Antivirals - Hepatitis C

Question 1

2 agents for hepatitis C infections

Answer 1

Ribavirin

Interferons

Question 2

What type of analog is ribavirin?

Answer 2

Purine nucleoside analog

Question 3

Spectrum of activity of ribavirin

Answer 3

Inhibits replication of a wide range of DNA and RNA viruses

influenza A & B, parainfluenza, RSV, paramyxoviruses, HCV, HIV-1

Question 4

MOA of ribavirin

Answer 4

(not fully understood)

• interfere with synthesis of guanosine triphosphate
• inhibit capping of viral messenger RNA
• inhibit viral RNA-dependent polymerase

Question 5

What is the effect of high fat meals on the bioavailability of ribavirin?

Answer 5

Increase bioavailability

Question 6

What is the effect of antacids on the bioavailability of ribavirin?

Answer 6

Decrease bioavailability

Question 7

Excretion of ribavirin?

Answer 7

Renal

Question 8

Clinical uses of ribavirin

Answer 8

• chronic HCV infection
• severe bronchiolitis or pneumonia (children) - aerosol
• influenza virus, parainfluenza, adenovirus, vaccinia, measles - IV/aerosol

Question 9

Available dosage forms for ribavirin

Answer 9

IV

Aerosol

Question 10

ADRs of ribavirin

Answer 10

Hemolytic anemia

Depression, fatigue, irritability, rash, insomnia, nausea, pruritis

Question 11

Contraindications of ribavirin

Answer 11

anemia, ESRD, ischemic vascular disease, PREGNANCY

Question 12

Why is ribavirin contraindicated in pregnancy?

Answer 12

Because it is teratogenic and embryotoxic

Question 13

What agents are potent cytokines with antiviral, immunomodulatory, antiproliferative activities?

Answer 13

Interferons

Question 14

What are the three major classes of interferons?

Answer 14

Alpha, beta, gamma

Question 15

IFN-a and IFN-b are produced by ___ cells.

Answer 15

ALL CELLS

Question 16

IFN-gamma production is restricted to ______ and ___ cells.

Answer 16

T-lymphocytes and NK cells

Question 17

MOA of interferons

Answer 17

• inhibit transcription, translation, post-translational processing, virus maturation, virus release

Question 18

What is the effect of polyethylene glycol (PEG) on interferons?

Answer 18

• slows absorption
• decrease clearance
• higher and more prolonged serum concentrations

Question 19

What is PEGASYS?

Answer 19

Peginterferon alfa-2a

Question 20

What is PEGINTRON?

Answer 20

Peginterferon alfa-2b

Question 21

Mechanism of clearance of interferon alfa-2A?

Answer 21

via the LIVER

Question 22

Mechanism of clearance of interferon alfa-2B?

Answer 22

via the KIDNEYS

Question 23

Dose reduction is required for IFN-alfa 2a and IFN-alfa 2B in what patients?

Answer 23

ESRD patients

Question 24

ADRs of interferons

Answer 24

• Flu-like syndrome
• transient hepatic enzyme elevations
• mood disorders, depression, somnolence
• MYELOSUPPRESSION
• Fatigue, weight loss, rash
• pneumonitis, cardiotoxicity

Question 25

Interferons are contraindicated for?

Answer 25

• PREGNANCY
• hepatic decomposition
• autoimmune disease
• cardiac arrythmia
• psychiatric disease, epilepsy
• severe renal insufficiency
• thyroid disease
• ischemic cardiac disease

Question 26

What is the effect of interferons on theophylline and methadone levels?

Answer 26

Increase theophylline and methadone levels

Question 27

What ADR is observed when interferons are co-administered with didanosine?

Answer 27

hepatic failure

Question 28

What ADR is observed when interferons are co-administered with zidovudine?

Answer 28

cytopenia