[PHARM] Viral Hepatitis Pharmacology

Question 1

What is the goal for treatment of HBV?

Answer 1

Slow the development of liver disease

Can prevent from progressing to hepatocellular carcinoma

Question 2

Define:

Chronic active hepatitis

Answer 2

Acute hepatitis state that continues without normal recovery (longer than 6-12 months)

Question 3

What do interferons do within the body?

Answer 3

Interferons are host cytokines that exert complex

antiviral, immunomodulatory and antiproliferative actions

Question 4

What are the (technically 3) types of interferons used to treat hepatitis?

Answer 4

Inferferon alpha-2b

PEGylated interferon alpha-2b

PEGylated interferon alpha-2a

*The PEGylated interferons are basically the same for our purposes

Question 5

When would you give an interferon drug?

Answer 5

Treatment of patients with well compensated liver disease

Question 6

You should NOT give interferons if your patient….

Answer 6

Is planning to be pregnant within 2-3 years

***DANGEROUS to give to patients in decompensated cirrhosis

Question 7

What are the differnces in duration of action of inferferon alpha 2-b VERSUS PEGylated interferons alpha2a/2b?

Answer 7

Inferferon alpha 2b doesn’t last as long as PEGylated interferons

Question 8

What are the 3 primary functions of interferons in surrmounting an immune response?

Answer 8

1. Protect nearby healthy cells
2. Signal macrophages and NK cells to clear infection
3. Lysosome lysis, lysis of infected cell

Question 9

What is the MOA of interferon alpha?

Answer 9

Interferon alpha binds to JAK1 and TYK2 which activates them

This causes STAT1 and STAT2 to become active (phosphorylated) and induce the activation of transciption of interferon stimulated genes (ISGs)

Question 10

What are the adverse effects that occur with interferon alpha/PEGylated interferons?

Answer 10

80-90% of patients experience SOME kind of adverse effect

FLU LIKE SYNDROME

Fatigue and mental depression

Question 11

What are the dose limiting toxicities associated with interferon alpha/PEGylated interferon?

Answer 11

Bone marrow suppression

Neurotoxicity-behavioral changes

Question 12

What is the MOA of nucleosides/nucleotides treatment for HBV?

Answer 12

HBV DNA reverse transciptase/DNA polymerase inhibitors

Question 13

How do you take nucleosides/nucleotides for treatment of HBV?

Answer 13

ORALLY

*much easier to take than the interferon drugs

Question 14

What drugs would you use for a patient that has decompensated cirrhosis?

Answer 14

Nucleoside/nucleotides

Question 15

What are the (3) nucleoSIDE drugs?

Answer 15

Lamivudine

Telbivudine

Entecavir

Question 16

What is are the two nucleoTIDE drugs?

Answer 16

Tenofovir

Adefovir

Question 17

Which one has the monophosphate attached?

Nucleosides?

Nucleotides?

Answer 17

NucleoTIDES!!! have the monophosphate group

Question 18

What is the first line treatment for wild-type HBV?

Answer 18

Tenofovir

Question 19

What is the unique AE of tenofovir?

Answer 19

Nephrotoxicity

Question 20

What category drug is tenofovir in?

Answer 20

Nucleotide analog of adenosine

Question 21

What is the first line treatment of HBV in patients that have renal insufficiency?

Answer 21

Entecavir

Question 22

What are the TAKE HOME MESSAGES for HBV treatment?

Answer 22

• Therapies for HBV fail to fully eradicate the virus
• RELAPSE of hepatitis induced by HBV is always possible

Question 23

What are the interferon drugs?

Answer 23

Interferon alpha2b

PEGylated interferon alpha 2b

PEGylated interferon alpha 2a

Question 24

What category is lamivudine in?

Answer 24

Nucleoside

Question 25

What category is **telbivudine** in?

Answer 25

Nucleoside

Question 26

What category is **entecavir** in?

Answer 26

Nucleoside

Question 27

What category is **tenofovir** in?

Answer 27

Nucleotide

Question 28

What cateogory is **adefovir** in?

Answer 28

Nucleotide

Question 29

Which can be cured? HBV or HCV?

Answer 29

HCV \*remember: H**C**V has a C in it, so it can be **CURED**

Question 30

What is the primary drug used for HCV (historically)?

Answer 30

Ribavirin

Question 31

What are the 3 things that **ribavirin** does therapeutically?

Answer 31

1. Interferes with **synthesis** of **GTP** 2. Inhibits **capping** of **viral mRNA** 3. Inhibits the viral **RNA dependent** polymerase

Question 32

Contraindications for **ribavirin?**

Answer 32

Anemia Pregnancy

Question 33

What do the NEW treatments for **HCV infection** primarily target?

Answer 33

Translation and Processing

Question 34

What are the (3) **NS 3/4A protease inhibitors?**

Answer 34

Grazoprevir Paritaprevir Simeprevir

Question 35

Which drug within the **NS 3/4Aprotease inhibitors** has CYP34a drug interactions and has the AE of **nausea, pruritis** and **insomnia?**

Answer 35

Paritaprevir

Question 36

Which of the three **NS 3/4A protease inhibitors** needs to be taken with food?

Answer 36

Simeprevir

Question 37

What are the two drugs that are **NS5B RNA polymerase inhibitors?**

Answer 37

Dasabuvir Sofosbuvir

Question 38

Which **NS5B RNA polymerase inhibitor** is a prodrug?

Answer 38

Sofosbuvir

Question 39

Which **NS5B RNA polymerase inhibitor** has drug-drug interactions with CYP3A and AE of **nausea, pruritus and insomia?**

Answer 39

Dasabuvir

Question 40

What are the 4 **NS5A inhibitors?**

Answer 40

Elbasvir Ledipasvir Ombitasvir Velpatasvir

Question 41

What is the common ending for **NS3/4A inhibitors?**

Answer 41

-Previr Grazo**previr** Parita**previr** Sime**previr**

Question 42

What is the common ending for **NS5B inhibitors?**

Answer 42

Dasa**buvir** Sofos**buvir** \*REMEMBER, if you are treating NS5**B**, you add a **B** in front

Question 43

What is the common ending for **NS5A inhibitors?**

Answer 43

-asvir Elb**asvir** Ledip**asvir** Ombit**asvir** Velpat**asvir** \*REMEMBER, if you are treating NS5**A,** remember to have an **A**