C.6. Hepatitis drugs

Question 1

Nucleoside nucleotide analogues for hepatitis B

Answer 1

Lamivudin, emtricitabin
entecavir (guanosine analogue)
Telbivudin (thymidine analogue)
Adefovir (AMP analogue)
Tenofovir.

Taken orally

Ribavirin

Question 2

Interferons

Answer 2

Hepatitis B:
Peginterferons-alpha-2a injected subcutaneously
Interferon-Alpha-2b injected intramuscularly or subcutaneously

Question 3

prefered treatment for Hep C

Answer 3

The preferred treatment for chronic hepatitis C
is the combination of peginterferon-α-2a or peginterferon-α-2b plus ribavirin, which is more effective than the combination of standard interferons
and ribavirin.

For genotype 1 chronic hepatitis C virus (HCV), an NS3/4A
protease inhibitor (such as boceprevir or telaprevir) should be added to
pegylated interferon and ribavirin.

Question 4

Interferons:

Answer 4

glycoproteins that interfere with the viral infection of cells.
There are alpha beta and gamma types, where interferon alpha and interferon alpha-2b have been approved for the treatment of:
1) Hep B, C.
2) Condylomata acuminata
3) cancers such as hairy cell luekmia and kaposi sarcoma.

Interferons are usually pegylated (making the molecules much bigger) which delays absorption from the injection site allowing for it to last longer.

Mechanism: NOt completely understood (induction of host enzymes which inhibit the viral products).

Kinetics:
admin: subcutaneously, intravenously.

Adverse:
Flue like symptoms
GI disturbances
fatigue and mental depression which all subside with administration
dose limiting toxicities: bone marrow supression, 
weight loss
neruotoxocity
thyroiditis 
heart failure

Question 5

Lamivudine

Answer 5

cytosine analog, inhibits both Hep B and HIV reverse transcriptase.

Lamivudine must be phosphorylated by host cellular enzymes to the triphosphate form (active form) which inhibits the HBV RNA depedent DNA polymerase.

Kinetics:
Orally taken
excreted in urine unchanged.

Question 6

ADefovir

Answer 6

A nuclotide analog that is phosphorylated by cellular kinases to adefovir disphosphate which is then incorporated into viral DNA.

Kinetics:
Glomuerlar tubular filration and secretion

adverse:
Discontinuation can exacberate the hepatitis
nephrotoxicity in chronic use.
should not be used with tenofovir.

Question 7

entecavir

Answer 7

guanosine nucloside analogue for HBV
undergoes phosphorylation to the triphosphate form which competes for natural substrate (Deoxy guanosine triphosphate) for viral RT.

Question 8

telbivudine

Answer 8

thymidine analog that can be used for HBV.
intraceullar phosphorylation which terminates the DNA elongation chain.

Orally taken
Eliminated in kindey unchanged

Question 9

boceprevir and telaprevir

Answer 9

orally taken, adjunctive treatment of chronic HCV genotype 1.
They are HCV NS3/4A serine protease inhibitors covalently and reversibly to the NS3 protease active site, thus inhibiting the viral replication; however resistance develops quickly.

This is why we use it with peginterferons.

Can cause
Anorectal discomfort and rash and anemia