Hepatitis Drugs Flashcards
Goals for hepatitis B treatment
- virus will not be fully eradicated and relapse is possible even if therapy is successful
- goal is to slow cirrhosis and hepatocellular carcinoma development
MOA interferons
- activate JAK1 and TYK2
- phosphorylated receptor leads to activation of STAT 1/2
- these go to the nucleus and transcribe interferon stimulated genes
- these inhibit viral protein synthesis
Indications for interferons
used in well compensated liver disease, don’t want long term treatment (may be want to get pregnant in 2-3 years)
interferon with short half life (+frequency of administration)
interferon alpha-2b (must be given every 36 hours)
interferons with longer half life
1) PEGylated interferon α-2b
2) PEGylated interferon α-2a
adverse effects of interferons
80% of patients have flu-like syndromes, bone marrow suppression, and neurotoxicity. Improve with continued therapy
Initial reaction to interferons
leads to a flare of hepatitis (good sign)
Contraindications interferons
- dangerous in decompensated cirrhosis (flare will make liver disease much worse)
- don’t use with patients wanting to be pregnant soon
nucleoside drugs (3)
- Lamivudine
- telbivudine
- Entecavir
Nucleotide drugs (2)
- Tenofivir
- Adefovir
MOA Nucleoside and Nucleotides
incorportated into viral DNA to block transcription of hepatitis B virus (HBV DNA reverse transciptase/DNA polymerase inhibitors)
First line nucleoside/nucleotide for HBV infection
Entecavir (guanosine analog)
First line nucleoside/nucleotide for HBV infection if resistant to nucleosides
Tenofovir
Suffix Nucleotides
-fovir
Adverse effects tenofovir
nephrotoxicity (proximal renal tubule)
Highlights nucleoside/nucleotide drugs (3)
- oral agents that suppress HBV
- better tolerated and higher response rate than interferon Tx
- can be used in patients with decompensated cirrhosis
What HBV drug (nucleoside/nucleotide) is better for renal insufficiency patients?
nucleosides (entecavir)
Factors influencing selection for nucleotide/sides for HBV treatment
- resistance profile
- efficacy (clearance of HBV DNA)
- usefulness with HIV co-infection
Do therapies for HBV fully eradicate the virus?
NO, relapse is always possible, even with therapy
nucleoside for HCV used in concert with PEG interferons to potentiate their action
Ribavirin (guanosine analog)
Suffix NS3/4A inhibitors
-previr
Suffix NS5B inhibitors
-buvir
Suffix NS5A inhibitors
-asvir
Treatment for patients with both HBV and HCV
treatment directed at predominant virus
Contraindications Ribavirin
anemia and pregnancy (specific regimen listed out months tests and 2 forms of birth control)
MOA grazoprevir, paritaprevir, simeprevir
inhibit NS3/4A serine protease
Adverse interactions paritaprevir
CYP3A, drug-drug interaction
Special instructions for Simeprevir use
must be taken with food to maximize absorption
MOA dasabuvir, sofobuvir
inhibit NS5B RNA polymerase (polymerase is highly conserved so it is effective against all 6 HCV genotypes)
interactions dasabuvir
CYP3A, drug-drug interactions
Interactions elbasvir, ombitasvir
CYP3A
First once-daily single-tablet regimen with pangenotypic activity
Velpatasvir + sofosbuvir
nucleoside vs nucleotide
nucleoside: -OH group
nucleotide: phosphate group
Can HCV be cured?
Yes, because it is RNA and not incorporated into the host DNA
