Viral Hepatitis Pharm - Sheehy Flashcards
(31 cards)
what is primarily used for treatment of patients with well compensated liver disease
interferon alpha
cons:
- dangerous in decompensated cirrhosis
- parenteral administration
- side effects in 80% of pt (flu like sx)
interferons for HBV
which has a longer half life, PEGylated interferon 2a/2b, or interferon a2b
PEGylated
- lasts much longer, so less doses needed
what drug acts in an autocrine fashion, stimulating lysosome lysis?
- also signal nearby macrophages and NK cells to clear infected cell
interferons
what is seen as a sign that seroconversion of interferon a is progressing?
a hepatitis “flare”
- dangerous in decompensated cirrhosis because the spike would make the cirrhosis worse, more prone to infections
HBV DNA reverse transcriptase inhibitor (NRTI)
- oral agents that are used to suppress HBV infection
- better tolerated and higher response rate than interferon a
- can be used in pts with decompensated cirrhosis
nucleosides
what is the active antiviral agent of NRTI’s?
nucleotide triphosphate (converted by cellular kinases)
what nucleoside lacks a 3’-OH, and has a 3’ sulfur that prevents the addition of any more nucleotides?
lamivudine
lamivudine
telbivudine
entecavir
nucleosides
tenofovir
adefovir
nucleotides
- have a monophosphate
what causes nucleoside resistance?
slow or low conversion of nucleosides into a nucleotide monophosphate allows resistance
nucleotide analog of adenosine
- first line tx for wild-type HBV
- used in pts with nucleoside resistance
- nephrotoxicity (proximal renal tubule)
tenofovir
what drug is a better choice for pts with renal insufficiency?
entecavir
- is well tolerated, limited side effects
what does a YMDD -> YVDD mutant in catalytic domain of HBV polymerase lead to?
subsequent virological breakthrough
- long term efficacy of lamivudine limited by drug resistance
RNA virus that is NOT incorporated into the host DNA
HCV
what is the tx of HCV?
PEGylated interferon a + ribavirin
- 24-48 week regimen
- less than 50% cure rate overall
this drug interferes with synthesis of GTP
- inhibits capping of viral messenger RNA
- inhibits viral RNA-dependent polymerase of certain viruses
- potentiates the action of PEGylated interferon 2a and 2b
ribavirin
- nucleoside analong of guanosine
what are the contraindications of ribavirin?
anemia, PREGNANCY (have to take a test every month to make sure they aren’t!)
this drug class inhibits the NS3/4A serine protease, which inhibits HCV post-translational processing and replication
nonstructural protein (NS) 3/4A protease inhibitors
- grazoprevir
- paritaprevir
- simeprevir
which NS3/4A causes fatigue, headache and nausea?
grazoprevir
which NS3/4A
- causes pruritis and insomnia
- is a CYP34A inhibitor -> drug-drug reactions
- is used in combination with ritonavir
paritaprevir
which NS3/4A must be take with food to maximize absorption and is generally well tolerated?
simeprevir
what HCV drug class is highly conserved, having efficacy against all 6 genotypes of HCV?
NS5B RNA polymerase inhibitors
- dasabuvir
- sofosbuvir
non-nucleoside NS5B allosteric inhibitor
- drug-drug interations, CYP34A
- most common adverse effects include nausea, pruritis, insomnia
dasabuvir
