Antiviral Agents

Question 1

What is the primary means to control viral spread?

Answer 1

Public health measures as well as prophylactic vaccines.

Question 2

How does influenza enter the host cell?

Answer 2

Hemagglutinin binds to the cell and the virus is endocytosis

Question 3

What happens when the endosome containing the influenza virus is acidified?

Answer 3

Two things: First there is a conformational change in hemagglutinin structure that mediates fusion between the influenza viral envelope and the endosomal membranes. Then, activation of viral M2 proton channel elicits the release of RNA genome.

Question 4

What two processes occur in order for the influenza to egress from the host cell?

Answer 4

1. Hemagglutinin interacts with cellular sialic acid moieties.
   2.Viral envelope-bound neuraminidases cleave the sequestered sialic acid moieties.
   Viral release

Question 5

What are the three inhibitors of viral neuraminidase?

Answer 5

1. Oseltamivir (Tamiflu)
2. Zanamivir (Relenza)
3. Peramivir (Rapivab)

Question 6

What does the inhibition of the enzyme neuraminidase lead to?

Answer 6

Virus aggregates at cell surface decreasing both intracellular viral translocation and viral budding

Question 7

Is resistance to inhibition of viral neuraminidase a particular problem?

Answer 7

Yes, but it is relatively rare 1-4%

Question 8

Describe the pharmacokinetics of Oselamivir.

Answer 8

Oseltamivir is an oral prodrug excreted renally

Question 9

Describe the pharmacokinetics of Zanamivir.

Answer 9

Zanamivir is inhaled and eliminated renally

Question 10

Describe the pharmacokinetics of Peramivir.

Answer 10

Peramivir is given as a single IV dose

Question 11

What type of influenza does neuramindase inhibitors, inhibit?

Answer 11

Both influenza A and B

Question 12

What are two drugs that inhibit the uncoating of influenza in the host cell?

Answer 12

Amantadine (Symmetrel) and Rimantadine (Flumadine)

Question 13

What is the target of amantadin and rimantadine?

Answer 13

Blocks the proton channel M2

Question 14

Describe the pharmacokinetics of amantadine.

Answer 14

Orally. Excreted renally

Question 15

Describe the pharmacokinetics of rimantadine.

Answer 15

Orally with hepatic elimination

Question 16

What group would you not prescribe amantadine or rimantadine.

Answer 16

Breast feeding mother. It is excreted through breast milk

Question 17

What type of influenza is used amantadine or rimantadine used for ?

Answer 17

Type A

Question 18

Name adverse reactions of amantadine and rimantadine.

Answer 18

Amantadine- insomnia, [] difficulties,

Rimantadine- poor CNS penetration. Not for use in pregnant women

Question 19

Acyclovir, Valacyclovir, Penciclovir, and Famciclovir are all examples of what?

Answer 19

Inhibitors of viral genome replication in the treatment of herpes infection.

Question 20

What enzyme converts nucleoside analogs to the active triphosphate form?

Answer 20

VIRAL thymidine kinase

Question 21

What drug competes with dGTP to terminate viral replication? Hint: It also irreversibly binds and inactivates viral DNA polymerase

Answer 21

Acyclovir-TP

Question 22

How do herpes viruses gain resistance to inhibitors of viral genome?

Answer 22

They reduce or loose expression of viral thymidine kinase

Question 23

What are the pharmacokinetics of viral inhibition of replication drugs?

Answer 23

Acyclovir- Poor oral, IV or topical
Valacyclovir- prodrug or acyclovir oral (3-5X)

Penciclovir- Topical only
Famciclovir- Penciclovir prodrug. Increased oral bioavailability

Vidarabine-trifluidine- topical

Question 24

How are viral inhibition of replication drugs eliminated?

Answer 24

Renally but clearance in neonates is 1/3 of adults

Question 25

How would you treat genital herpes?

Answer 25

Oral acyclovir

Question 26

When would you use intravenous acyclovir?

Answer 26

To treat herpes simplex encephalitis, neonatal HSV infections, and serious HSV or VZA infections (higher doses required for zoster)

Question 27

What would you use to treat HSV keratoconjunctivitis and reccuent epithelial keratitis?

Answer 27

Topical vidarabine and trifluridine

Question 28

Name a drug that inhibits viral penetration.

Answer 28

Docosanol

Question 29

How does docosanol prevent viral penetration?

Answer 29

They prevent the fusion of viral and host membrane. Used topically for orofacial herpes.

Question 30

What drug is used for the treatment of respiratory syncitial virus?

Answer 30

Ribavirin

Question 31

What is ribavirin?

Answer 31

A purine nucleoside analog that inhibits GTP-dependent 5' capping of viral mRNA.

Question 32

What are the pharmacokinetics of ribavirin?

Answer 32

Oral bioavailability good. Hepatic metabolism and renal excretion.

Question 33

What are the adverse reactions of Ribavirin?

Answer 33

Inhalation: fine Oral-systemic: hemolytic anemia TERATOGENIC = NO PREGNANT WOMEN

Question 34

How would you treat hepatitis C

Answer 34

Ribavirin with interferon

Question 35

What is the action of Ganciclovir and Valganciclovir?

Answer 35

Inhibition of viral DNA polymerase. Nucleotide analog.

Question 36

Ganciclovir and Valganciclovir must be phosphorylated in order to become activate. What enzyme phosphorylates these drugs and is it the target for resistance?

Answer 36

The enzyme is Viral protein kinase UL97 and it is the target for resistance.

Question 37

Describe the pharmacokinetics of Ganciclovir and Valganciclovir.

Answer 37

Ganciclovir- IV primarily excreted unchanged via urine | Valganciclovir- prodrug converted to ganciclovir by GI and hepatic enzymes

Question 38

What is the major side effect or concern with using ganciclovir or valganciclovir?

Answer 38

They are myelocuppressive and result in neutropenia and thrombocytopenia

Question 39

What two drugs can be used to treat cytomegalovirus?

Answer 39

Ganciclovir/Valganciclovir and Foscarnet

Question 40

Describe foscarnet.

Answer 40

Inorganic pyrophosphate analog that does not require cellular activation.

Question 41

What is the action of foscarnet?

Answer 41

It inhibits the cleavage of pyrophosphate from deoxxy-TP= block in replication

Question 42

How is foscarnet administered?

Answer 42

IV infusion and is eliminated via the urine

Question 43

What are some of the severe side effects you need to worry about when using foscarnet?

Answer 43

Nephrotoxicity and hypocalcemia can lead to death