Viral hepatitis 3 Flashcards
What are the drugs used to treat HCV?
Ribavirin
Telaprevir
Boceprevir
PEG-IFN alfa
What is the MOA of IFN alfa?
Binds to cell surface receptor and stimulates production of Endoribonucleases that cleave viral RNA, inhibition of viral penetration and uncoating, and enhanced lytic effects of T lymphocytes
Why are drugs like IFN alfa pegylated?
Pegylation increases the serum half life of the drug. Allows for once weekly dosing
What adverse effects are associated with IFN-alfa?
Neurophsychiatric issues (dose limiting)
myelosuppression
Flu-like illness upon injection
What is the treatment for chronic HCV genotype 1?
PEG-IFN-alfa
Ribavirin (24-48 wks)
Telaprevir or Boceprevir (protease inhibitors)
What is the treatment for chronic HCV genotypes 2 and 3?
PEG-IFN-alfa
Ribavirin (24-48 wks)
What are the MOAs of ribavirin?
Enhanced T-cell immune clearance
Inhibition of IMPDH (depletes necessary GTP)
direct inhibition of viral RNA polymerase
Synergizes well with IFN
Should ribavirin be taken with food or without?
Take with food to increase bioavailability
What are the adverse effects of ribavirin?
Hemolytic anemia (10-13%)(primary toxicity)
Myocardial infarction
Male and female teratogenicity
What is the mechanism of action for Telaprevir and Boceprevir?
They are NS3/4A serine protease inhibitors
Which mutations confer a high level of resistance to Boceprevir and Telaprevir?
NS3-R155K/T
NS3-A156S/T/V
What adverse effects are associated with Boceprevir and Telaprevir?
Fatigue
anemia (most common)
Nausea
What serious adverse effects are associated with Telaprevir?
Serous rash: DRESS Steven-Johnson syndrome Toxic epidermal necrolysis Erythema multiforme
What is the ADME of boceprevir and telaprevir?
Take both with food
Both bind plasma proteins
Both undergo hepatic metabolism
Both eliminated in stool
What is the metabolism of Telaprevir?
substrate and inhibitor of CYP3A4 and P-gp
Inhibitor of OATP1B1, and OATP2B1
