Exam 4 - Stahelin Herpes viruses (study)

Question 1

acyclovir and valacyclovir
MOR:
SOA:

Answer 1

MOR: mutations in viral thymidine kinase AND/OR mutations in viral DNA polymerase
SOA: HSV-1, HSV-2, VZV

Question 2

penciclovir
MOR:
SOA:

Answer 2

MOR: Viral kinase mutations, cross-resistance between penciclovir and acyclovir occur
SOA: topical - recurrent herpes labialis (HSV-1)

Question 3

famciclovir
MOR:
SOA:

Answer 3

MOR: Viral kinase mutations, cross-resistance between penciclovir and acyclovir occur
SOA: oral - primary and recurrent genital herpes (HSV-2), acute herpes zoster

Question 4

ganciclovir and valganciclovir
MOR:
SOA:

Answer 4

MOR: mutations in CMV kinase (UL97) or CMV DNA polymerase (UL54)
SOA: CMV retinitis OR CMV prophylaxis (oral only)

Question 5

foscarnet
MOA:
MOR:
SOA:

Answer 5

MOA: inhibits viral DNA polymerase(main action), RNA polymerase and HIV RT
MOR: mutations in DNA polymerase or HIV RT
SOA: CMV retinitis, synergistic w/ ganciclovir

Question 6

cidofovir
MOR:
SOA:

Answer 6

MOR: N/A
SOA: CMV, HSV-1, HSV-2, VZV, adenovirus, poxvirus, polyomarvirus, and human papillomavirus (only used for CMV retinitis tho)

Question 7

letermovir
MOA:
MOR:
SOA:

Answer 7

MOA: highly specific for CMV - binds to pUL56 on terminase complex
MOR: N/A
SOA: prophylaxis of CMV infection and disease in adult HSCT patients who have CMV

Question 8

which drugs are chain terminators?

Answer 8

acyclovir/valacyclovir
pencicilovir/famciclovir (short chain)
ganciclovir/valganciclovir (short chain)
cidofovir

Question 9

which drugs incorporate into DNA?

Answer 9

acyclovir/valacyclovir
peniciclovir/famciclovir
ganciclovir/valganciclovir
cidofovir

Question 10

which of the drugs above are prodrugs?

Answer 10

valacylcovir
valganciclovir
famciclovir

Question 11

which drugs are cross-resistant?

Answer 11

-viral kinase mutants against penciclovir confer resistance to acyclovir
-mutations in DNA polymerase against ganciclovir confer resistance to cidofovir or foscarnet
-CMV isolates resistant to foscarnet are cross resistant to ganciclovir

Question 12

Describe the binding site of foscarnet on DNA polymerase.

Answer 12

blocks pyrophosphate binding site of the viral DNA polymerase which inhibits cleavage of pyrophosphate from dNTPs; traps DNA polymerase in closed formation

Question 13

Explain the resistance/cross-resistance between cidofovir, foscarnet, and ganciclovir.

Answer 13

No cross resistance between the 3 if it is a kinase mutation.
DNA polymerase mutations, however, may confer resistance.

Question 14

How is cidofovir metabolized to its active species?

Answer 14

by intracellular enzymes

Question 15

Explain why valacyclovir and valganciclovir have greater bioavailability than acyclovir and ganciclovir.

Answer 15

valyl ester increases absorption and bioavailability

Question 16

differences between acyclovir and valacyclovir

Answer 16

acyclovir bioavailability: 15-30%
valacyclovir bioavailability: 48-54%

Question 17

differences between ganciclovir and valganciclovir

Answer 17

ganciclovir bioavailability: 6-9%
valganciclovir: bioavailability: 60%