EXAM #4: ANTIVIRAL DRUGS Flashcards
What type of genome do the Herpesviruses contain?
dsDNA
What is being targeted in some way by all the drugs that treat Herpesviruses?
viral DNA polymerase
What stage of disease caused by the Herpesviruses is targeted by antiviral drugs?
Lytic stage i.e. productive phase of infection ONLY
What type of drug is Acyclovir?
Nucleoside analog
What is the MOA of Acyclovir?
1) Competitive inhibitor of viral DNA polymerase
2) Causes chain termination via incorportation into the viral genome
What is required for the activation of Acyclovir?
Phosphorylation by viral thymidine kinase
How causes resistance with Acyclovir?
Mutation of thymidine kinase
What are the clinical indications for ORAL Acyclovir?
1) Genital herpes (HSV-2)
2) Varicella zoster (VZV)
What are the clinical indications for IV Acyclovir?
1) Severe/ disseminated disease
2) Neonate infections
3) HSV encephalitis
4) VZV in immunocompromised patients
What major toxicity is associated with Acyclovir?
Nephrotoxicity
This is combated partly by proper hydration prior to administration
What is Valacyclovir?
Acyclovir prodrug with a Valine moiety
What is the utility of Valacyclovir?
Increased oral bioavilibility compared to Acyclovir
What are the clinical indications for Valacyclovir?
1) Genital herpes (HSV-2)
2) Varicella
3) Oral herpes (HSV-1)
What is unique about Foscarnet compared to Acyclovir?
Does NOT require phosphorylation by Thymidine Kinase
What are the indications for Foscarnet?
1) HSV and VZV infections that are RESISTANT to Acyclovir
2) CMV Retinitis
3) CMV Colitis
4) CMV Esophagitis
*Note that it is ONLY given IV
What is the major toxicity associated with Foscarnet?
1) Renal impairment/ nephrotoxicity
2) Changes in blood chemistry
What type of drug is Ganciclovir?
Acyclic guanosine analog
What is the MOA of Ganciclovir?
1) Phosphorylation by CMV viral kinase
2) Competitive inhibition of viral DNA polymerase
3) Chain termination upon incorportion
How does Ganciclovir compare to Acyclovir?
B/c it is phosphorylated by a CMV enzyme, it is much more effective in treating CMV infections
What is the mechanism of Ganciclovir resistance?
Mutation of the CMV viral kinase (UL97)
What are the clinical indications for Ganciclovir?
1) CMV-anything
2) Prevention of CMV disease in transplant recipients
How is Ganciclovir administered for CMV retinitis?
Intraocular
What are the major adverse effects associated with Ganciclovir?
1) Myelosuppression
2) CNS toxicity
3) Injection site reaction to IV
What is Valganciclovir?
Prodrug of Ganciclovir
*Higher oral bioavalibility
What are the clinical indications for Valganciclovir?
1) CMV Retinitis
2) Prophylaxis in transplant recipients
What type of drug is Trifluridine?
Fluorinated pyrimidine nucleoside
What is the MOA of Trifluridine?
1) Phosphorylation by cellular enzymes
2) Competitive inhibition of thymidine incorporation into DNA
What are the clinical indications for Trifluridine?
HSV-1 and HSV-2 induced:
- Keratoconjunctitivitis
- Keratitis
What type of virus is the Influenza virus?
Segmented ssRNA