GI- Antiviral For Hepatitis B And C Flashcards
Which patients can and cannot be given interferon alpha as a treatment
Only given in patients with well compensated livers, as noncompensated cirrhosis patients may lead to liver failure
What is the difference in pharmacokenetics between interferon alpha 2b and PEGylated interferon alpha 2a/2b
Regular interferon 2b has to be given daily
PEG has a longer half-life, more consistent blood levels, and slower clearance
What is the mechanism that administration of interferon alpha helps to clear a viral infection
- Infected cells will undergo lysosomes lysis
- Macrophages and NK cells are stimulated to clear infected cells
- Healthy cells upregulate antiviral properties.
What is the mechanism of action of interferon alpha
- Binds to JAk1 and tyrosine kinase 2 (TYK2)
- Activation of STAT
- Transcription of interferon stimulated genes
What are the proteins created by healthy cells as a result of transcription due to interferon alpha
- ZAP
- IFIT family
- OAS-RNAseL pathway
- PKR
What is the cause of the hepatitis “flare” as a result of interferon alpha administration
- HBV antigens decrease, and the ALT levels increase
- Caused by the interferon causing the lysis of the infected hepatocytes, so we see some liver damage, but also a decrease in the HBV levels
WHat are the contraindications and side effects of interferon administration
Contraindicated:pregnant or pts with cirrhosis
Side effects: Bone marrow suppression, neurotoxicity, flu like syndrome
What is the target for nucleoside and nucleotide based anti-hep drugs
DNA reverse transcriptase and DNA polymerase inhibitors
Can nucleosides and nucleotides be used in patients with cirrhosis
Yes
What is the mechanism of action for NRTI
Aka nucleoside/nucleotide reverse transcriptase inhibitors
-Inhibits the replication machinery of HBV and HCV
What is required for NRTIs to work properly
Kinase activities that convert the nucleosides into nucleotides
What is the group on nucleosides/tides that prevent the hepatitis virus from being able to replicate
The lack of OH groups
What are the nucleoside analogues used to treat HBV infection
- Lamivudine
- Telbivudine
- Entecavir
What are the nucleotide analogues used to treat HBV infection
Tenofovir
Adefovir
What is the mechanism of action for tenofovir
Adenosine nucleotide analog
What is the first line treatment for wild type HBV
Tenofovir
What patients can be administered tenofovir
Patients with resistance to lamivudine, telbivudine, or entecavir
*Due to resistance to tenofovir being rare
Which patients should avoid treatment with tenofovir
Those with kidney issues as is a strong proximal renal tubule nephrotoxin
What is the mechanism of action for entecavir
Guanosine nucleoside analog
What is the relation of resistance to entecavir
- Rare to be resistant in a naive patient
- Resistance to lamivudine gives about 50% resistance to entecavir
What is the better choice of drug for hepatitis B in those patients with renal insufficiency
Entecavir
What is the rate of resistance in lamivudine
Long term efficacy is not good due to the frequent mutation in the catalytic domain of HBV polymerase
What is the mutation in HBV polymerase that leads to decreased efficacy of long term treatment of lamivudine
YMDD to YVDD (methionine to valine)
In 2011, what was the standard of treatment for HCV that had some success
PEGylated interferon alpha + ribavirin
What is the mechanism of action for ribavirin
- Guanosine nucleotide that interferes with GTP production
- inhibits the capping of viral mRNA
- Inhibits viral RNA polymerase
- Upregulates interferon stimulated genes (ISGs)
What are the complication of ribavirin
- Anemia
- Pregnancy
What is the mechanism of action of telaprevir
First generation protease inhibitor at NS3 catalytic site
What is the mechanism of boceprevir
First generation protease inhibitor at NS3 catalytic site
What is the mechanism of action of simeprevir
Second generation protease inhibitor at catalytic site NS3
What is the mechanism of action of Sofobuvir
Nucleotide analog, NS5B inhibator, aka site NS5B in the RNA dependent RNA polymerase
Which genotypes of HCV are disrupted by sofosbuvir
All genotypes
What is the mechanism of action for ledipasvir
Inhibits NS5A
What is the mechanism of action for elbasvir
Inhibits NS5A
What is the mechanism of action for velpatasvir
Inhibits NS5A
Which hepatitis would the drug Ribavirin be given for
HCV
Which hepatitis would the drug simeprevir be given for
HCV
Which hepatitis would the drug telaprevir be given for
HCV
Which hepatitis would the drug boceprevir be given for
HCV
Which hepatitis would the drug grazoprevir be given for
HCV
Which hepatitis would the drugsofosbuvir be given for
HCV
Which hepatitis would the drug ledipasvir be given for
HCV
Which hepatitis would the drug elbasvir be given for
HCV
Which hepatitis would the drug velpatasvir be given for
HCV
