Pharmacology: Drugs for Hepatitis Flashcards
What are people who have HBV at risk for?
HCC
hepatocellular carcinoma
Interferon alpha class
- used for patients with well compensated liver disease
- who do not wish to be on long term treatment or are planning to be preggo
PEG interferones
1x a week as opposed to 3x which is nice
MOA of Interferons
changes transcription of UNINFECTED CELLs only
- Tyk2 and JAK1 receptors
- binds, kinases activated, autophosphorylation, attracts STATs
- TF goes to nucleus
- ISG’s are made from DNA
Products of ISG?
2’5’ OAS… degrades viral RNA
PKR… inhibits protein synthesis
Which T cell phenotype does IFN’s favor?
TH1
- increased inflammation… kills infected liver cells too
- remember that IL-12 makes TH1 cells
what are IFN’s dangerousin?
decompensated cirrhosis
-remember that we will damage some liver in the process
What drug class can be used regardless of liver status?
nucleosides!
- they just stop transcription or something…. competitive inhibitors… inserted into DNA and then the cell dies
- just like with HIV
Name the nucleosides
Lamivudine
Telbivudine
Entecavir
Tenofivir (already a monophosphate)… remember that the host cell does that first phosphorylation… main route of resistance
First line oral anti-HBV agents
Tenofivir and entecavir
What is an adverse event of tenofivir?
Nephrotoxicity
-proximal renal tubule may be particularly susceptible
Which drug has a lot of HBV resistant to it?
Lamivudine
-so, it’s not a first line agent
What do we add to IFN to treat HCV?
ribavirin
MOA of ribavirin?
gets P’ed
- mono P stops IMP dehydrogenase… no purine synthesis
- Tri P stops TNA-dependent RNA polymerase…
- potentiates IFN action… alters Th1 balance as well
How does the body get rid of Ribavirin
- hepatic metabolism
- gets avidly taken up by RBCs
- stays in there for 40 days
