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
MOA of sofosbuvir?
Targets NS5B-RNA polymerase prodrug
* Carrier linked bioprecursor
* False substrate for RNA polymerase
Indication for sofosbuvir?
- Combo with ribavirin for HCV 2-3
- Curative in some cases
What are your NS5A inhibitors?
Ledipasvir
Velpatasvir
Pibrentasvir
What is the MOA of NS5A inhibitors?
Zinc binding enzyme at allosteric site
How is sofosbuvir metabolized?
To uridine triphosphate mimic -> incorporated into RNA by NS5B polymerase
Ledipasvir/Sofosbuvir
Harvoni
Velpatasvir/Sofosbuvir
Epclusa
Pibrentasvir/Glecaprevir
Mavyret
MOA of glecaprevir?
NS3/4A protease inhibitor -> new viral particles can’t fully develop/mature
* Does not trap
* Cyclic peptide mimic
