Antiviral Drugs

Question 1

How would you administer Acyclovir for someone who presents with genital herpes (HSV-2)?

Answer 1

orally

Question 2

How would you administer Acyclovir for someone who presents with herpes infection of face and mouth?

Answer 2

orally; usually reserved for immunocompromised patients

Question 3

When is IV acyclovir used?

Answer 3

for immunosuppressed patients with chicken pox or with shingles

Question 4

MOA for Acyclovir

Answer 4

1. prodrug converted to acyclo-guanidine triphosphate (active) by thymidine kinase
2. sequential phosphorylation by cellular enzymes to acyclo-GTP
3. acyclo-GTP inhibits viral DNA polymerase, and is incorporated into viral DNA resulting in chain termination –> replication is blocked

Question 5

Is acyclo-GTP more selective for viral or human DNA polymerases?

Answer 5

viral

Question 6

What are 3 mechanisms of drug resistance for acyclovir?

Answer 6

1. thymidine kinase mutation (viruses that do not activate acyclovir)
2. decreased viral expression of thymidine kinase
3. mutation and selection of viral DNA pol that are not inhibited as well by acyclo-GTP

Question 7

What are adverse effects of topical and oral administration of acyclovir? IV?

Answer 7

1. topical - transient burning sensation
2. oral - nausea, diarrhea, HA, vertigo
3. reversible kidney damage that presents with high creatine and urea levels

Question 8

How can kidney damage be minimized during IV administration of acyclovir?

Answer 8

1. slow infusion (1hour)
2. adequate hydration
3. avoiding co-administration with other nephrotoxic drugs

Question 9

What is a contraindication for acyclovir administration?

Answer 9

avoiding IV co-administration with other nephrotoxic drugs

Question 10

What is the active form of acyclovir?

Answer 10

acyclovir triphosphate

Question 11

What are 2 other drugs for herpes that are prodrugs of acyclovir?

Answer 11

1. valacyclovir
2. famiciclovir

*both have better oral availability

Question 12

What are topical drugs for ocular herpes?

What do they all have in common?

Answer 12

1. ganciclovir or acyclovir
2. trifluridine
3. brivudine
4. vidarabine

inhibit viral DNA synthesis

Question 13

When would you administer vidarabine?

Answer 13

acute kertoconjunctivitis and recurrent keratitis caused by HSV 1 or 2

Question 14

Which topical drug for ocular herpes causes edema of the eyelid in 3% of patients and is not absorbed systemically?

Answer 14

trifluridine

Question 15

Ganciclovir is a drug for _____. Availability? Adverse effects?

Answer 15

cytomegalovirus

available orally and IV

granulocytopenia and thrombocytopenia; should not be used during pregnancy

Question 16

Ganciclovir is approved for prophylactic use in _____.

Answer 16

organ transplant patients

Question 17

Describe the MOA of ganciclovir.

Answer 17

1. converted to monophosphate by viral deoxyguanosine kinase (in CMV infected cells)
2. cellular kinases convert to triphosphate
3. ganciclovir triphosphate inhibits viral DNA polymerase (more selectively the human pol) and incorporates into the DNA resulting in chain termination —> viral replication blocked

Question 18

What are contraindications of ganciclovir?

Answer 18

1. coadministration with zidovudine exacerbates granulocytopenia and thrombocytopenia
2. coadministration with G-CSF can reduce granulocytopenia

Question 19

What are other drugs for CMV? (x3) Give some facts about each.

Answer 19

1. valganciclovir (prodrug of ganciclovir)
   - better oral availability; just as effective for CMV retinitis as IV ganciclovir
2. cidofovir
   - approved for only one indiction (CMV retinitis in AIDS patients)
   - MOA converted to diphosphate and inhibits viral DNA pol
3. foscarnet
   - approved uses are CMV retinitis in AIDS patients
   - nephrotoxic

Question 20

What is the clinical use of Fomivirsen?

Answer 20

CMV retinitis in patients that do not respond to another drug

Question 21

MOA for Fomivirsen

Answer 21

antisense drug

inhibits the replication of CMV by binding to the complimentary sequence of mRNA transcribed by CMV; inhibits synthesis of proteins that are essential for production of infection CMV

Question 22

What an adverse effect of Fomivirsen

Answer 22

ocular inflammation

Question 23

For which Hepatitis is there not a vaccine for?

Answer 23

Hep C

Question 24

What is the preferred drug for Hep B?

Answer 24

Entecavir

Question 25

Drugs for Hep B are ______ and inhibit _______.

Answer 25

nucleoside analogs that inhibit Hep B reverse transcriptase

Question 26

What are the effects of Lamivudine on Hep B infections?

Answer 26

1. suppresses viral réplication (but is not a cure) 2. reduces liver inflammation 3. long term use leads to resistance

Question 27

What is the active form of entecavir and what does it do?

Answer 27

lamivudine triphosphate - incorporates into viral DNA by HBV reverse transcriptase resulting in DNA chain termination

Question 28

What is the prodrug of tenofovir for Hep B?

Answer 28

tenofovir disoproxil

Question 29

Tenofovir is an NRTI. What does NRTI stand for?

Answer 29

nucleotide analog reverse transcriptase inhibitor

Question 30

_______ is used for both HIV and Hep B

Answer 30

tenofovir

Question 31

Hep C and HIV require _____ drug treatment for two reasons:

Answer 31

combination drug treatment bc: 1. better blocking of viral replication - wha the first drug doesn't block may be blocked by the second drug 2. drug resistance is less likely to arise

Question 32

What are the 3 current drugs for Hep C? (older ones were PEG-IFN and ribavirin) which step in replication does each drug inhibit?

Answer 32

1. viral protease inhibitors (Simeprevir) - inhibits translation/processing 2. Viral RNA polymerase inhibitors / chain termination (Sofosbuvir) - inhibits replication 3. NS5a protein inhibitor (Ledipasvir) - inhibits morphogenesis; NS5A protein plays important role in viral rep, assembly, secretion

Question 33

What is the adverse effect of PEG-IFN?

Answer 33

flu like sxs (bc interferon alpha binds to receptors of infected cells) and depression

Question 34

What is an adverse effect of ribavirin?

Answer 34

hemolytic anemia

Question 35

What are the two types of vaccines available for influenza A and B?

Answer 35

inactivated influenza vaccine attenuated live vaccine (intranasal spray)

Question 36

What are the two classes of drugs for influenza?

Answer 36

1. Adamantanes - amantadine and rimantadine 2. neuraminidase inhibitors - oseltamivir (tamiflu) and zanamivir (relenza)

Question 37

In the influenza virus, amantadine blocks ____ and neuraminidase blocks ______.

Answer 37

amantadine blocks proton channel neuraminidase blocks budding

Question 38

True or false: amantadine and rimantadine are active against Influenza A but not against Influenza B.

Answer 38

true

Question 39

What is the MOA for amandine/rimantadine

Answer 39

inhibit viral M2 proton channels, virus taken up by endosomes - viruses cannot acidify and uncoat

Question 40

Which neuraminidase inhibitor should not be used in asthma patients to treat influenza?

Answer 40

zanamavir

Question 41

What are used for prophylaxis of family members/nursing home patients?

Answer 41

neuraminidase inhibitors such as oseltamivir (tamiflu) and zanamivir (relenza)

Question 42

What is the MOA for neuraminidase inhibitors?

Answer 42

normally, neuraminidase catalyzes cleavage of silica acid residues on the surface of host cells and influenza virus - required for release of viral progeny neuraminidase inhibitors block this - inhibitors are analogs of silica acid

Question 43

Must begin treatment of neuraminidase inhibitors within _______ of sxs to improve outcomes.

Answer 43

within 2 days of symptoms