Antiviral Drugs

Question 1

Influenza

Answer 1

Zanamivir, Oseltamivir (Tamiflu)

Question 2

What do Zanamivir and Oseltamivir (Tamiflu) inhibit?

Answer 2

Neuraminidase (unique to influenza virus)
Enzyme that cleaves sialic acid from glycoproteins
Required step in exit from infected cells

Question 3

Zanamivir and Oseltamivir (Tamiflu) are only effective if

Answer 3

Administered w/n 48 hours of onset

Question 4

Ribavirin is an analog of

Answer 4

Guanosine

Base attached to ribose has been changed

Question 5

Ribavirin inhibits

Answer 5

RNA Polymerase

Question 6

Ribavirin is triphosphorylated by

Answer 6

Cellular kinase enzymes

Question 7

What enzyme (besides RNA Polymerase) does Ribavirin inhibit?

Answer 7

`IMP dehydrogenase

Question 8

Ribavirin is an analog of guanosine and what else?

Answer 8

IMP: Biochemical intermediate that gets converted into guanosine

Question 9

Ribavirin MOA

Answer 9

Mimics IMP. Once bound to IMP dehydrogenase, guanosine nucleotides essential for viral replication can no longer be synthesized.

Question 10

Ribavirin uses

Answer 10

RSV
Hep C (with interferon)

Question 11

Ribavirin S/E

Answer 11

Hemolytic Anemia

Drug accumulates in RBCs and phosphorylates, contributing to ATP deficiency

Question 12

Which antiviral drug is highly teratogenic?

Answer 12

Ribavirin

Question 13

Acyclovir inhibits

Answer 13

herpes virus DNA polymerase

Question 14

Acyclovir mimics what to terminate chain growth?

Answer 14

Guanosine

Acyclovir is missing a ribose sugar

Question 15

What allows Acyclovir to target only infected cells?

Answer 15

Phosphorylated by herpes virus thymidine kinase

Becomes acyclovir monophosphate, which becomes triphosphate due to cellular kinases

Question 16

Acyclovir phosphate is an analog of

Answer 16

deoxyguanosine triphosphate (dGTP)

Question 17

What is the difference between Acyclovir and Famciclovir?

Answer 17

Longer half-life so lower dose can be used

Question 18

What is a prodrug of Acyclovir?

Answer 18

Valacyclovir

Has greater bioavailability so lower dose can be used

Question 19

What is the risk of giving Acyclovir via IV?

Answer 19

Nephrotoxicity (crystallizes in urine)

Must give with IV fluids

Question 20

Acyclovir is effective for

Answer 20

HSV-1, HSV-2 and VSV

Question 21

Acyclovir is not effective for what herpes viruses?

Answer 21

CMV and EBV

Have different viral kinase

Question 22

Which drugs inhibits CMV DNA polymerase?

Answer 22

Ganciclovir, Foscarnet, Cidofovir

Question 23

Ganciclovir has a similar MOA to

Answer 23

Acyclovir (guanosine analog)

Question 24

How does Ganciclovir become ganciclovir 5’-monophosphate?

Answer 24

IC conversion by CMV viral kinase

Question 25

Ganciclovir monophosphate becomes triphosphorylated by

Answer 25

cellular enzymes

Question 26

Major toxicity of Ganciclovir

Answer 26

Bone marrow suppression, especially leukopenia | Inhibits bone marrow DNA polymerase

Question 27

What is a prodrug of Ganciclovir?

Answer 27

Valganciclovir | Better bioavailability so can administer lower dose

Question 28

Ganciclovir is primarily administered via

Answer 28

IV due to poor bioavailability

Question 29

Valganciclovir is often preferred to Ganciclovir because

Answer 29

It can be administered orally (better bioavailability)

Question 30

Foscarnet

Answer 30

Pyrophosphate analog | Binds/inhibits DNA Polymerase

Question 31

Foscarnet is used when

Answer 31

Gancicovir fails | Acyclovir-resistant HSV and VSV

Question 32

Foscarnet S/E

Answer 32

Nephrotoxicity Calcium chelation (hypocalcemia) Induces renal wasting of Magnesium (hypomagnesaemia) Seizures (related to electrolytes)

Question 33

Cidofovir is an analog of

Answer 33

Cytidine | Cidofovir missing ribose sugar

Question 34

Cidofovir inhibits

Answer 34

DNA polymerase through cellular phosphorylation (no viral kinase needed)

Question 35

What is the main use of Cidofovir?

Answer 35

CMV retinitis

Question 36

What is the main toxicity of Cidofovir?

Answer 36

Renal failure | co-administer with saline and probenecid

Question 37

Interferons

Answer 37

Cytokines | Glycoproteins synthesized by infected cells and lymphocytes

Question 38

Interferon-alpha primes cells to fight against

Answer 38

Viruses

Question 39

Interferon-alpha used for

Answer 39

``` Hep B and C Kaposi sarcoma (HHV-8) ```