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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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Antiretroviral Drugs
Fusion inhibitors
Inhibit viral fusion, preventing viralreplication
Newest class of antiretroviral drugs
Example: enfuvirtide (Fuzeon)
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Antiretroviral Drugs
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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h (
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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