Pharmacology Exam 1

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Author:
Rx2013
ID:
61286
Filename:
Pharmacology Exam 1
Updated:
2011-01-22 13:03:20
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Anti Viral Agents
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Anti-Viral Agents
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  1. Viruses consist of particles containing
    • nucleic acid
    • either RNA or DNA
    • single or double stranded
  2. Enveloped viruses
    • herpes simplex
    • varicella
    • HIV
  3. non-enveloped viruses
    adenovirus
  4. Envelope protein antibodies found in HIV patients
    GP120
  5. Latency stage
    cannot be targeted by current therapeutics
  6. Targets of antiviral therapy
    • attachment
    • entry
    • uncoating
    • puring and pyrimidine analogs
    • reverse transcriptase inhibitors
    • protease inhibitors
    • viral release
  7. Antiviral agents against herpes simplex & varicella zoster
    • acyclovir
    • valacyclovir
    • famciclovir
  8. Herpes simplex latency is controlled by
    the immune system
  9. Acyclovir is active against
    • HSV-1, 2 (most effective)
    • VZV
    • CMV
    • EBV
  10. Acyclovir is a _____ analog
    acyclic quanine nucleoside
  11. Acyclovir has ____ oral bioavailability and a half life of ____.
    • low
    • 2-3 hr
  12. Acyclovir works by
    • preventing 5'=>3' synthesis
    • results in chain termination
  13. Mechanism of action for Acyclovir
    phosphorylation of viral thymidine kinase blocks 5'-3' elongation
  14. Side effects of acyclovir
    • pain at injection site
    • crystalline nephropathy
  15. Valacyclovir
    • prodrug converted to acyclovir
    • increased stability & bioavailability (54%)
  16. Famciclovir
    • Prodrug converted to penciclovir
    • guanosine analogue
  17. Famciclovir is active against
    • HSV 1&2
    • VZV
    • EBV
    • HBV
  18. Famciclovir is activated by
    viral thymadine kinase
  19. Mechanism of action for famciclovir
    • inhibits DNA polymerase directly
    • no effect on chain elongation/termination
  20. Famciclovir compared to Acyclovir
    • lower affinity for viral TK than acyclovir
    • achieves higher intracelluar concentrations than acyclovir
  21. Penciclovir use
    available for topical application against herpes labialis
  22. Cytomegalo virus
    • Large DNA virus
    • Herpes virus
    • associated with salivary glands
    • problem in immunocomprimised pt
  23. Cytomegalovirus is considered to be
    an AIDS defining infection
  24. Antiviral agents used to compbat cytomegalovirus
    • ganciclovir
    • valganciclovir
    • foscarnet
    • cidofovir
  25. Ganciclovir
    • guanosine analog
    • Prodrug
    • short half life (2-4hrs)
  26. Mechanism of action for ganciclovir
    prevents chain elongation
  27. Resistance to ganciclovir
    • mutations in the drug target phosphotransferase
    • cross resistance with strains resistant to acyclovir
  28. Uses for ganciclovir
    CMV retinitis
  29. Side effects of ganciclovir
    • bone marrow suppression
    • lack of neutrophils (bad for HIV pt)
  30. Valganciclovir
    • ganciclovir prodrug
    • same MoA and effects as ganciclovir
    • activated by intestines and liver
  31. Foscarnet
    pyrophosphate analog
  32. Foscarnet is active against
    • HSV
    • VZV
    • CMV
    • EBV
    • HHV-6
    • KSHV
    • HIV-1
  33. Foscarnet availability
    • IV only due to poor absorption
    • 30% deposit into bone making half life months
  34. Foscarnet compared to ganciclovir for CMV
    same efficacy
  35. Foscarnet side effects
    • nephrotoxicity
    • hyperphosphatemia
    • hypomagnesemia
    • n/v
    • CNS toxicity
  36. Cidofovir mechanism of action
    binds viral DNA polymerase blocking DNA synthesis
  37. Cidofovir uses
    • CMV retinitis
    • acyclovir resistant herpes
    • papilomavirus
    • poxvirus
    • adenovirus
    • polumavirus
  38. Cidofovir side effects
    • nephrotoxicity
    • uveitis
    • ocular hypotony
    • neutropenia
  39. Ways to reduce nephrotoxicity of Cidofovir
    administer probenecid 3h before, 2h and 8hr after
  40. Hep A
    • no long term liver damage
    • low mortality
    • developing countries
  41. Hep B
    • hepadenavirus
    • DNA polymerase activity
    • Reverse transcriptase activity
  42. Hep C
    single stranded RNA virus
  43. Commonalities between Hep B, Hep C and HIV
    • Reverse transcriptase activity (B)
    • single stranded RNA virus (C)
  44. Hepatitis compared to Herpes viruses
    not genetically related
  45. Drugs for Hep B
    • Lamivudine
    • Adefovir
    • Entecavir
    • Interferon alpha 2B
  46. Lamivudine
    • Hep B
    • nucleoside analog (NRTI)
    • once daily
  47. Adefovir
    • Hep B
    • NRTI
    • not for HIV
    • nephrotoxic at high doses
  48. Entevavir
    • Guanosine nucleoside analog
    • once daily
    • Hep B
  49. Interferon alpha 2B
    • Hep B & C
    • once daily or 3 times weekly injection
  50. Drugs for Hep C
    • Ribavirin
    • Interferon alpha 2A and B
  51. Ribavirin
    • Hep C
    • inhibits capping of viral mRNA
    • teratogenic
  52. Influenza A
    • part of its life cycle in another host and can mutate differently than B
    • more recombinant events with A
  53. Influenza B
    more genetic drift
  54. Zanamivir
    • prodrug activated by esterase in GI and liver
    • inhibitor of influenza A & B neuraminidases
    • low oral bioavailabilty
  55. Zanamivir mechanism of action
    prevents release of virus from infected cells
  56. Osteltamivir
    • prodrug activated by esterase in GI and liver
    • inhibitor of neuraminidase
    • prevents viral release
    • high oral bioavailability
  57. Amantadine & Rimantadine
    • inhibit uncoating of viral RNA
    • well absorbed
    • Rimantidine 4-10x stronger than amantadine
    • influenza A
    • may be used with zanamivir and oseltamivir

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