(7) Antimicrobials: Antivrials Other (8.1-8.2)

Question 1

MOA: Acyclovir

Answer 1

Guanosine analog

(⇒ Inhibition of viral DNA synthesis)

Question 2

What enzymes activate Acyclovir?

Answer 2

(1) First Phosphorylation: Viral Thymidine-kinase
(2) Second & Third: Cellular kinase

Question 3

What is the rate-limiting enzyme in the activation of Acyclovir?

Answer 3

Viral Thymidine-kinase

(Note: This specific herpesvirus enzyme ∴ Acyclovir is ineffective against CMV/EBV)

Question 4

Resistance: Acyclovir

Answer 4

Absence of Viral Thymidine-kinase

(∴ Acyclovir does not undergo the necessary initial phosphorylation to become activated)

Question 5

Name 2 drugs with the following characteristics:

(1) Do not require phosphorylation to become active
(2) Spectrum of activity similar to Acyclovir/Ganciclovir

Answer 5

(1) Cidofovir
(2) Foscarnet

Question 6

MOA: Foscarnet

Answer 6

DIRECTLY inhibits Viral DNA Polymerase

(Cidofovir has the same MOA)

Question 7

What is the preferred antiviral to use as a daily HSV suppressive therapy

Answer 7

Valacyclovir

(Val-acyclovir is an acyclovir prodrug with good oral bioavailability)

Question 8

ROA: Valacyclovir

Answer 8

Oral

Question 9

ROA: Acyclovir

Answer 9

IV

Question 10

Which antiviral is used to treat HSV encephalitis?

Answer 10

Acyclovir

(Acyclovir is likely preferred over Valacyclovir in serious situations due to IV administration)

Question 11

What are the 2 preferred antivirals to treat shingles?

Answer 11

(1) Famcyclovir
(2) Valacyclovir
* (Acyclovir is adequately effective, it is a pharmacokinetics issue)*

Question 12

In order to be maximally effective against shingles, within what timeframe should antivirals be given?

Answer 12

Within 3 days of onset of symptoms

Question 13

Name 2 populations where Acyclovir is used for HSV prophylaxis

Answer 13

(1) Immunocompromised
(2) Pregnant woman with active HSV
* (Immunocompromised such as organ transplant recipient or HIV patient)*

Question 14

Adverse Effects (2) : Acyclovir

Answer 14

(1) Interstitial nephritis/Crystalline nephropathy
(2) CNS effects

Question 15

How does a cytomegalovirus infection usually present in an HIV patient?

Answer 15

Retinitis ⇒ Hemorrhages and infiltrates

Question 16

CD4: CMV

Answer 16

CD4 < 50

Question 17

Why does Ganciclovir preferentially target CMV infected cells?

Answer 17

Activated by Viral Kinase UL97

Question 18

What enzyme activates Ganciclovir?

Answer 18

Viral Kinase UL97

(For first phosphorylation, then cellular kinase for second and third)

Question 19

MOA: Ganciclovir

Answer 19

Guanosine nucleoside analog

(⇒ Inhibition of Viral DNA polymerase)

Question 20

What is an orally administered version of Ganciclovir?

Answer 20

Valganciclovir

(Val- prefix = prodrug)

Question 21

Who is Ganciclovir indicated for?

Answer 21

High-risk transplant patients

Question 22

Adverse Effect: Ganciclovir

Answer 22

Myelosuppression

Question 23

An HIV patient is on Zidovudine as an anti-retroviral and Ganciclovir as prophylaxis for CMV. What lab values must you constantly follow?

Answer 23

WBC/RBC counts

Question 24

What viruses is Foscarnet active against?

Answer 24

(1) HSV
(2) VZV
(3) CMV

Question 25

What organ does Cidofovir commonly damage?

Answer 25

Kidney

(Foscarnet also commonly damages the kidney)

Question 26

What electrolyte abnormalities are common with Foscarnet?

Answer 26

(1) ↓ Ca2+
(2) ↓ Mg2+
(3) ↓ K+

Question 27

What antiviral is always administered with Probenecid?

Answer 27

Cidofovir

Question 28

How does Probenecid protect the kidney from Cidofovir?

Answer 28

Inhibits tubular secretion

(∴ Reduced intra-lumenal Cidofovir concentration ⇒ Reduced toxicity)