antiviral farmasi

8/9/2019 Antiviral Farmasi

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UnderstandingViruses

Viruses do not fit the moldfor a living organismRange size from 10-450nanometers

Not grow unless cells wereadded to the growthmedium

They cannot make anythingon their own, they use thecells materials to build

themselvesOrigin: Speculated to berogue segments of DNAthat have taken a parasiticrole


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UnderstandingViruses

The Capsid: A protein shell of capsomer subunits. It hasthree purposes: to Shield,Attach, and Penetrate

The Envelope: Hybridcombination of cell lipids andvirus proteins, permitsattachment (note spikes)Nucleic Acids: Either DNA orRNA enclosed within the

capsid that is later used toreplicate more viruses withinthe host cell


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Understanding Viruses

Viral replication

A virus cannot replicate on its own

It must attach to and enter a host cell

It then uses the host cells energy to synthesizeprotein, DNA, and RNA


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Understanding Viruses

Viruses are difficult to kill becausethey live inside the cells

Any drug that kills a virus may also kill cells


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Antivirals Drugs

Viruses controlled by current antiviraltherapy

Cytomegalovirus (CMV)Hepatitis virusesHerpes virusesHuman immunodeficiency virus (HIV)Influenza viruses (the flu)Respiratory syncytial virus (RSV)


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Antivirals DrugsCharacteristics of antiviral drugs

Able to enter the cells infected with virus

Interfere with viral nucleic acid synthesis and/or regulation

Some drugs interfere with ability of virus to bind to cells

Some drugs stimulate the bodys immune system

Best responses to antiviral drugs are in patients withcompetent immune systems

A healthy immune system works synergistically with thedrug to eliminate or suppress viral activity


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Antiviral Medications

Antiviral drugsUsed to treat infections caused by viruses otherthan HIV

Antiretroviral drugsUsed to treat infections caused by HIV, the virusthat causes AIDS

Herpes-Simplex VirusesHSV-1 (oral herpes)HSV-2 (genital herpes)

Varicella Zoster VirusChickenpoxShingles


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Antiviral Drugs:Nonretroviral

Mechanism of actionInhibit viral replication

Used to treat non-HIV viralinfections

Influenza virusesHSV (herpes simplex virus), VZV (vericella zoster virus)CMV (cytomegalovirus)Hepatitis A, B, C (HAV, HBV, NCV)

Adverse Effects

Vary with each drugHealthy cells are often killed also, resulting in serioustoxicities


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Antivirals Drugs-NonretroviralAmantadine

Narrow antiviral spectrum active only against influenza A

Used prophylactically when vaccine is not available or cannotbe given

Therapeutic use can reduce recovery time

CNS effects : insomnia, nervousness, lightheadedness

GI effects : anorexia, nausea, others


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Antivirals Drugs-NonretroviralRimantadine

Same spectrum of activity, mechanismof action, and indications as amantadine

Fewer CNS adverse effects

Causes GI upset


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Antivirals Drugs-NonretroviralAcyclovir (Zovirax)

Synthetic nucleoside analog

Used to suppress replication of:HSV-1(oral herpes), HSV-2(genital herpes),VZV (Varicella chickenpox or shingles)

Drug of choice for treatment of initial andrecurrent episodes of these infections

Oral, topical, parenteral forms


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Antivirals Drugs-NonretroviralDose-Limiting Toxicities

ganciclovir and zidovudineBone marrow toxicity

foscarnet and cidofovirRenal toxicity


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Antivirals Drugs-NonretroviralNeuraminidase Inhibitors

oseltamivir (Tamiflu) and zanamivir (Relenza)Active against influenza types A & B

Use: Reduce duration of illness

oseltamivir : causes nausea & vomiting

zanamivir: causes diarrhea, nausea, sinusitis

Treatment should begin within 2 days of

influenza symptom onset


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Antivirals Drugs-NonretroviralRibavirin

Synthetic nucleoside analog

Given orally, or oral or nasal inhalation

Inhalation form (Virazole) used for

hospitalized infants with RSV (respiratorysyncytialvirus) infections


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HIVHuman immunodeficiency virus infection

ELISA (enzyme-linked immunosorbent assay)Detects HIV exposure based on presence of human antibodies to the virus inthe blood

RetrovirusTransmitted by:

Sexual activity, intravenous drug use, perinatally from mother to child

Five Stages of HIV Infection

Stage 1: asymptomatic infectionStage 2 : early, general symptoms of diseaseStage 3 : moderate symptomsStage 4 : severe symptoms, often leading to death

WHO model stages


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Antiretroviral Drugs

Reverse transcriptase inhibitors (RTIs)Block activity of the enzyme reverse transcriptase,preventing production of new viral DNA

Reverse transcriptase inhibitors (RTIs)Nucleoside RTIs (NRTIs)Nonnucleoside RTIs (NNRTIs)Nucleotide RTIs (NTRTIs)

Examples

abacavir (Ziagen) delavirdine (Rescriptor)didanosine (Videx) lamivudine (Epivir)stavudine (Zerit) tenofovir (Viread)


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Fusion inhibitors

Inhibit viral fusion, preventing viralreplication

Newest class of antiretroviral drugs

Example: enfuvirtide (Fuzeon)


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Combinations of multipleantiretroviral medications are common

Adverse effects vary with each drugand may be severe monitor for dose-limiting toxicities

Monitor for signs of opportunisticdiseases


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Antiretroviral Drugs:Adverse Effects

Numerousand vary with each drug

Drug

therapy may need to be modified because of adverse

effects

Goal is tofind the regimen that will best control the

infection with a tolerable adverse effect profile

Medication regimens change during the course of the illness


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Antifungal Agents


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Fungi (mycoses)

Mild or life threateningWidely present in environmentDermatophytestinea capitis, tineapedis, tinea cruris, tinea corporisExamples: Candida, Aspergillosis,Cryptococcus, Histoplasmosis, B


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Antifungal Drugs

Development of antifungals difficultbecause fungal cells closely resemblehuman cells

PolyenesAmphotericin B, NystatinAzolesSporonox (itraconazole), Nizoral(ketoconazole), Diflucan (fluconazole)

EchinocandinsEraxis (anidulafungin),Cancidas (caspofungin)


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Antifungal Drugs

Drugs acting on fungi

Block NucleicAcid Synthesis

FLUCYTOSINGRISEOFUL

VIN

DISRUPTMICROTUBULE

FUNCTION

ALTER CELLMEMBRANE

PERMEABILITY

AZOLE,POLYENES,

TERBINAFINE


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Amphotericin B ( POLYENEANTIBIOTIC)

Poorly absorbed from G I tract.Mechanism of action: effect on permeability andtransport system of fungal membranes. Bin toergosterol formation artificial pores.Clinical use: Systemic mycosisAdverse effects:

Infusion reaction with chills, fever, tachypnea Treat with Benadryl, Tylenol or steroids

Nephrotoxicity most serious SE


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Amphotericin B

Indicated for life-threatening fungalinfections such as aspergillosis,blastomycosis, candidiasis,

coccinioidomycosis, crytococcis andhistoplasmosisDrug concentrations are highest ininflamed tissues


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Nystatin

Same mechanism of action asAmphotericin B

Too toxic for systemic use


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Miscellaneous Antifungals

Lamisil (terbinafine)griseofulvin


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Azoles

Largest group of commonly usedantifungalsCan be used topically or systemically

Prototype is ketoconazoleFluconazole, itraconazole, VoriconazoleAll azoles are contraindicated in

pregnancy


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Azoles

Less toxic than amphoMany drug interactionsPoor absorption if achlorhydricSome hepatotoxicityCan be given orally


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fluconazole

Synthetic, broad spectrum againstcandidiasis, cryptococcis,coccidioidomycosis

Not effective against aspergillosisPO or IVFewer side effects than ketoconazole

Does not require gastric acidity, does notcross blood-brain barrierReduce dosage in renal failure


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itraconazole

Similar to Diflucan Drug of choice for blastomycosis,

histoplasmosis and sporotrichosis

Good for suppressive Tx in AIDS patientsw/histo Contraindicated for dermatophytic infections

and onychomycoses in heart failure patients IV or PO Many drug interactions


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griseofulvin

For dermatophyte infections of the scalpand nails and for extensive skineruptions

Drug binds to keratin, over time theinfected tissues are shed and replacedby uninfected tissues

Need 3-8 weeks to Tx ringwormUp to one year for onychomycoses


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terbinafine

Synthetic with broad spectrum of activityInhibits an enzyme needed for synthesisof ergosterol, a structural component of

fungal cell membranesGood for Tx of ringworm, nailshepatotoxic

D T f S ifi


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Drug Treatment for SpecificInfections

AspergillosisSporonox, Amphotericin BBlastomycosisSporonox, Amphotericin BCandidiasisvaries r/t area of infection

OralCutaneousVaginal

Systemic

D T t t f F l


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Drug Treatment for FungalInfections

HistoplasmosisSporanoxPCPBactrim, pentamidine, dapsone,others

Cryptococcis-Amphotericin BCoccidioidomycosis- azole toAmphotericin B

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