Fitz, HSV, H/VZV, CMV Flashcards Preview

MED234 Respiratory > Fitz, HSV, H/VZV, CMV > Flashcards

Flashcards in Fitz, HSV, H/VZV, CMV Deck (25):
1

Name the four Acyclic NucleoSides.
All of these nucleoSides are analogs of what purine nucleoTides?

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

Analogs of Guanosine analogs

2

Name the one non-nucleoside

Foscarnet

3

HSV and VZV, think what two drugs.
What admin route?

Acyclovir and Gancyclovir
Both IV

4

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

Foscarnet

5

CMV, think what three drugs (and administration route)

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

-Foscarnet, IV/topical, pyrophosphate

6

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

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.

7

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

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

8

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

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

9

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

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

10

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

INHIBITION of viral DNA polymerase

11

Mechanisms of resistance to ACV and GCV.
(selectivity for infected cells)

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

12

Bioavailability of nucleoside esthers

High ORAL bioavailablity

13

Valacyclovir ---> Acyclovir
1. Admin route
2. Distribution to CNS?
3. Elimination route

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

14

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

HSV
Tx with acyclovir

15

Can acyclovir be given to pregnant women?

Yes

16

Toxicity of acyclovir (2).

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

17

How can acute renal failure be avoided in acyclovir administration?

Hydrate and slow influsion

18

Valganciclovir ---> Ganciclovir
1. Admin route
2. Distribution to CNS?
3. Elimination route

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

19

Two reasons/indications for usage of Gangciclovir

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

20

Toxicity of Ganciclovir/Valganciclovir (4)

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

21

How does Foscarnet differ from antiviral nucleosides?

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

22

MOA of Foscarnet

Inhibits DNA polymerase in HSV, VZV, CMV

23

Foscarnet has two main clinical uses.

1. CMV RETINITIS
2. Acyclovir-resistant HSV, VZV

24

CMV retintis, think what two drugs to treat?

ganciclovir and foscarnet

25

Three adverse affects of foscarnet

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