Anti Viral Agents

Question 1

Antivirals that work through host cell kinases.

Answer 1

AZT(Zidovudine) and nucleoside analogues – phosphorylated by cell kinases. Turns to nucleotides that

Question 2

Antivirals that work through viral kinases.

Answer 2

Acyclovir (Thymidine Kinase) and Gancyclovir (CMV protein kinase, UL97) – first phosphorylated by viral kinases.

Question 3

Why is Acyclovir more selectively toxic than other antivirals?

Answer 3

because it is phosphorylated by Thymidine kinase a viral kinase.

Question 4

Three viruses that Acyclovir can be used against.

Answer 4

Herpes simplex, Epstein Barr, and VZV

Question 5

Two indications for Valacyclovir.

Answer 5

L-valine ester prodrug of acyclovir. Recurrent genital herpes, zoster infections (shingles).

Question 6

Three indications for Famciclovir.

Answer 6

Oral prodrug of Penciclovir. Acute Herpes Zoster, suppression of recurrent genital herpes.

Question 7

Early symptoms and DOC for Herpes Encephalitis.

Answer 7

Acute onset of fever, headache, decreased consciousness and seizures. Acyclovir

Question 8

How Ganciclovir is metabolized to an active form inside the host cells.

Answer 8

Guanosine analogue – phosphorylated first by virus then 2nd and 3rd by Host cell. Forms Nucleotide that inhibits CMV.

Question 9

How Cidofovir has selective toxicity.

Answer 9

Cytosine analog. 1000X more effective against viral DNA-polymerase than host DNA polymerase. Reno toxic – coadministered with Probenecid.

Question 10

What is unique about the metabolism requirement for Foscarnet?

Answer 10

Inhibits viral DNA-polymerase, RNA-polymerase, and HIV-RT directly – no activation by phosphorylation required.

Question 11

Four viruses treatable by Foscarnet?

Answer 11

Herpetics, Hep B, and HIV

Question 12

Viral replication

Answer 12

Attachment. Entry through membrane. Uncoating of Genetic material. Synthesis of early regulatory proteins. Synthesis of RNA/DNA. Synthesis of late structural proteins. Assembly/maturation of viral particles. Release from host.

Question 13

CDC guideline Tx for influenza in Adults.

Answer 13

Rimantadine for adults only. Zanamivir is apropriate if older than 7.

Question 14

MOA of neuraminidase inhibitors.

Answer 14

Inhibit viral cleavage of sialic acid – inhibits the release of newly formed viruses. (Zanamivir and Oseltamivir)

Question 15

Site of action for Palivizumab

Answer 15

Binds to fusion protein of RSV. Prevents infection of host cell – reduce replication and spread.

Question 16

Dosing and timing of Paluvizumab for RSV(Respiratory Syncytial Virus)

Answer 16

15mg/Kg given IM monthly x up to 5 doses during RSV season.

Question 17

Who should avoid contact with patients using Ribavirin? Why?

Answer 17

Those at risk of becoming pregnant. Inhaled teratogenic.

Question 18

Why is selective toxicity more difficult with viruses than with bacteria?

Answer 18

fewer differences between viral and host machinery to exploit – viruses tend to use the host mechanics. Also broad variety of heterogenous agents.

Question 19

Difficulties in developing drugs against viruses.

Answer 19

heterogenous nature of viruses makes it hard to come up with a broad treatment antiviral.

Question 20

Three indications for Acyclovir

Answer 20

Mucocutaneous herpetic lesions, genital herpes lesions, and prophylaxis in AIDS and other immunocompromised patients.

Question 21

Two blood related adverse effects of ganciclovir.

Answer 21

Leukopenia and Thrombocytopenia

Question 22

What could be monitored to determine the duration of Foscarnet action?

Answer 22

Kidney clearance is directly proportionate to creatinine clearance.

Question 23

Major toxicity of Zanamavir and contraindications.

Answer 23

Bronchospasm. Not for pts with underlying airway disease (COPD, Asthma)