Antiviral Drugs Flashcards
Why can’t a lot of viral infections be cured?
DNA integration
DOC for HSV and Herpes zoster
Acyclovir/Valacyclovir
MOA acyclovir/valacyclovir
Guanosine analogue —> inhibits DNA synthesis by competing with dGTP
Requires phosphorylation and activation by VIRAL thymidine kinase
Difference between acyclovir/valacyclovir
Val is a pro-drug that gets converted to acyclovir
Has a higher bioavailability (more effective, fewer doses needed compared to acyclovir)
Acyclovir must be _______________ by ______________ in order to be able to incorporate itself into the viral DNA
Phosphorylated by herpes thymidine kinase.
Makes it very non toxic because becomes trapped by virus specific enzyme
Mechanism of resistance: mutation of thymidine kinase
Adverse side effects of acyclovir
Very well tolerated due to concentration of drug within viral cells
(Nausea, vomiting, headache)
Nephrotoxicity with high IV does —> HYDRATION!
Safe in pregnancy
Docosanol (Abreva)
OTC for cold sores, herpes simplex
Not as good as acyclovir but can be used topically to treat
Inhibits viral fusion to host cell plasma membrane
DOC for CMV
Ganciclovir/valganciclovir
Blueberry babies
Results of congenital CMV infection —> severe mental/physical retardation
Occurs when mom has a primary infection while pregnant - always test pregnant women for CMV!
Ganciclovir/Valganciclovir
Guanosine analogue
Activated by viral kinases in cells infected with herpes/CMV
Activated drug inhibits DNA polymerase
Less selective than acyclovir AND more toxic
Can treat Co-infection of herpes/CMV BUT can’t use during pregnancy
Ganciclovir toxicity
Myelosuppression
CNS penetration —> headaches
Foscarnet (Foscavir)
Directly inhibits DNA/RNA polymerase, reverse transcriptase - doesn’t require phosphorylation for activity
Therapeutic uses of foscarnet
IV Only
CMV encephalitis = foscarnet + ganciclovir
CMV retinitis (if ganciclovir resistant)
HSV if treating acyclovir/ganciclovir resistant HSV
Foscarnet toxicity
Renal toxicity - make sure to hydrate aggressively when giving
Cidofovir
Cytosine analogue - inhibits viral DNA polymerase
Phosphorylation is independent of viral enzymes
Used for ganciclovir resistant CMV and acyclovir-resistant HSV
Dose dependent nephrotoxicity
MOA for Oseltamivir (Tamiflu) and Zanamivir (Relenza)
Neuraminidase inhibitors - block release of virus from the cells
Therapeutic use for Tamiflu/Relenza
Active against influenza A and B
• Must start within 48 hours - peak of viral replication
• Tamiflu can be used for bird flu too
Tamiflu is oral, approved for pt > 1 year
• Take with food
Relenza is nasal or oral inhaler, approved for pt >7
• Contraindicated for asthma, COPD
DOC for RSV
Ribavirin (Virazole)
Ribavirin MOA
Guanosine analogue, phosphorylated by HOST enzymes
Inhibits RNA polymerase
Drug with highest incidence of occupational teratogenicity
Ribavirin
Administered as an aerosol in a tent
Pregnant women and those planning to become pregnant SHOULD NOT be around patients receiving this treatment
No female provider of child-bearing age should be in the same room when being treated
Ribavirin toxicity
Oral —> hemolytic anemia
Aerosol —> respiratory depression, cardiac arrest, hypotension
IV —> psychiatric (taken off market)
Teratogenic category X drug - do not conceive for at least 6 months after exposure to the drug
DOC for Hep B
Tenofovir
• Adenosine analogue, inhibits HBV DNA polymerase, can also be used for HIV
• DOC b/c high response, low resistance
Entecavir
• Guanosine analogue, inhibits HBV DNA polymerase
• Rare hepatic encephalopathy
Lamivudine
• Cytosine analogue, inhibits HBV polymerase
• Resistance common after chronic use (>5 years)
DOC for Hep C
Harvoni (Sofosbuvir/Ledipasvir)
CURE but super duper expensive
Alternatives:
Epclusa
Zepatier
MOA for Harvoni and Epclusa (
Inhibits RNA replication and protein assembly in Hep C
Very well tolerated —> Harvoni = CURE
