Pharm Anti-virals

Question 1

Acyclovir (Spectrum)

Answer 1

Anti-viral (15-21% bioavailability)

Herpes simplex (HSV) 1 and 2
Varicella-zoster (VZV)
EBV

Not CMV

Question 2

Famciclovir (Spectrum)

Answer 2

Anti-viral (77% bioavailability)

Herpes simplex (HSV) 1 and 2
Varicella-zoster (VZV)
EBV

Not CMV

Question 3

Ganciclovir (Spectrum)

Answer 3

Active against cytomegalovirus (CMV)

Poor bioavailability (5-9%)

Question 4

Foscarnet (Spectrum)

Answer 4

Anti-viral

GCV resistant CMV,
ACV-resistant HSV 1&2, VZV
Intolerable myelosuppression with GCV

Question 5

Valacyclovir

Answer 5

Prodrug of Acyclovir combined with valine

Improved bioavailability to 54% but 5x more expensive

Question 6

Famciclovir

Answer 6

Prodrug of penciclovir

Improved oral bioavailability over ACV of 77%

Oral treatment of VZV

Question 7

Valaganciclovir

Answer 7

Prodrug, valine ester of Ganciclovir

Improved bioavailability to 60%

Question 8

Foscarnet (MOA)

Answer 8

Inorganic pyrophosphate analog

Directly inhibits viral DNA polymerase (Reversibly blocks pyrophosphate binding site of viral DNA polymerase)

Renal metabolism

Question 9

Acyclovir (MOA)

Answer 9

Deoxyguanosine nucleotide analog that inhibits transcription by viral DNA polymerase

Renal metabolism

Question 10

Ganciclovir (MOA)

Answer 10

Deoxyguanosine nucleotide analog that inhibits transcription by viral DNA polymerase

Renal metabolism

Question 11

Acyclovir (Toxicity)

Answer 11

Rare, not significant
Nephrotoxicity: can crystallize in renal tubules
Neurotoxicity: lethargy, confusion, delirium

Question 12

ACV Resistance

Answer 12

Due to loss of viral thymidine kinase, altered TK activity, or DNA polymerase mutants

ACV-R HSV or VSV will be cross-resistant to famciclovir and ganciclovir

Question 13

Ganciclovir (Toxicity)

Answer 13

Myelosuppression (Neutropenia and thrombocytopenia)
CNS toxicity (Headache, change in mental status)

Question 14

Ganciclovir Resistance

Answer 14

Reduced intracellular phosphorylation due to point mutations/deletions in the UL97 gene

Point mutations in the viral DNA polymerase

Cross resistance to Foscarnet

Question 15

Foscarnet (Toxicity)

Answer 15

Very significant

Nephrotoxicity (usually 2nd week of therapy)
- Reversible

Metabolic abnormalities

• Hypocalcemia
• Hypomagnesemia
• Hypokalemia

CNS abnormalities
- Headache, irritability, seizures

Painful genital ulcerations

Question 16

Hep B Therapy Drugs

Answer 16

Lamivudine/emtricitabine (Least potent)
Entecavir
Tenofovir (Most potent)

Question 17

Hep B Drugs (MOA)

Answer 17

Nuceloside analogs: inhibits hepatitis B DNA polymerase via chain termination

Suppresses replication, not a cure

Question 18

Interferon alpha 2a or 2b (MOA)

Answer 18

Hep C

Induce interferon-stimulated genes which establish an antiviral state within cells, though the response is not virus specific; inhibit viral protein synthesis

Question 19

Interferon alpha 2a or 2b (Side effects)

Answer 19

• Fever, myalgia
• Neutropenia, thrombocytopenia
• Hypothyroidism
• Depression

Question 20

Ribavirin (MOA)

Answer 20

Hep C

Nuceloside analog

Question 21

Ribavirin (Side effects)

Answer 21

• Hemolytic anemia
• Teratogenic
• Flu-like symptoms
• Depression/irritability
• Rash
• Nausea/diarrhea

Question 22

Interferon + ribavirin (response rates)

Answer 22

Most responsive to least:
2 and 3
4
5
6
1

Question 23

Interferon + ribavirin (Limitations)

Answer 23

Not well tolerated
Poor response rates
Long duration of therapy (up to 48 weeks)

Question 24

Hep C Direct Acting Agents

Answer 24

Protease inhibitors

• Boceprevir
• Telaprevir
• Simeprevir

Only used for Genotype 1

Question 25

Protease Inhibitors benefits

Answer 25

Increase response rates of Interferon and ribavirin therapy Decreased length of therapy

Question 26

Harvoni (MOA)

Answer 26

Sofosbuvir (Nucleoside analog against HCV NS5B polymerase) Ledipasvir (NS5A inhibitor)

Question 27

Harvoni (Spectrum)

Answer 27

HCV genotypes 1, 4, 5, and 6

Question 28

Zapatier (MOA)

Answer 28

Elbasvir (NS5A inhibitor) | Grazoprevir (NS3/NS4A inhibitor)

Question 29

Zapatier (Spectrum)

Answer 29

HCV Genotypes 1 and 4

Question 30

Epclusa (MOA)

Answer 30

Sofosbuvir (Nucleoside analog against HCV NS5B polymerase) | Velpatsavir (NS5A inhibitor)

Question 31

Epclusa (Spectrum)

Answer 31

Pan-Genotypic | HCV Genotypes 1, 2, 3, 4, 5, 6

Question 32

Mayret (MOA)

Answer 32

Glecabrevir (NS3/4A protease inhibitor) | Pribrentasvir (NS5A inhibitor)

Question 33

Mayret (Spectrum)

Answer 33

Pan-Genotypic | HCV Genotypes 1, 2, 3, 4, 5, 6