Fitz, HSV, H/VZV, CMV

Question 1

Name the four Acyclic NucleoSides.

All of these nucleoSides are analogs of what purine nucleoTides?

Answer 1

Valacyclovir (prodrug) —(De-acylation, esterases)—> Acyclovir
Valganciclovir (esther prodrug) —(De-acylation, esterases)—> Gancyclovir

Analogs of Guanosine analogs

Question 2

Name the one non-nucleoside

Answer 2

Foscarnet

Question 3

HSV and VZV, think what two drugs.

What admin route?

Answer 3

Acyclovir and Gancyclovir

Both IV

Question 4

If HSV/VZV are acyclovir resistant, use what drug.

Answer 4

Foscarnet

Question 5

CMV, think what three drugs (and administration route)

Answer 5

• Ganciclovir, IV, nucleoSide
• Valganciclovir, PO, ESTER of nucleoSide

-Foscarnet, IV/topical, pyrophosphate

Question 6

How do nucleoside drugs inhibit virus replication in infected cells (2 ways)?

Answer 6

1. Triphosphate form of the drug inhibits viral DNA polymerase
2. NTTPs terminate viral DNA bc they lack 3’-OH and “terminate” additional nucleotide addition to DNA chain.

Question 7

Do any nucleoside drugs act selectively on virus-infected cells, while sparing non-infected cells?

Answer 7

Yes - the nucleoSides must be transformed into their nucleoTide triphosphate form by VIRAL KINASES to be active.

Question 8

Do viral or host kinases (and which ones) cause mono-phosphorylation?

Answer 8

Viral Kinases cause mono-phosphorylation?
HSV/VZV: Acyclovir —(Thymidine Kinase)—> ACV-P
CMV: Ganciclovir —(UL97 Kinase)—> CMV-P

Question 9

Do viral or host kinases convert mono-phosphate to di- and tri- phosphates?

Answer 9

Host cell kinases
ACV-P —> ACV-PP —> ACV-PPP
GCV-P —> GCV-PP —>GCV-PPP

Question 10

After formation of ACV-PPP and GCV-PPP, what then happens?

Answer 10

INHIBITION of viral DNA polymerase

Question 11

Mechanisms of resistance to ACV and GCV.

selectivity for infected cells

Answer 11

1. Neutralize viral-dependent drug activation processes - kinase MUTATION
2. Neutralize drug targets.

Question 12

Bioavailability of nucleoside esthers

Answer 12

High ORAL bioavailablity

Question 13

Valacyclovir —> Acyclovir

1. Admin route
2. Distribution to CNS?
3. Elimination route

Answer 13

1. Oral —> IV
2. Distribution to CNS - YES
3. Elimination route - renal

Question 14

Encephalitis could be caused by what virus and tx with what drug?

Answer 14

HSV

Tx with acyclovir

Question 15

Can acyclovir be given to pregnant women?

Answer 15

Yes

Question 16

Toxicity of acyclovir (2).

Answer 16

1. Acute renal failure - with precipitation of ACV in renal tubules.
2. Neurologic toxicity - tremors, delerium, myoclonus, hallucinations

Question 17

How can acute renal failure be avoided in acyclovir administration?

Answer 17

Hydrate and slow influsion

Question 18

Valganciclovir —> Ganciclovir

1. Admin route
2. Distribution to CNS?
3. Elimination route

Answer 18

1. Oral —> IV
2. Distribution to CNS? YES
3. Renal elimination

Question 19

Two reasons/indications for usage of Gangciclovir

Answer 19

1. Treatment and suppression of CMV RETINITIS in immunocompromised
2. Prevention of CMV in transplant paitents

Question 20

Toxicity of Ganciclovir/Valganciclovir (4)

Answer 20

1. Bone marrow suppression
2. Hematologic toxicity
3. Renal toxicity - especially in pts taking nephrotoxic or immunosuppressive drugs (i.e. cyclosporine)
4. Pregnancy category C

Question 21

How does Foscarnet differ from antiviral nucleosides?

Answer 21

Does not require activation - independent of viral or cell kinases.

Question 22

MOA of Foscarnet

Answer 22

Inhibits DNA polymerase in HSV, VZV, CMV

Question 23

Foscarnet has two main clinical uses.

Answer 23

1. CMV RETINITIS

2. Acyclovir-resistant HSV, VZV

Question 24

CMV retintis, think what two drugs to treat?

Answer 24

ganciclovir and foscarnet

Question 25

Three adverse affects of foscarnet

Answer 25

1. Nephrotoxic
2. Accumulation in bone matrix
3. Hypocalcemia