HBV/HCV antivirals Flashcards
IFNa
tx w/ well compensated liver disease Shorter course (24-48 weeks) good efficacy resistance is rare Side effects include flu like symptoms dangerous in decompensated liver PEGylated INF has longer DOA
IFNa MOA
activates JAK/STAT signaling
activates transcription of IFN stimulated genes
ISG’s inhibits viral replication at many steps
Depends on immune clearance of HBV infected cells
-increased inflammation and fibrosis
-PEGylated induces increased ALT during seroconversion
adverse effects and contraindications of IFNa
dangerous in decompensated liver disease
flu-like symptoms
bone marrow suppression
neurotoxicity
Nucleosides/tides
reverse transcriptase/polymerase inhibitors
better tolerated than IFNa
higher response than IFNa
can be used in decompensated pts
NucleoTIDE triphosphate is active agent
- converted by cellular kinases
- impaired kinase activity leads to resistance
nucleosides
lamivudine
telbivudine
entecavir
nucleotides
tenofovir
adefovir
Tenofovir
nucleotide
first line tx for wild type HBV
used in pts with resistance to nucleosides
nephrotoxicity (PCT)
entecavir
guanosine nucleoside analog first line tx low rate of reistance doesn't cause renal impairment limited side effects
HCV standard of care
PEGylated IFNa + ribavirin
ribavirin
nucleoside analog of guanosine
inhibits RNA capping
potentiates action of PEGylated IFNa
contraindicated in pts with anemia or pregnant
Protease inhibitors (new agents)
simeprevir (2nd gen)
telaprevir (1st gen)
boceprevir (1st gen)
sofosbuvir (NS5B inhibitor)
RNA dependent RNA polymerase inhibitor
nucleotide analog
used for all HCV genotypes
NS5A inhibitors
NS5A protein important for viral replication and assembly of HCV
ledipasvir given in combo with PEGylated IFNa and ribavirin
elbasvir
velpatasvir
Genotype 1 HCV tx
ledipasvir +sofosbuvir
Genotype 1,2 and 3 HCV tx
velpatasvir +sofosbuvir
Elbasvir +grazoprevir
