Antiviral Drugs

Question 1

What Herpes viruses is acyclovir indicated for? Which is it not?

Answer 1

Indicated for Herpes family (1&2), Varicella

Not indicated for Epstein Bar

Question 2

What is the MOA for Acyclovir?

Answer 2

Prodrug converted to acyclo-guanidine triphosphate by viral thymidine kinase. Sequentially phosphorylated by cellular enzymes to acyclo-GTP
Inhibits viral DNA polymerase and is incorporated into DNA resulting in chain termination

Question 3

Does Acyclovir (Acyclo-GTP) target human DNA polymerases?

Answer 3

It is more selective for viral DNA polymerases but can have some effect

Question 4

What type of inhibitor is Acyclo-GTP for viral DNA polymerase?

Answer 4

Competitive

Question 5

What does Acyclo-GTP lack that results in chain termination?

Answer 5

The 3’ hydroxyl group

Question 6

What is the mechanism of drug resistance to acyclovir?

Answer 6

1) Decreased viral expression of thymidine kinase
2) Mutation of thymidine kinase, selection of viruses that do not activate acyclovir
3) Mutation and selection for viral DNA polymerases that are not inhibited as well by acyclo-GTP

Question 7

What two routes are tolerated well by acyclovir? What are adverse effects of each?

Answer 7

Topical - burning sensation

Oral - nausea, diarrhea, headache, vertigo

Question 8

What are adverse effect of acyclovir when given for shingles? When given IV?

Answer 8

Shingles - tiredness

IV - reversible renal damage

Question 9

Have can renal damage be avoided when giving acyclovir intravenously?

Answer 9

Avoiding rapid infusion

Adequate hydration

Question 10

What is the major contraindication for Acyclovir?

Answer 10

Avoid other IV nephratoxic drugs

Question 11

What two other drugs could be used to treat Herpes? What features make them better and/or worse?

Answer 11

Valacyclovir - prodrug of acyclovir, better oral availability
Famiciclovir - prodrug of penciclovir (topical only drug), better oral availability

Question 12

What are 5 topical drugs for ocular herpes?

Answer 12

Ganciclovir or Acyclovir
Trifluridine
Brivudine
Vidarabine

Question 13

What is the indication, MOA, and adverse effects for Trifluridine?

Answer 13

Indication: Ocular infections with HSV 1 or 2
MOA: inhibits viral DNA synthesis
Adverse Effects: burning and stinging, edema of eyelid, not absorbed systemically

Question 14

What is the indication, MOA, and adverse effects of Vidarabine?

Answer 14

Indication: Acute keratoconjunctivitis or recurrent epithelial keratitis caused by HSV 1 or 2
MOA: Inhibits DNA syntheis
Adverse effects: Burning and stinging

Question 15

What is the primary indication for ganciclovir? Why would it be used prophylactically? What are two methods of availability?

Answer 15

Indication: CMV infections
Prophylactic use in organ transplant patients
Availability: Oral and IV

Question 16

What is a contraindication for ganciclovir?

Answer 16

Pregnancy

Question 17

What viral enzyme works on ganciclovir instead of viral thymidine kinase?

Answer 17

Viral deoxyguanosine kinase

Question 18

What enzymes are expressed at high levels in CMV and HSV infections that catalyze the formation of ganciclovir diphosphate and ganciclovir triphosphate?

Answer 18

Cellular kinases

Question 19

What is the method of action for GCV-5’ triphosphate?

Answer 19

Inhibits viral DNA polymerase

Chain termination

Question 20

What are the adverse effects of ganciclovir? What is the contraindication?

Answer 20

Granulocytopenia and Thrombocytopenia

Contraindicated with zidovudine

Question 21

What three other drugs are approved for CMV?

Answer 21

Valganciclovir (prodrug of ganciclovir)
Cidofovir
Foscarnet

Question 22

What is the second line drug used for CMV retinitis that also was the first anti-sense drug?

Answer 22

Fomivirsen

Question 23

What is the adverse effect that makes Fomivirsen a second line drug for CMV retinitis? What drug interaction can suppress this reaction?

Answer 23

Ocular inflammation

Can be suppressed with glucocorticoids

Question 24

Which two Hepititis viruses have vaccines? Which two are there drugs for?

Answer 24

Vaccines for A and B

Drugs for B and C

Question 25

What are the 4 hepatitis antivirals indicated for hepatitis B? Which two are more effective? Which two are less effective? What do they all inhibit?

Answer 25

More effective: Entecavir and Tenofovir Less effective: Lamivudine and Adefovir Hepatitis B reverse transcriptase

Question 26

What is the MOA for entecavir?

Answer 26

A prodrug converted to entecavir tri-phosphate, inhibiting Hep B reverse transcriptase Incorporation into viral DNA by reverse transcriptase results in DNA chain termination

Question 27

Which Hep B drug is also used for HIV? Which disease requires a lower dose?

Answer 27

Tenofovir | Hep B

Question 28

What are two reasons to use combination drug treatment?

Answer 28

Better blocking of viral replication | Drug resistance is less likely to arise

Question 29

What are the 5 classes of drugs for Hep C?

Answer 29

``` Viral protease inhibitors (Simeprevir) Viral RNA polymerase inhibitors (chain termination) (Sofosbuvir) NS5A protein inhibitor (Ledipasvir) Pegylated Interferon Ribavirin ```

Question 30

What drug inhibits HCV NS3/4A protease?

Answer 30

Simeprevir

Question 31

What does the triphosphate derivative of Sofosbuvir mimic so it can be incorporated into the elongating RNA primer by HCV RNA polymerase, resulting in chain termination?

Answer 31

Cellular uridine

Question 32

Is sofosbuvis a pro-drug? What is it a substrate for?

Answer 32

Yes, substrate for RNA polymerase

Question 33

NS5A protein plays a vital role in what part of Hep C viral activity? What two drugs act as inhibitors?

Answer 33

Viral replication, assembly, and secretion | Lepipasvir and Ombitasvir

Question 34

What adverse symptoms make pegylated interferon a less desired drug for Hep C?

Answer 34

Flu like symptoms | Thus, it rarely is used anymore

Question 35

What drug for Hep C can cause hemolytic anemia and is not effective when used alone?

Answer 35

Ribavarin

Question 36

Which three drugs are most widely used in combination to treat Hep C?

Answer 36

Simeprevir, Sofosbuvir, Ledipasvir

Question 37

People over what age should get a flu vaccine?

Answer 37

6 months

Question 38

What two classes of drugs treat the flu? Do they work well?

Answer 38

Adamantanes and Neuraminidase inhibitors | No, they usually only reduce hospital time or symptom time

Question 39

Which drugs treat influenza A and not influenza B? MOA? Availability? Adverse effects?

Answer 39

Amantadine and Rimantadine (Adamantanes) Inhibit viral M2 protein channels which inhibits proton influx and uncoating of virus Oral CNS effects, dizziness, nervousness, insomnia

Question 40

Which two neuraminidase inhibitors treat the flu? Which should not be used in asthma patients?

Answer 40

Oseltamivir and Zanamivir | Zanamivir - not to use in asthma patients

Question 41

When must oseltamivir and Zanamivir be given in order to improve outcome?

Answer 41

Within 2 days of symptoms

Question 42

What is the MOA of neuraminidase inhibitors?

Answer 42

Cleaves sialic acid residues on host cells which are required for release of the virus progeny. Promotes clumping.