DA Antiviral Agents I

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HUSOP2014
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136898
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DA Antiviral Agents I
Updated:
2012-02-22 07:36:28
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HUSOP DA EXAM2 antiviral
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2-13-12 Lecture
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  1. Why are antiviral agents difficult to develop


    Because viruses use host cell machinery and theyhave toxicities when tested in vivo.
  2. Identify the correct sequence of events from
    beginning to end


    a. Cell entry>transcription of viral genome>translation
    of viral proteins>post-translational
    modifications>release>uncoating>assembly of virion components

    b. Cell entry>uncoating>transcription of
    viral genome>translation of viral proteins>post-translational
    modifications>assembly of virion components>release

    c. Cell entry>uncoating>transcription of
    viral genome>translation of viral proteins>post-translational
    modifications>release>assembly of virion components
    B
  3. Effective antiviral agents target
    ________
    Viral proteins
  4. Current agents will not eliminate
    ________ viruses
    Nonreplicating or latent
  5. Antiviral resistance occurs
    maximally in ____________ patients with high viral load and prolonged therapy
    Immune-compromised
  6. T or F Most antiviral therapies are able to
    destroy non-replicating viruses.
    False
  7. HSV __ causes infection of genitals, rectum
    skin, hands, meninges while HSV __ causes infection of mouth, face, skin,
    esophagus or brain.
    2, 1
  8. HSV is _______, meaning it is sequestered in
    nerve cells until reactivation moves virus to the skin.
    neurotropic
  9. Clicker question: Viral
    immediate-early genes code for what?


    Viral proteins for genome replication
  10. In a HSV virus the ______
    surrounds the DNA.
    nucleocapsid
  11. Which of the following CANNOT reactivate a
    latent HSV infection: eczema, gastric upset, fungal infection, bright sunlight.
    fungal infection
  12. What HSV enzyme phosphorylates
    acyclovir first?
    HSV thymidine kinase
  13. The final active metabolite of
    acyclovir is acyclovir ________
    Triphosphate
  14. Is acyclovir a competitive inhibitor
    or noncompetitive inhibitor?
    Noncompetitive
  15. T/F: Acyclovir-TP acts to inhibit
    viral polymerase AND acts as a chain terminator AND acts to induce suicide of
    viral polymerase
    True
  16. Which of the following is not a
    resistance mechanism for acyclovir
    A. Absence of viral thymidine kinase activity
    B. Reduced uptake of acyclovir
    C. Altered thymidine kinase substrate
    specificity
    D. Altered viral DNA polymerase
    B
  17. T/F Acyclovir has poor
    bioavailability, wide distribution, and irreversible renal dysfunction in 5% of
    patients.
    False (REVERSIBLE dysfunction)
  18. T/F: Acyclovir has affinity for
    human polymerase same as viral polymerase.
    False
  19. What is the prodrug form of acyclovir called?
    valacyclovir
  20. Cidofovir is a _____ nucleotide
    analog with inhibitory activity against many viruses.
    cytidine
  21. T/F: Cidofovir is phosphorylated
    by viral enzymes and to a lesser extent cellular enzymes.
    False– Cellular but not viral enzymes
  22. Cidofovir acts as competitive
    inhibitor to ___ while acyclovir inhibits ___
    dCTP, dGTP
  23. T/F: cidofovir has a long half life
    (87 hr) which allows for infrequent dosing
    True
  24. Viral polymerase is inhibited at ____ concentration
    than in mammalian cells
    lower
  25. _____ resistance crosses to
    cidofovir
    ganciclovir
  26. 90% of cidofovir is eliminated unchanged via…
    Glomerular filtration and tubular secretion
  27. What is the dose limiting toxicity
    for cidofovir?
    nephrotoxicity
  28. Cidofovir and concomitant administration of
    _____ reduces potential toxicities
    probenacid
  29. Cidofovir is indicated IV for
    _____ resistant HSV and ____ _____ in HIV infected patients.
    Acyclovir, CMV retinitis
  30. Penciclovir is an acyclic ______
    nucleoside analog
    guanine
  31. Penciclovir’s prodrug is …
    famciclovir
  32. Penciclovir has ____ potency and spectrum of
    activity as acyclovir
    similar
  33. Penciclovir contains a ____, so it
    is NOT a chain terminator
    3'-OH
  34. If penciclovir is 1/100 as potent
    as acyclovir what makes it so effective?
    Present in higher concentrations and over prolonged time
  35. ______ resistant HSV is
    cross-resistant to penciclovir
    Acyclovir
  36. This antiviral is used for chronic HBV hepatitis
    Famciclovir (penciclovir)
  37. This drug is a long-chain alcohol
    cream for orolabial herpes
    docosanol
  38. What is the MOA of docosanol?

    Inhibits viral uptake into thecell, blocks membrane fusion
  39. This antiviral is the first FDA approved
    antisense therapy
    fomivirsen
  40. What is fomivirsen’s MOA?

    Binds mRNA of major immediate-early transcriptional region of CMV, inhibiting replication
  41. ROA for fomivirsen for CMV
    retinitis
    Intravitreal injection

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