Herpes Virus

Question 1

Antiviral chemotherapies for herpesvirus:

Answer 1

Nucleoside Analogs :
Acyclovir
Valacyclovir
Ganciclovir

Non-nucleoside analogs:
Foscarnet

Question 2

Therapeutic uses of Acyclovir:

Answer 2

Routes:
Topical, oral, IV

Antiviral spectrum:
HSV&raquo_space;VZV&raquo_space;»CMV (Not used b/c high dose is needed)

Question 3

Pharmacokinetics of acyclovir:

Answer 3

• widely distributed in the body including CSF
• metabolized by the liver and eliminated by kidney
• low oral bioavailability (valacyclovir is an L-Valyrian ester prodrug 5x more bioavailability > rapidly converted to acyclovir)

Question 4

AEs of acyclovir:

Answer 4

1) reversable renal dysfunction (acyclovir-induced crystalline nephropathy)
2) Neurotoxicity (tremor & seizur)

Question 5

M.O.A of acyclovir:

Answer 5

It’s a cyclic guanine nucleoside prodrug but lack a 3’OH group

1) converted by viral thymidine kinase to acyclovir-GMP
2) host cell TK converts acyclovir-GMP to Acyclovir-GDP & acyclovir-GTP inside infected cell
3) Acyclovir-GTP inhibit replication of viral DNA by 2 ways:

• incorporated into viral DNA by viral polymerase & cause chain termination
• inhibit viral DNA polymerase

Question 6

Resistance to acyclovir result from:

Answer 6

viral thymidine kinase (TK) deficiency

Question 7

Therapeutic uses of Ganciclovir:

Answer 7

❖ Routes: oral, IV and ocular insert
❖ Has activities against all herpesviruses
❖ Due to its toxicity, ganciclovir is restricted for:
- treatment of CMV retinitis In IC patients (ocular)
- prevention of CMV infection in transplant patients

Question 8

M.O.A of ganciclovir:

Answer 8

Similar to acyclovir

Question 9

AEs of ganciclovir:

Answer 9

❖ Myelosupression (dose-dependent)

Question 10

Therapeutic uses of Foscarnet (Non-Nucleoside Analogs:

Answer 10

❖ Has activity against all herpesviruses and HIV
❖ It is used mostly to treat:
- immunocompromised patients with CMV
- acyclovir-resistant viruses

Question 11

Pharmacokinetic of Foscarnet:

Answer 11

❖ It is not well absorbed by GIT, thus Usually foscarnet is given IV
❖ 80% eliminated unchanged by the kidneys

Question 12

M.O.A of foscarnet:

Answer 12

❖ It directly Inhibits herpesvirus DNA polymerase and HIV reverse transcriptase (already phosphorylated “active “ analog)

Question 13

AEs of foscarnet:

Answer 13

• Neohrotoxicity

- electrolyte disturbances