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41 Cards in this Set
- Front
- Back
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What are the antiviral nucleoside analogs?
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Ganciclovir
Acyclovir Penciclovir Cidofovir |
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What is the basis of selectivity for the antiviral nucleosie analogs?
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Viral polymerases will accept these compounds as substrates; ours won't
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What nucleotide are ganciclovir and acyclovir imitating?
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Deoxyguanosine
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What is a requirement for activity of the antiviral nucleosie analogs?
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Phosphorylation
Incorporation into a viral nucleic acid |
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What is the mechanism of the antiviral nucleoside analogs?
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Incorporation into a viral nucleic acid, halting viral proliferation by messing with the DNA
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What step of the activation of acyclovir is performed in herpes?
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The first phosphorylation step:
Acyclovir --> Acyclovir-MP |
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What are the mechanisms of viral specificity in acyclovir?
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The first phosphorylation step
Incorporation into the viral DNA |
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What antiviral nucleosiDe analogs is also activated by a cellular kinase?
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Cidofovir
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Which antiviral nucleosie analogs is incorporated into host cell nucleic acids?
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Ganciclovir - IT HAS MORE ADVERSE EFFECTS THAN ACYCLOVIR; THIS MAKES SENSE!
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Which of the antiviral nucleoside analogs aren't as safe as the others? Why?
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Ganciclovir (incorporated into host cell nucleic acids)
Cidofovir (activated by host cell kinases) |
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What is the mechanism of resistance to antiviral nucleoside analogs? Which is the most common
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Mutation in the kinases that activate the drugs (most common)
Mutation in the viral DNA polymerase |
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What is the absorption of acyclovir?
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Poor! 10-20%
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What is done to acyclovir to make it more orally bioavailable?
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Addition of a valine --> valacyclovir
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What is the absorption of valacyclovir?
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Orally bioavailable 50%
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What is the distribution of acyclovir and valacyclovir?
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All tissues
Goes to the CSF well! |
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What is the metabolism and half-life of acyclovir and valacyclovir?
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Little metabolism
t1/2 = 2.5 hr. |
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What is the excretion of acyclovir and valacyclovir?
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Renally
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What are the averse effects of acyclovir?
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VERY SAFE!
GI upsed Hedache Renal toxicity (ppts in renal tubules; if already have renal problems this can exacerbate them) |
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What are the clinical uses of acyclovir?
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Herpes simplex virus: herpes encephalitis, genital herpes, mucocutaneous herpes
Varicella zoster virus (shortening duration) |
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What is the absorption of ganciclovir, valganciclovir?
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Oral bioavailability:
Ganciclovir <10% Valganciclovir = 60% |
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What is the distribution of ganciclovir and valganciclovir?
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Well distributed
GOES TO THE CSF! |
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What is the metabolism and half life of ganciclovir and valganciclovir?
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Little metabolism
T1/2 = 2-4 hrs |
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What is the excretion of ganciclovir and valganciclovir?
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Renally
It's eliminated unchanged |
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What are the adverse effects of ganciclovir?
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MUCH MORE SIGNIFICANT THAN ACYCLOVIR!
Bone marrow toxicity: neutropenia, thrombocytopenia CNS effects: dizziness, confusion, headache |
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What are the uses of ganciclovir?
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Prevention and treatment of CMV infections
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What viral infection shouldn't you treat with acyclovir? Why?
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CMV infections
CMV doesn't activate acyclovir via phosphorylation |
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How is penciclovir typically administered?
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As a topical cream for herpes leabialis
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What is the relation of penciclovir and famiciclovir to ganciclovir?
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Penciclovir and famiciclovir are analogs of ganciclovir
They've got similar mechanisms of action, resistance as ganciclovir |
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What is the relationship of famiciclovir to penciclovir?
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Famiciclovir is the prodrug of penciclovir for oral administration
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What nucleoside is cidofovir similar to?
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Deoxycytadine
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What is unique about the activation of cidofovir?
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It doesn't need to have the initial phosphorylation performed
However, it still needs to have the other phosphorylation steps performed |
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What is the mechanism of selectivity for cidofovir?
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Specific to the viral DNA polymerase
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What is the half-life of cidofovir?
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LOOOONNNNGGGGG!
You can dose this once a week |
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What are the clinical uses of cidofovir?
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CMV infection
Acyclovir-resistant HSV |
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What are the adverse effects of cidofovir? How are these prevented?
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Nephrotoxicity
Probenecid is given to decrease this |
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How is cidofovir administered?
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IV
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What is the structure of foscarnet?
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Just like a phosphate, with a carboxylic acid added
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What is unique about foscarnet?
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It doesn't require activation
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What is the mechanism of action for foscarnet?
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Interfering with DNA synthesis in viruses at the phosphate binding site of the polymerase
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What are the clinical uses of foscarnet?
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CMV
Acyclovir-resistant herpes |
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In CMV, which antiviral drug is least likely to be ineffective due to mutations?
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Foscarnet
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