Antiviral Drugs

Question 1

Zanamivir, Oseltamivir

Answer 1

Influenza drugs

Question 2

Ribavirin

Answer 2

RSV, Hep C

Question 3

Acyclovir

Answer 3

Herpes viruses

Question 4

Ganciclovir, Foscarnet, Cidofivir

Answer 4

CMV drugs

Question 5

Interferon Tx

Answer 5

Viral infections

Question 6

Zanamivir/Osteltamivir (Tami-flu)

Answer 6

Neuraminidase inhibitors

Question 7

Neuraminidase is

Answer 7

enzyme that cleaves sialic acid from glycoproteins

-require for exit from cells

Question 8

Zanamivir/Osteltamivir (Tami-flu) must be administered w/n what time frame to be effective?

Answer 8

48 hours

Question 9

DNA/RNA polymerases work by

Answer 9

splits off two phosphates from nucleotriphosphates

uses remaining phosphate to form backbone

Question 10

What is a mechanism of resistance towards RNA/DNA polymerase inhibitors?

Answer 10

Viral kinase mutation

Question 11

Ribavirin mimics

Answer 11

Guanosine

-Has a different base attached

Question 12

Ribavirin is triphosphorylated by

Answer 12

Cellular kinases within infected cell

Question 13

Ribavirin inhibits

Answer 13

RNA polymerase

Question 14

What other enzyme besides RNA polymerase does Ribavirin inhibit?

Answer 14

Inhibits IMP dehydrogenase

• ribavirin mimics inosine monophosphate (biochemical intermediate that gets converted to guanosine nucleotides)
• decreases guanosine nucleotides available

Question 15

What are the two main uses of Ribavirin?

Answer 15

Severe RSV Tx

Combined with interferon to treat Hep C

Question 16

What is key S/E of Ribavirin?

Answer 16

Hemolytic Anemia

-Drug accumulates in RBCs and depletes phosphate pool, causing ATP deficiency

Question 17

Can you give Ribavirin to pregnant women?

Answer 17

No

Question 18

Acyclovir

Answer 18

Inhibits herpes DNA polymerase
Mimics guanosine
Acyclovir does not have a ribose sugar (O instead of OH)

Question 19

Acyclovir has a targeted effect (only works in effective cells) b/c

Answer 19

Acyclovir must be phosphorylated by herpes virus thymidine kinase
Cell enzymes converted acyclovir monophosphate into triphosphate.

Question 20

Acyclovir mimics what to inhibit viral DNA polymerase?

Answer 20

deoxyguanosine triphosphate (dGTP)

Question 21

Viruses develop resistance to Acyclovir by

Answer 21

decreasing viral thymidine kinase
altering viral thymidine kinase
altering viral DNA polymerase

Question 22

Famciclovir

Answer 22

Similar MOA to Acyclovir

Has a longer half-life so lower dose can be used

Question 23

Valacyclovir

Answer 23

Pro-drug converted to acyclovir

-Increased bioavailability so lower dose can be used

Question 24

Acyclovir administered by IV can cause

Answer 24

Nephrotoxicity

• Crystallizes in urine
• Administer with IV fluids

Question 25

HSV-1, HSV-2, and VZV tx

Answer 25

Acyclovir

Question 26

Acyclovir is not effective for CMV and EBV (also herpes viruses) because

Answer 26

They have a different viral kinase that cannot phosphorylate Acyclovir

Question 27

Tx for genital herpes, oral herpes, herpes encephalitis, herpes zoster

Answer 27

Acyclovir

Question 28

CMV infections are a big problem in

Answer 28

immunocompromised patients

Question 29

Ganciclovir, Foscarnet, Cidofivir

Answer 29

CMV drugs | -Inhibit CMV DNA Polymerase

Question 30

Ganciclovir

Answer 30

Similar MOA to Acyclovir | -mimics guanosine

Question 31

Major toxicity of Ganciclovir

Answer 31

Bone marrow suppression, especially leukopenia | Also inhibits bone marrow DNA polymerase

Question 32

Valganciclovir

Answer 32

Pro-drug that is converted to Ganciclovir | Better bioavailability

Question 33

Ganciclovir is administered by IV due to

Answer 33

Poor bioavailability

Question 34

If Ganciclovir must be administered orally for CMV infection,

Answer 34

Pt is given its pro-drug, Ganciclovir

Question 35

Foscarnet

Answer 35

Pyrophosphate Analog - Mimics phosphate group - DNA cannot cleave phosphate groups off nucleotide - Results in chain termination

Question 36

When is Foscarnet used?

Answer 36

CMV Tx when Ganciclovir fails | HSV/VSV Tx when there is resistance to Acyclovir

Question 37

Main limiting S/E of Foscarnet

Answer 37

nephrotoxicity

Question 38

Pts on Foscarnet must have electrolytes monitored b/c

Answer 38

Foscarnet chelates calcium - Causes hypocalcemia - Renal wasting of magnesium induced (hypomagnesaemia) - Resulting seizures

Question 39

Cidofovir

Answer 39

CMV drug Cytidine analog Viral DNA polymerase inhibitor

Question 40

Cidofovir undergoes phosphorylation by

Answer 40

Cellular kinase (not viral kinase)

Question 41

What is main use of Cidofovir?

Answer 41

CMV retinitis

Question 42

What is the main toxicity due to Cidofovir?

Answer 42

Renal Failure - Cidofovir is bound by anion transporter in proximal tubule, resulting in high concentrations in the renal cortex - Co-administer with saline to flush kidneys - Use probenecid (gout drug) to block Cidofovir accumulation in tubular cells

Question 43

Interferons

Answer 43

Used for anti-viral therapy Cytokines Glycoproteins synthesized by infected cells and lymphocytes Numerous immunomodulatory effects

Question 44

Interferon alpha primes cells to fight against

Answer 44

Hep B & C | HHV-8 (causes Kaposi's sarcoma)