes H1N1, H5N1) Prophylaxis and Early Treatment Oseltamivir Toxicity: GI Distrurbance Zanamivir Toxicity: Bronchospasm Vral Neuraminidase Mutations Drug Drug Class Mechanism of Action Indications Adverse Effects Resistance Interferon Viral Hepatitis B Infection Drugs Glycoprotein Produced Naturally by Different Cells in the Immune System after Exposure to Viruses ------------------------------------ Increases Activity of JAK-STAT Pathway Induces Up-Regulation of Anti-Viral Proteins --------- Binds to Cell Surface Receptor Induces Expression of Translation Inhibitory Protein (TIP) TIP Binds to Ribosome Inhibits Expression of Viral Proteins ---------------------------------------------------------- General Classes: Alpha, Beta, Gamma Administration: Parenteral Only (IV, SQ, Nasal Spray) -------------------------------- Broad Spectrum DNA Viruses: Chronic Hepatitis B HSV-1/2 and Herpes Zoster HPV (Genital Warts) ----- RNA Viruses: Chronic Hepatitis C Influenza (Common Cold) Breast Cancer Lung Cancer Kaposi's Sarcoma (AIDS Patients) Flu-Like Symptoms (Headache, Fatigue, Anthralgias, Fever, Chills) Depression, Insomnia Alopecia Thyroiditis: Can Unmask or Exacerbate (May Not be Reversible after Stopping Treatment)

Drug Drug Class Mechanism of Action Indications Adverse Effects … · 2017-12-06 · Pencyclovir: Not Absorbed Orally Similar Activity to Acyclocvir Achieves Higher Intracellular

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Page 1: Drug Drug Class Mechanism of Action Indications Adverse Effects … · 2017-12-06 · Pencyclovir: Not Absorbed Orally Similar Activity to Acyclocvir Achieves Higher Intracellular

Steps:AttachmentPenetrationUncoatingReplicationAssemblyRelease

Drug DrugClass MechanismofAction Indications AdverseEffects ResistanceDocosanol(Abreva) HSVDrug

AliphaticAlcoholInhibitsFusionBetweenHostCellPlasmaMembraneand

HSVEnvelopeTopicalAgentforHSV

IdoxuridineTrifluridine HSVDrug

ThymidineAnalogsTriphosphorylatedtoActiveDrugsthatInhibitDNA

Polymerase

Topical(OpthalmicUse)HSVRetinitis

PoorSystemicAbsorption----------

Trifluridine:Acyclovir-ResisantHSVInfections

Acyclovir HerpesVirusInfectionDrug

Clovirs:GuanineAnalogueswithAnti-ViralActivityAgainstONLY

HerpesVirusesTriphosphorylatedtoActiveDrugs

-----------------------------------ClearedbyGFR&TubularSecretionT1/2DependsonRenalFunction

HSV-1/2:TreatmentandProphylaxis

Genital/MucocutaneousHerpes-------

H.SimplexEncephalitis(HSV-1)H.SimplexKeratitis(HSV-1)

--------HerpesZoster(VZV):ShinglesChickenPox(VZV):Children

-----------------Varicella(VZV)

EpsteinBarrVirus(EBV)--------------------------CMVisResistant

--------------------------PoorOralAbsorption

FewMostFrequently:RenalDysfunction-----------------------

Occasional:GIT:Nausea,Vomiting,Diarrhea

CNS:TremorsLethargy-------------------

IVAdministration:InfusionSitePhlebitis/Inflammation(Extravasation)ReversibleKidneyDysfunctionduetoCrystalline

Nephropathy

AcyclovirResistance:InHSV/VZV:

MutationinViralThymidineKinase-->DeficiencyinThymidineKinaseActivity-->CrossResistancewithAllOtherClovirs

ORDNAPolymeraseMutation

----------------------------------------------ResistantHSVIsloatesinHIV-Positive

PatientsAssocatedWith:ChronicCutaneousLesionsand

InvasiveDisease(Rarely)

ValacyclovirFamciclovirPenciclovir

HerpesVirusInfectionDrug

Clovirs:GuanineAnalogueswithAnti-ViralActivityAgainstONLY

HerpesVirusesTriphosphorylatedtoActiveDrugs

-----------------------------------Pro-Drugs:

Valacyclovir-->Acyclovir(ProlongedRelease)Famciclovir-->Penclovir

Pencyclovir:NotAbsorbedOrally

SimilarActivitytoAcyclocvirAchievesHigherIntracellularLevels

VaricellaZoster(VZV)HerpesSimplex(HSV)

Cidofovir:AlsoEffectiveforAdenoviruses

SameasAbove

AcyclovirResistance:InHSV/VZV:

MutationinViralThymidineKinase-->DeficiencyinThymidineKinaseActivity-->CrossResistancewithAllOtherClovirs

ORDNAPolymeraseMutation

----------------------------------------------ResistantHSVIsloatesinHIV-Positive

PatientsAssocatedWith:ChronicCutaneousLesionsand

InvasiveDisease(Rarely)

Foscarnet HerpesVirusInfectionDrug

Tri-SodiumSaltofPhosphonoformate(InorganicPyrophosphate)

-----------------------------------------------------------------SpecificallyInhibitsViralDNAPolymeraseandRNA

PolymeraseandHIVReverseTranscriptasebyCompetingforthePyrophosphateBindingSite

DrugofChoice:Acyclovir-ResistantHSV

orVZVInfections--------------------------------

ImmunocompromisedwithCMVRetinitis

MucocutaneousAcyclovir-ResistantHSVInfections

RenalImpairment(MajorToxicity)-->Hypokalemia,Hypomagnesemia,Hypocalcemia

Resistance:MutationsinCMVUL54Gene,which

EncodesforDNAPolymerase

Ganciclovir CytomegalovirusInfectionDrugs(CMV)

GaunosineAnalog:ActivatedviaPhosphorylation-------------------------

InCMVInfectedCells,InitialPhosphorylationisbyVirus-SpecificKinase(UL97),then2xbyHostKinase

--------ActivatedTriphosphateInhibitsViralDNAPolymerase

andTerminatesViralDNAElongation

HasInVitroActivityAgainst:CMVHSVVZVEBCHHV-6HHV-8

--------------------------------CMVRetinitis/Prophylaxis(Oral,IV,InraocularImplant)

Valganciclovir CytomegalovirusInfectionDrugs(CMV)

Prodrug:MetabolizedtoGanciclovirMuchHigherBioavailability

OralCMVRetinitis

CMVProphylaxis(TransplantPatients)SeeAbove

Foscarnet CytomegalovirusInfectionDrugs(CMV)

SeeAbove CMVRetinitis(IV) SeeAbove

Cidofovir CytomegalovirusInfectionDrugs(CMV)

SeeAbove CMVRetinitis(IV) SeeAbove

Drug DrugClass MechanismofAction Indications AdverseEffects Resistance

AmantadineRimantadine InfluenzaVirusInfectionDrugs

PreventsUncoatingofInfluenzaABindstoM-2Protein

(IonChannelPromotingBuddingofMatureVirus)--------------------------

AppeartobeVirustaticAffectMaturationofInfluenzaHAGlycoproteininTrans-

GolgiNetwork

NotUsedinUSA(Resistance)InfluenzaA

ProphylaxisandEarlyTreatment

Amantadine>RimantadineOccursMoreinElderlyPatients

GI:NauseaCNS:Lightheadedness,Insomnia

ResistanceisCommonMutationsoftheM-2Protein

OseltamivirZanamivir InfluenzaVirusInfectionDrugs

SelectivelyInhibitsViralNeuraminidasesPreventsVirionRelease

Oseltamivir:Pro-DrugActivatedinLiver

InfluenzaA+B(IncludesH1N1,H5N1)

ProphylaxisandEarlyTreatment

OseltamivirToxicity:GIDistrurbanceZanamivirToxicity:Bronchospasm

VralNeuraminidaseMutations

Drug DrugClass MechanismofAction Indications AdverseEffects Resistance

Interferon ViralHepatitisBInfectionDrugs

GlycoproteinProducedNaturallybyDifferentCellsintheImmune

SystemafterExposuretoViruses------------------------------------

IncreasesActivityofJAK-STATPathwayInducesUp-RegulationofAnti-ViralProteins

---------BindstoCellSurfaceReceptor

InducesExpressionofTranslationInhibitoryProtein(TIP)TIPBindstoRibosome

InhibitsExpressionofViralProteins----------------------------------------------------------

GeneralClasses:Alpha,Beta,Gamma

Administration:ParenteralOnly(IV,SQ,NasalSpray)

--------------------------------BroadSpectrumDNAViruses:

ChronicHepatitisBHSV-1/2andHerpesZoster

HPV(GenitalWarts)-----

RNAViruses:ChronicHepatitisC

Influenza(CommonCold)BreastCancerLungCancer

Kaposi'sSarcoma(AIDSPatients)

Flu-LikeSymptoms(Headache,Fatigue,Anthralgias,Fever,Chills)

Depression,InsomniaAlopecia

Thyroiditis:CanUnmaskorExacerbate(MayNotbeReversibleafterStoppingTreatment)

Page 2: Drug Drug Class Mechanism of Action Indications Adverse Effects … · 2017-12-06 · Pencyclovir: Not Absorbed Orally Similar Activity to Acyclocvir Achieves Higher Intracellular

Ribavirin ViralHepatitisBInfectionDrugs

Pro-Drug:GuanosineAnalogActivated(Phosphorylated)byHost

KinasesviaPhosphorylationtoActiveMetabolite-----------------------------------

InterfereswithSynthesisofGTPInhibitsViralRNA-DependentDNAPolymeraseandCappingofViralmRNA

-------------------------------UsesTriphosphatetoInhibitReplicationofBothDNAand

RNAViruses

UsedinCombinationwithInterferon----------------------InfluenzaA+BParainfluenzaDoC:RSV

ParamyxovirusesHCVHIV-1

Lamivudine ViralHepatitisBInfectionDrugsNucleosideAnalogInhibitsHBVDNAPolymerase

-------AlsoInhibitsHIVReverseTranscriptase

HIV/HBVCo-Infection Well-Tolerated RapidEmergencyofDrugResistance

Adefovir ViralHepatitisBInfectionDrugs

AdenineNucleotideAnalog:PhosphorylatedbyCellularKinasestoActiveDiphosphateMetabolite-->

CompetitivelyInhibitsHBVDNAPolymeraseandCausesChainTerminationafterIncorporationintoViralDNA

BroadSpectumHBVHIV

HerpesViruses------------------------------

UsedtoTreatLamivudine-ResistantHBV

MoreExpensiveandToxicthanLamivudineLessLikelytoDevelopResistancethan

Lamivudine

Entecavir ViralHepatitisBInfectionDrugs

GuanosineNucleosideAnalogSimilartoAdefovir-------------

CompetitivelyInhibitsAll3FunctionsofHBV:1.DNAPolymerase,IncludingBasePriming

2.ReverseTranscriptionoftheNegativeStrand3.SynthesisofthePositiveStrandofHBVDNA

PowerfulAnti-Viral100%OralBioavailability

------ResultsinDisappearanceofHBsAg,HBV-DNA,andSeroconversionto

Hbe-Ag-Negative

Interferon+Ribavirin ViralHepatitisCInfectionDrugs

Sofosbuvir ViralHepatitisCInfectionDrugs NucleotideInhibitorofHCVRNANS5BPolymerase

VeryHighCureRates----------------------ChronicHepatitisC(Genotype1,2,3,4)

GiveOD(WithPeginterferonAlfa+Ribavirin)

PancytopeniaSuicidalIdeation

DiarrheaAnemiaHeadacheInsomniaFatigue

Contraindicated:PregnanctWomenandMenwith

PregnantFemalePartners

BoceprevirSimeprevirTelaprevir

ViralHepatitisCInfectionDrugs ProteaseInhibitors Co-AdministerwithRibavirinContraindicated:

PregnanctWomenandMenwithPregnantFemalePartners

Hemolytic Anemia


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