Waller Pharm CIS

Question 1

Agents for Hepatitis B Virus (HBV)

Answer 1

Nucleoside/Nucleotide Analogs (NAs): 
Adefovir 
! Entecavir*
Lamivudine* (3TC)
Telbivudine
! Tenofovir*
       * anti-HIV activity

! Peginterferon alfa

Question 2

Agents for Hepatitis C Virus (HCV)

Answer 2

Direct-Acting Antivirals (DAAs):
! Daclatasvir (Daklinza) 
! Ledipasvir-sofosbuvir (Harvoni)
! Ombitasvir-paritaprevir-ritonavir plus dasabuvir (Viekira Pak)
! Simeprevir (Olysio) 
! Sofosbuvir (Sovaldi) 

Peginterferon alfa

Protease Inhibitors (PIs)

• • Boceprevir (Victrelis)
• • Telaprevir (Incivek)

! Ribavirin

Question 3

Viral serology testing

Answer 3

Suspect acute viral hepatitis
Obtain LFTs
Elevations in serum aminotransferases? AST and ALT

Determine cause: viral serologic tests
- IgM antibody to HAV
HBsAg
IgM antibody to hepatitis B core (IgM anti-HBc)
Antibody to HCV (anti-HCV)

Question 4

HBeAg seroconversion

Answer 4

development of antibodies

indicates lower levels of HBV; good predictor of viral clearance

Question 5

treatment goals for HBV include

Answer 5

HBeAg seroconversion
Prevention of complications of viral hepatitis (cirrhosis, HCC, hepatic failure)
Suppress viral replication (has been associated with normalization of serum ALT, loss of HBeAg with or without detection of anti-HBe, and improvement in liver histology)

No viral cure for B. Hep C does, however, have a cure possibility

Question 6

decompensated cirrhosis

Answer 6

symptoms of cirrhosis:

encephalopathies, ascites, coagulopathies, jaundice, etc.

Question 7

HBV disease course

Answer 7

HBV has a fluctuating disease course. One high HBV DNA level is a poor predictor of prognosis – must have regular disease monitoring to determine need for antiviral therapy.

Question 8

treatment options for pt with chronic Hep B (6 months)

Answer 8

Peginterferon and the nucleoside/ nucleotide analogs (adefovir, entecavir, lamivudine, telbivudine, telbivudine, tenofovir)

Question 9

2 agents only used for Hep C

Answer 9

Ribavirin, sofosbuvir

Question 10

How does entecavir work?

Answer 10

NA; inhibits DNA polymerase

Question 11

Ribavirin works how?

Answer 11

inhibits RNA polymerase

Question 12

Sofosbuvir works how?

Answer 12

Inhibits NS5B dependent RNA polymerase

Question 13

Tenofovir works how?

Answer 13

NA; inhibits DNA polymerase

Question 14

advantages of peginterferon compared to interferon?

Answer 14

given subcutaneously, slower clearance with complexed polyethylene glycol, less frequent dosing, higher SVR rate

can give once weekly

Question 15

advantages of peginterferon compared to nucleoside (-tide) analogs?

Answer 15

finite duration of treatment, resistance not a problem, more durable responses.

analogs can be very long-term treatment.

Question 16

agent preferred ifi pt has decompensated (hep B) liver disease?

Answer 16

nucleotide or -side analogs;

peginterferon is contraindicated

Question 17

pegintereron contraindications

Answer 17

psych issues
autoimmunity
decompensated liver disease

Question 18

Which NAs are preferred for first-line treatment of HBV?

Answer 18

Entecavir and Tenofovir

lower potential for resistance and better treatment response

Question 19

drawbacks to adefovir

Answer 19

slow response, low likelihood of seroconversion

Question 20

drawbacks of lamivudine

Answer 20

high rate of resistance

Question 21

drawbacks of telbivudine

Answer 21

high rate of resistance

Question 22

What is an SVR?

Answer 22

sustained virologic response

absence of HCV RNA by PCR 3 months after completion of therapy

associated with improved liver histology, decreased HCC, sometimes cirrhosis regression

Question 23

Which of the following does not have activity against HCV?
Dasabuvir
Ombitasvir
Paritaprevir
Ribavirin
Ritonavir

Answer 23

Ritonavir; we’re using it for it’s CYP 3A inhibitory activity; increases plasma concentrations of paritaprevir and overall drug exposure

Question 24

Direct-Acting Antivirals: NS5A

Answer 24

Involved in organization of replication complex, regulating replication, viral particle assembly

Daclatasvir
Elbasvir
Ledipasvir
Ombitasvir
Velpatasvir

Question 25

Direct-Acting Antivirals: NS5B

Answer 25

RNA-dependent RNA polymerase necessary for viral replication

Dasabuvir
Sofosbuvir

Question 26

Direct-Acting Antivirals: NS3/4A protease

Answer 26

Grazoprevir
Paritaprevir
Simeprevir

Question 27

daclatasvir, how does it work

Answer 27

–> NS5A

Question 28

peginterferon, how does it work

Answer 28

–> viral penetration, translation, and viral maturation

Question 29

ribavirin, how does it work

Answer 29

-> inhibits initiation/ elongation of RNA

Question 30

ritonavir, how does it work

Answer 30

–> inhibits CYP3A, used for “boosting” properties

Question 31

ribavirin drawbacks

Answer 31

chance of hemolytic anemia

Question 32

peginterferon drawbacks

Answer 32

flu-like symptoms

Question 33

chronic HBV infection, best course of action?

Answer 33

tenofovir

Lamivudine is not first-line due to high rate of drug resistance.

Ribavirin is not indicated in HBV

Question 34

chronic HBV, Resistance testing reveals the presence of a drug mutation.

The drug most appropriate for treatment, inhibits viral:

Answer 34

DNA polymerase

This question is asking for the mechanism of action of tenofovir. Tenofovir is a nucleotide analog which competitively inhibits DNA polymerase, incorporates into viral DNA, and causes chain termination.

Question 35

agent which allosterically inhibits NS5B RNA-dependent RNA polymerase.

Which of the following was most likely prescribed?
A
daclatasvir.
B
dasabuvir.
C
peginterferon.
D
sofosbuvir.
E
tenofovir.

Answer 35

Correct Answer:
dasabuvir.
Explanation:
Daclatasvir (Choice A, incorrect) binds NS5A inhibiting viral RNA replication and virion assembly.  Peginterferon (Choice C, incorrect) exerts complex antiviral, immunomodulatory, and anti-proliferative actions but is not linked to the HCV non-structural (NS) proteins.  Sofosbuvir (Choice D, incorrect) inhibits NS5B RNA-dependent RNA polymerase but does so through competition with nucleotides resulting in chain termination vs. allosteric inhibition.  Tenofovir (Choice E, incorrect) is a nucleotide analog which inhibits DNA polymerase.  This leaves dasabuvir (Choice B, correct), as the most appropriate answer, which through allosteric modification of NS5B interferes with viral replication.
OK

Question 36

Why has ritonavir been added to this regimen?
A
Alleviates adverse effects of the HCV regimen
B
Covers HBV in an at-risk patient
C
Inhibits CYP3A enhancing overall drug exposure
D
Provides HIV coverage in an at-risk patient
E
Targets HCV by inhibiting viral protease

Answer 36

Inhibits CYP3A enhancing overall drug exposure
Explanation:
Ritonavir does not have activity against HBV, HCV, or HIV. It is used solely for its potent CYP3A inhibitory effects (“boosting” properties) which increase plasma concentrations of paritaprevir (and other viral protease inhibitors) to increase overall drug exposure.