Antiviral Drugs

Question 1

Why can’t a lot of viral infections be cured?

Answer 1

DNA integration

Question 2

DOC for HSV and Herpes zoster

Answer 2

Acyclovir/Valacyclovir

Question 3

MOA acyclovir/valacyclovir

Answer 3

Guanosine analogue —> inhibits DNA synthesis by competing with dGTP

Requires phosphorylation and activation by VIRAL thymidine kinase

Question 4

Difference between acyclovir/valacyclovir

Answer 4

Val is a pro-drug that gets converted to acyclovir

Has a higher bioavailability (more effective, fewer doses needed compared to acyclovir)

Question 5

Acyclovir must be _______________ by ______________ in order to be able to incorporate itself into the viral DNA

Answer 5

Phosphorylated by herpes thymidine kinase.

Makes it very non toxic because becomes trapped by virus specific enzyme

Mechanism of resistance: mutation of thymidine kinase

Question 6

Adverse side effects of acyclovir

Answer 6

Very well tolerated due to concentration of drug within viral cells
(Nausea, vomiting, headache)
Nephrotoxicity with high IV does —> HYDRATION!
Safe in pregnancy

Question 7

Docosanol (Abreva)

Answer 7

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

Question 8

DOC for CMV

Answer 8

Ganciclovir/valganciclovir

Question 9

Blueberry babies

Answer 9

Results of congenital CMV infection —> severe mental/physical retardation

Occurs when mom has a primary infection while pregnant - always test pregnant women for CMV!

Question 10

Ganciclovir/Valganciclovir

Answer 10

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

Question 11

Ganciclovir toxicity

Answer 11

Myelosuppression

CNS penetration —> headaches

Question 12

Foscarnet (Foscavir)

Answer 12

Directly inhibits DNA/RNA polymerase, reverse transcriptase - doesn’t require phosphorylation for activity

Question 13

Therapeutic uses of foscarnet

Answer 13

IV Only
CMV encephalitis = foscarnet + ganciclovir
CMV retinitis (if ganciclovir resistant)
HSV if treating acyclovir/ganciclovir resistant HSV

Question 14

Foscarnet toxicity

Answer 14

Renal toxicity - make sure to hydrate aggressively when giving

Question 15

Cidofovir

Answer 15

Cytosine analogue - inhibits viral DNA polymerase
Phosphorylation is independent of viral enzymes

Used for ganciclovir resistant CMV and acyclovir-resistant HSV

Dose dependent nephrotoxicity

Question 16

MOA for Oseltamivir (Tamiflu) and Zanamivir (Relenza)

Answer 16

Neuraminidase inhibitors - block release of virus from the cells

Question 17

Therapeutic use for Tamiflu/Relenza

Answer 17

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

Question 18

DOC for RSV

Answer 18

Ribavirin (Virazole)

Question 19

Ribavirin MOA

Answer 19

Guanosine analogue, phosphorylated by HOST enzymes

Inhibits RNA polymerase

Question 20

Drug with highest incidence of occupational teratogenicity

Answer 20

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

Question 21

Ribavirin toxicity

Answer 21

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

Question 22

DOC for Hep B

Answer 22

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)

Question 23

DOC for Hep C

Answer 23

Harvoni (Sofosbuvir/Ledipasvir)
CURE but super duper expensive

Alternatives:
Epclusa
Zepatier

Question 24

MOA for Harvoni and Epclusa (

Answer 24

Inhibits RNA replication and protein assembly in Hep C

Very well tolerated —> Harvoni = CURE