Hepatitis Drugs

Question 1

Goals for hepatitis B treatment

Answer 1

• virus will not be fully eradicated and relapse is possible even if therapy is successful
• goal is to slow cirrhosis and hepatocellular carcinoma development

Question 2

MOA interferons

Answer 2

• activate JAK1 and TYK2
• phosphorylated receptor leads to activation of STAT 1/2
• these go to the nucleus and transcribe interferon stimulated genes
• these inhibit viral protein synthesis

Question 3

Indications for interferons

Answer 3

used in well compensated liver disease, don’t want long term treatment (may be want to get pregnant in 2-3 years)

Question 4

interferon with short half life (+frequency of administration)

Answer 4

interferon alpha-2b (must be given every 36 hours)

Question 5

interferons with longer half life

Answer 5

1) PEGylated interferon α-2b

2) PEGylated interferon α-2a

Question 6

adverse effects of interferons

Answer 6

80% of patients have flu-like syndromes, bone marrow suppression, and neurotoxicity. Improve with continued therapy

Question 7

Initial reaction to interferons

Answer 7

leads to a flare of hepatitis (good sign)

Question 8

Contraindications interferons

Answer 8

• dangerous in decompensated cirrhosis (flare will make liver disease much worse)
• don’t use with patients wanting to be pregnant soon

Question 9

nucleoside drugs (3)

Answer 9

• Lamivudine
• telbivudine
• Entecavir

Question 10

Nucleotide drugs (2)

Answer 10

• Tenofivir

- Adefovir

Question 11

MOA Nucleoside and Nucleotides

Answer 11

incorportated into viral DNA to block transcription of hepatitis B virus (HBV DNA reverse transciptase/DNA polymerase inhibitors)

Question 12

First line nucleoside/nucleotide for HBV infection

Answer 12

Entecavir (guanosine analog)

Question 13

First line nucleoside/nucleotide for HBV infection if resistant to nucleosides

Answer 13

Tenofovir

Question 14

Suffix Nucleotides

Answer 14

-fovir

Question 15

Adverse effects tenofovir

Answer 15

nephrotoxicity (proximal renal tubule)

Question 16

Highlights nucleoside/nucleotide drugs (3)

Answer 16

• oral agents that suppress HBV
• better tolerated and higher response rate than interferon Tx
• can be used in patients with decompensated cirrhosis

Question 17

What HBV drug (nucleoside/nucleotide) is better for renal insufficiency patients?

Answer 17

nucleosides (entecavir)

Question 18

Factors influencing selection for nucleotide/sides for HBV treatment

Answer 18

• resistance profile
• efficacy (clearance of HBV DNA)
• usefulness with HIV co-infection

Question 19

Do therapies for HBV fully eradicate the virus?

Answer 19

NO, relapse is always possible, even with therapy

Question 20

nucleoside for HCV used in concert with PEG interferons to potentiate their action

Answer 20

Ribavirin (guanosine analog)

Question 21

Suffix NS3/4A inhibitors

Answer 21

-previr

Question 22

Suffix NS5B inhibitors

Answer 22

-buvir

Question 23

Suffix NS5A inhibitors

Answer 23

-asvir

Question 24

Treatment for patients with both HBV and HCV

Answer 24

treatment directed at predominant virus

Question 25

Contraindications Ribavirin

Answer 25

anemia and pregnancy (specific regimen listed out months tests and 2 forms of birth control)

Question 26

MOA grazoprevir, paritaprevir, simeprevir

Answer 26

inhibit NS3/4A serine protease

Question 27

Adverse interactions paritaprevir

Answer 27

CYP3A, drug-drug interaction

Question 28

Special instructions for Simeprevir use

Answer 28

must be taken with food to maximize absorption

Question 29

MOA dasabuvir, sofobuvir

Answer 29

inhibit NS5B RNA polymerase (polymerase is highly conserved so it is effective against all 6 HCV genotypes)

Question 30

interactions dasabuvir

Answer 30

CYP3A, drug-drug interactions

Question 31

Interactions elbasvir, ombitasvir

Answer 31

CYP3A

Question 32

First once-daily single-tablet regimen with pangenotypic activity

Answer 32

Velpatasvir + sofosbuvir

Question 33

nucleoside vs nucleotide

Answer 33

nucleoside: -OH group nucleotide: phosphate group

Question 34

Can HCV be cured?

Answer 34

Yes, because it is RNA and not incorporated into the host DNA