Flashcards in Viral Hepatitis Pharm - Sheehy Deck (31)
what is primarily used for treatment of patients with well compensated liver disease
cons of interferons for HBV
- **dangerous in decompensated cirrhosis**
- parenteral administration
- side effects in 80% of pt (flu like sx)
which has a longer half life, PEGylated interferon 2a/2b, or interferon a2b
- 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
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
better than whaat?
Can be used with
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**
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?
name the nucleosides
name the nucleotides
how are they different chemically?
- 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)**
what drug is a better choice for pts with renal insufficiency?
- 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
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**
- 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
which NS3/4A causes fatigue, headache and nausea?
- causes pruritis and insomnia
- is a CYP34A inhibitor -> drug-drug reactions
- is used in combination with ritonavir
which NS3/4A must be take with food to maximize absorption and is generally well tolerated?
what HCV drug class is highly conserved, having efficacy against all 6 genotypes of HCV?
NS5B RNA polymerase inhibitors
non-nucleoside NS5B allosteric inhibitor
- drug-drug interations, CYP34A
- most common adverse effects include nausea, pruritis, insomnia
NS5B nucleotide analog, prodrug
- generally well tolerated
which NS5A inhibitor is used in combination with grazoprevir, and has adverse effects of fatigue, headache, nausea?
which NS5A inhibitor is used in combination with sofosbuvir, and has adverse side effects of fatigue, headache, and asthenia (weakness)?
which NS5A inhibitors are metabolized by CYP34A?
paritaprevir, ritonavir, dasabuvir
which drug mentioned is used as a "boosting agent", helping other drugs to do their job better?