[PHARM] Viral Hepatitis Pharmacology Flashcards
What is the goal for treatment of HBV?
Slow the development of liver disease
Can prevent from progressing to hepatocellular carcinoma
Define:
Chronic active hepatitis
Acute hepatitis state that continues without normal recovery (longer than 6-12 months)
What do interferons do within the body?
Interferons are host cytokines that exert complex
antiviral, immunomodulatory and antiproliferative actions
What are the (technically 3) types of interferons used to treat hepatitis?
Inferferon alpha-2b
PEGylated interferon alpha-2b
PEGylated interferon alpha-2a
*The PEGylated interferons are basically the same for our purposes
When would you give an interferon drug?
Treatment of patients with well compensated liver disease
You should NOT give interferons if your patient….
Is planning to be pregnant within 2-3 years
***DANGEROUS to give to patients in decompensated cirrhosis
What are the differnces in duration of action of inferferon alpha 2-b VERSUS PEGylated interferons alpha2a/2b?
Inferferon alpha 2b doesn’t last as long as PEGylated interferons
What are the 3 primary functions of interferons in surrmounting an immune response?
- Protect nearby healthy cells
- Signal macrophages and NK cells to clear infection
- Lysosome lysis, lysis of infected cell
What is the MOA of interferon alpha?
Interferon alpha binds to JAK1 and TYK2 which activates them
This causes STAT1 and STAT2 to become active (phosphorylated) and induce the activation of transciption of interferon stimulated genes (ISGs)
What are the adverse effects that occur with interferon alpha/PEGylated interferons?
80-90% of patients experience SOME kind of adverse effect
FLU LIKE SYNDROME
Fatigue and mental depression
What are the dose limiting toxicities associated with interferon alpha/PEGylated interferon?
Bone marrow suppression
Neurotoxicity-behavioral changes
What is the MOA of nucleosides/nucleotides treatment for HBV?
HBV DNA reverse transciptase/DNA polymerase inhibitors
How do you take nucleosides/nucleotides for treatment of HBV?
ORALLY
*much easier to take than the interferon drugs
What drugs would you use for a patient that has decompensated cirrhosis?
Nucleoside/nucleotides
What are the (3) nucleoSIDE drugs?
Lamivudine
Telbivudine
Entecavir
What is are the two nucleoTIDE drugs?
Tenofovir
Adefovir
Which one has the monophosphate attached?
Nucleosides?
Nucleotides?
NucleoTIDES!!! have the monophosphate group
What is the first line treatment for wild-type HBV?
Tenofovir
What is the unique AE of tenofovir?
Nephrotoxicity
What category drug is tenofovir in?
Nucleotide analog of adenosine
What is the first line treatment of HBV in patients that have renal insufficiency?
Entecavir
What are the TAKE HOME MESSAGES for HBV treatment?
- Therapies for HBV fail to fully eradicate the virus
- RELAPSE of hepatitis induced by HBV is always possible
What are the interferon drugs?
Interferon alpha2b
PEGylated interferon alpha 2b
PEGylated interferon alpha 2a
What category is lamivudine in?
Nucleoside
What category is telbivudine in?
Nucleoside
What category is entecavir in?
Nucleoside
What category is tenofovir in?
Nucleotide
What cateogory is adefovir in?
Nucleotide
Which can be cured?
HBV or HCV?
HCV
*remember: HCV has a C in it, so it can be CURED
What is the primary drug used for HCV (historically)?
Ribavirin
What are the 3 things that ribavirin does therapeutically?
- Interferes with synthesis of GTP
- Inhibits capping of viral mRNA
- Inhibits the viral RNA dependent polymerase
Contraindications for ribavirin?
Anemia
Pregnancy
What do the NEW treatments for HCV infection primarily target?
Translation and Processing
What are the (3) NS 3/4A protease inhibitors?
Grazoprevir
Paritaprevir
Simeprevir
Which drug within the NS 3/4Aprotease inhibitors has CYP34a drug interactions and has the AE of nausea, pruritis and insomnia?
Paritaprevir
Which of the three NS 3/4A protease inhibitors needs to be taken with food?
Simeprevir
What are the two drugs that are NS5B RNA polymerase inhibitors?
Dasabuvir
Sofosbuvir
Which NS5B RNA polymerase inhibitor is a prodrug?
Sofosbuvir
Which NS5B RNA polymerase inhibitor has drug-drug interactions with CYP3A and AE of nausea, pruritus and insomia?
Dasabuvir
What are the 4 NS5A inhibitors?
Elbasvir
Ledipasvir
Ombitasvir
Velpatasvir
What is the common ending for NS3/4A inhibitors?
-Previr
Grazoprevir
Paritaprevir
Simeprevir
What is the common ending for NS5B inhibitors?
Dasabuvir
Sofosbuvir
*REMEMBER, if you are treating NS5B, you add a B in front
What is the common ending for NS5A inhibitors?
-asvir
Elbasvir
Ledipasvir
Ombitasvir
Velpatasvir
*REMEMBER, if you are treating NS5A, remember to have an A
