(7) Antimicrobials: Antivrials Other (8.1-8.2) Flashcards
MOA: Acyclovir
Guanosine analog
(⇒ Inhibition of viral DNA synthesis)
What enzymes activate Acyclovir?
(1) First Phosphorylation: Viral Thymidine-kinase
(2) Second & Third: Cellular kinase
What is the rate-limiting enzyme in the activation of Acyclovir?
Viral Thymidine-kinase
(Note: This specific herpesvirus enzyme ∴ Acyclovir is ineffective against CMV/EBV)
Resistance: Acyclovir
Absence of Viral Thymidine-kinase
(∴ Acyclovir does not undergo the necessary initial phosphorylation to become activated)
Name 2 drugs with the following characteristics:
(1) Do not require phosphorylation to become active
(2) Spectrum of activity similar to Acyclovir/Ganciclovir
(1) Cidofovir
(2) Foscarnet
MOA: Foscarnet
DIRECTLY inhibits Viral DNA Polymerase
(Cidofovir has the same MOA)
What is the preferred antiviral to use as a daily HSV suppressive therapy
Valacyclovir
(Val-acyclovir is an acyclovir prodrug with good oral bioavailability)
ROA: Valacyclovir
Oral
ROA: Acyclovir
IV
Which antiviral is used to treat HSV encephalitis?
Acyclovir
(Acyclovir is likely preferred over Valacyclovir in serious situations due to IV administration)
What are the 2 preferred antivirals to treat shingles?
(1) Famcyclovir
(2) Valacyclovir
* (Acyclovir is adequately effective, it is a pharmacokinetics issue)*
In order to be maximally effective against shingles, within what timeframe should antivirals be given?
Within 3 days of onset of symptoms
Name 2 populations where Acyclovir is used for HSV prophylaxis
(1) Immunocompromised
(2) Pregnant woman with active HSV
* (Immunocompromised such as organ transplant recipient or HIV patient)*
Adverse Effects (2) : Acyclovir
(1) Interstitial nephritis/Crystalline nephropathy
(2) CNS effects
How does a cytomegalovirus infection usually present in an HIV patient?
Retinitis ⇒ Hemorrhages and infiltrates
CD4: CMV
CD4 < 50
Why does Ganciclovir preferentially target CMV infected cells?
Activated by Viral Kinase UL97
What enzyme activates Ganciclovir?
Viral Kinase UL97
(For first phosphorylation, then cellular kinase for second and third)
MOA: Ganciclovir
Guanosine nucleoside analog
(⇒ Inhibition of Viral DNA polymerase)
What is an orally administered version of Ganciclovir?
Valganciclovir
(Val- prefix = prodrug)
Who is Ganciclovir indicated for?
High-risk transplant patients
Adverse Effect: Ganciclovir
Myelosuppression
An HIV patient is on Zidovudine as an anti-retroviral and Ganciclovir as prophylaxis for CMV. What lab values must you constantly follow?
WBC/RBC counts
What viruses is Foscarnet active against?
(1) HSV
(2) VZV
(3) CMV
What organ does Cidofovir commonly damage?
Kidney
(Foscarnet also commonly damages the kidney)
What electrolyte abnormalities are common with Foscarnet?
(1) ↓ Ca2+
(2) ↓ Mg2+
(3) ↓ K+
What antiviral is always administered with Probenecid?
Cidofovir
How does Probenecid protect the kidney from Cidofovir?
Inhibits tubular secretion
(∴ Reduced intra-lumenal Cidofovir concentration ⇒ Reduced toxicity)
