Hepatitis (MC) - Block 3 Flashcards
What the types of HAV vaccines? Components?
Havrix and Vaqata: both contain inactivated virus
What are types of HBV vaccines? Components?
Engerix, Recombivax HB: Envelope proteins and HBsAg
What are the functions of IFN therapy?
Interfere with viral replication within host cell:
* Triggers host defence
* Induction of apoptosis in infected cells
What is pegylation?
Covalent modification of polyethylene glycol chains
Types of pegylated interferon?
IFN-a-2b: Pegintron
IFN-a-2a: Pegasys
How do IFN come in pegylated formulations?
- Reduces immunogenicity by masking agent from host immune system
- Protection from proteolytic degradation
- Increases solubility of hydrophobic molecules
- Increases hydrodynamic size -> prolonging circulation time and preventing renal clearance
- Improves PK -> QW instead of 3 weekly injections
ADR of pegylated IFN? CI?
- Flu
- Depression
- SZ
CI: renal insufficiency
What is polymerases?
Catalyze the polymerization during transcription replication process
* HBV has reverse transcriptase
Examples of Polymerase inhibitor?
Lamivudine (Epivir)
MOA of lamivudine?
L-confirmation HBV polymerase (reverse transcriptase) inhibitor:
* Prodrug must be phosphorylated (triphosphate) to become active
* Competes with deoxycytidine triphosphate for incorporation into viral DNA
* Competitive inhibitor of HBV polymerase for chain termination
Resistance emerges rapidly
MOA of adefovir dipivoxil?
Guanine analogue (prodrug):
* Acyclic nucleoside
Advantages of adefovir over lamivudine?
Resistance is slower to develop
MOA of entecavir?
Carbocyclic analogue of guanine that selectively inhibits HBV:
* Methylene group that bind to methionine on active site
Structure of Telbivudine?
L-isomer of thymidine: more effective than Lamivudine or Adefovir
What is the produg and salt form of tenofovir?
Prodrug: Tenofovir Disoproxil
Salt: Tenofovir Disoproxil Fumarate (TDF)
What is the BBW for anti-HBV therapies
Abrupt DC can cause acute exacerbations of HBV dx and hepatic dysfunction
What are the tx for HBV?
Pegylated IFN: Pefintron and Pegasys
Polymerase Inhibitor: Lamivudine, Adefovir, Entecavir, Telbivudine, Tenofovir
Tx for Hep C?
- Pegintron, Pegasys, non-peg IFN-a-2a and 2b
- Ribavirin
- Telaprevir
- Sofosbuvir
- Glecaprevir
- Ledipasvir
- Velpatasvir
- Pibrentasvir
Structure of ribavirin?
Mimics guanosine (not an analogue because it isn’t an actual base)
MOA of ribavirin?
- Inhibits of certain viral RNA-dependent RNA polymerase
- Inhibits cellular IMP dehydrogenase (IMP)
Due to ribavirin’s broad activity, what is a possible ADR associated with the drug?
Teratogenicity
MOA of Telaprevir? Indications?
Protease (serine) inhibitors
* Diketo group acts as a trap for serine at the active site (transition state) on the protease
Indication: approved against genotype 1 of HCV
Describe the activity of Ribavirin?
Broad activity against DNA and RNA viruses
