Antivirals (non HIV/Hep)

Question 1

Herpes simplex virus (HSV) (profile)

Answer 1

2 most common types:
1st is oral
2nd is genital
man is only natural host

Question 2

Herpes simplex virus (HSV) that is fatal?

Answer 2

Neonatal HSV (transmission from mother to child)
rare but commonly FATAL to the child (25% of time)

Question 3

Acyclovir (MOA)

Answer 3

irreversible binding to elongating viral DNA, preventing republication from occurring
unique analog b/c it is IRREVERSIBLE

Question 4

what must nucleoside anti-viral drugs be transformed into for activity?

Answer 4

Nucleotide triphosphates

3 P groups

Question 5

Virus Kinases cause what kind of phosphorylation?

Answer 5

MONO-phosphorylation

Question 6

Virus Kinases (profile)

Answer 6

viruses have an enzyme that activates the antiviral drug, by adding a P group (the host cells add the other 2 P groups)
this means that the drug will not become active in cells that are not infected

Question 7

which virus uses Thymidine kinase?

Answer 7

Herpes simplex virus (HSV)
Varicella Zoster (VZV)

Question 8

which virus uses UL97 kinase?

Answer 8

Cytomegalovirus (CMV) only

Question 9

Virus to Drug?
HSV (herpes)
VZV (varicella)
CMV

Answer 9

HSV = ACV
VZV = PCV
CMV = GCV

Question 10

Who adds the other 2 P groups to antiviral drug?

Answer 10

Host cells (Cell kinases)

Question 11

Antiviral agents (non-retrovirals) (MOA)

Answer 11

inhibit viral DNA polymerase

Question 12

which nucleoside is Acyclovir similar to?

Answer 12

Guanosine

only difference is that Acyclovir does not contain a hydroxyl (OH) group

Question 13

Acyclovir (profile)

Answer 13

close to perfect antiviral drug
highly effective, highly selective against HSV
prodrug (means it needs to be activated)
activation requires 3 P groups

Question 14

Nucleoside Esters are prodrugs with ____ oral bioavilability

Answer 14

Higher

Question 15

Valacyclovir with De-acylation is ____?

Answer 15

Acyclovir

Question 16

Famciclovir with De-acetylation is ____ ?

Answer 16

Penciclovir

Question 17

Penciclovir vs Acyclovir

Answer 17

PCV is less active than ACV but has a longer half life (less frequency of administration required)

Question 18

Acyclovir (Adverse effects)

Answer 18

Well tolerated by most
Pregnancy cat B
if patient is dehydrated, crystal formation can occur (acute renal failure)

Question 19

Ganciclovir (profile)

Answer 19

active against CMV

CMV typically just develops in imunosupressed patients (cancer or transplants)

Question 20

Ganciclovir (Adverse effects)

Answer 20

associated with bone marrow suppression
monitor for hematologic and renal toxicity (especially with patients taking cyclosporine)
Pregnancy cat C

Question 21

how is Cidofovir activated?

Answer 21

host cell kinases convert to nucleotide triphosphate

no viral mediated phosphorylation

Question 22

Cidofovir (MOA)

Answer 22

inhibits viral DNA polymerase
used for ophthalmic infections in immunocompromised patients
used for CMV

Question 23

Cidofovir (adverse effects)

Answer 23

Systemic toxicity

Nephrotoxicity (do not use with NSAIDS)

Question 24

how do you lessen nephrotoxicity caused by Cidofovir?

Answer 24

administer with probenecid (blocks tubular secretions)

Question 25

Foscarnet (profile)

Answer 25

short half life (requires frequent administration)
cleared by glomerular filtration (nephrotoxic)
might want to use a catheter with this drug since it can make urination painful

Question 26

Foscarnet (adverse effects)

Answer 26

Accumulates in bone matrix
chelates Ca2+, Mg2+ (hypocalcemia)
electrolyte imbalances (seizures)

Question 27

Foscarnet (MOA)

Answer 27

no activation required (activity is independent of host and viral kinases)

Question 28

Foscarnet (indication)

Answer 28

1. used for CMV retinitis (immunocompromised patients)

2. Acyclovir-resistant HSV and VZV infections