Pharmacology: Drugs for Hepatitis

Question 1

What are people who have HBV at risk for?

Answer 1

HCC

hepatocellular carcinoma

Question 2

Interferon alpha class

Answer 2

• used for patients with well compensated liver disease

- who do not wish to be on long term treatment or are planning to be preggo

Question 3

PEG interferones

Answer 3

1x a week as opposed to 3x which is nice

Question 4

MOA of Interferons

Answer 4

changes transcription of UNINFECTED CELLs only

• Tyk2 and JAK1 receptors
• binds, kinases activated, autophosphorylation, attracts STATs
• TF goes to nucleus
• ISG’s are made from DNA

Question 5

Products of ISG?

Answer 5

2’5’ OAS… degrades viral RNA

PKR… inhibits protein synthesis

Question 6

Which T cell phenotype does IFN’s favor?

Answer 6

TH1

• increased inflammation… kills infected liver cells too
• remember that IL-12 makes TH1 cells

Question 7

what are IFN’s dangerousin?

Answer 7

decompensated cirrhosis

-remember that we will damage some liver in the process

Question 8

What drug class can be used regardless of liver status?

Answer 8

nucleosides!

• they just stop transcription or something…. competitive inhibitors… inserted into DNA and then the cell dies
• just like with HIV

Question 9

Name the nucleosides

Answer 9

Lamivudine
Telbivudine
Entecavir
Tenofivir (already a monophosphate)… remember that the host cell does that first phosphorylation… main route of resistance

Question 10

First line oral anti-HBV agents

Answer 10

Tenofivir and entecavir

Question 11

What is an adverse event of tenofivir?

Answer 11

Nephrotoxicity

-proximal renal tubule may be particularly susceptible

Question 12

Which drug has a lot of HBV resistant to it?

Answer 12

Lamivudine

-so, it’s not a first line agent

Question 13

What do we add to IFN to treat HCV?

Answer 13

ribavirin

Question 14

MOA of ribavirin?

Answer 14

gets P’ed

• mono P stops IMP dehydrogenase… no purine synthesis
• Tri P stops TNA-dependent RNA polymerase…
• potentiates IFN action… alters Th1 balance as well

Question 15

How does the body get rid of Ribavirin

Answer 15

• hepatic metabolism
• gets avidly taken up by RBCs
• stays in there for 40 days

Question 16

Ribavirin contraindications

Answer 16

hemolytic anemia….

pregancy… may cause birth defects… they have to take pregancy prior to, during, and 6months after this shit

Question 17

What is Simeprevir?

Answer 17

Protease inhibitor

Question 18

What is Ledipsasvir?

Answer 18

NSSA inhibitor

Question 19

What is Sofosbuvir?

Answer 19

Polymerase inhibitor