Antiviral 1 - Hepatitis

Question 1

Differences between HBV and HCV?

Answer 1

Hep B: DNA virus, does integrate into host genome, vaccination is available

Hep C: RNA virus, cannot integrate into host genome, leading indication for liver transplantation/kills more than Hep B, and no vaccine available (heterogeneity hinders the development of vaccines)

Question 2

Pegylated Interferon 2-alpha, Recombinant Interferon Alpha: Indications?

Answer 2

Hepatitis B, papillomavirus

Hep C no longer a recommended treatment

Question 3

Pegylated Interferon 2-alpha, Recombinant Interferon Alpha: How do they work?

Answer 3

They are antiproliferative and have immune modulating actions, increase phagocytes

Question 4

Pegylated Interferon 2-alpha, Recombinant Interferon Alpha: Dosing?

Answer 4

Given SubQ 3 times a week for 48 weeks

Cray

Question 5

Pegylated Interferon 2-alpha, Recombinant Interferon Alpha: Adverse effects?

Answer 5

Fever, chills, flu-like syndrome
Hypotension, chest pain, arrhythmias
GI disturbances
Leukopenia, thrombocytopenia

Question 6

Pegylated Interferon 2-alpha, Recombinant Interferon Alpha: Cautions?

Answer 6

Caution in pulmonary disease, diabetes, coagulation disorders
Causes mood disorders - do not use in untreated or severe depression
Contraindicated in pregnancy

Question 7

Which Hep B treatment is contraindicated in pregnancy?

Answer 7

Interferon 2 Alphas

Question 8

Lamivudine: What is it?

Answer 8

Cytosine nucleoside

Inhibits DNA polymerase/reverse transcriptase in HBV

Question 9

Lamivudine: Indications

Answer 9

Used in HBV in adults and children, usually treat for 1 year (doesn’t cure HBV!!)

Question 10

Lamivudine: Clinical effects

Answer 10

Normalizes liver enzymes ~40%
Reduces hepatic inflammation ~50%
Renal elimination
Risk of lactic acidosis

Question 11

Telbivudine: What is it?

Answer 11

Thymidine analog

Inhibits DNA polymerase/reverse transcriptase in HBV

Question 12

Telbivudine: Cautions

Answer 12

Renal elimination

Increased risk of lactic acidosis

Question 13

Telbivudine: Adverse effects

Answer 13

Myopathy

Peripheral neuropathy

Question 14

Tenofovir, Adefovir: What are they

Answer 14

Adenosine analogs

Inhibit viral DNA polymerase and reverse transcriptase

Question 15

Tenofovir, Adefovir: Indications

Answer 15

Hep B and Lamivudine resistant HBV

Also effective in HIV

Question 16

Tenofovir, Adefovir: Duration

Answer 16

Long term treatment, doesn’t cure infection

Question 17

Tenofovir, Adefovir: Adverse effects

Answer 17

Both cause nephrotoxicity

Tenofovir can also cause decreases in bone density

Headache, abdominal discomfort, and diarrhea at low doses

Question 18

Entecavir: What is it

Answer 18

Guanosine nucleoside analog inhibits viral DNA polymerase and reverse transcriptase

REQUIRES INTRACELLULAR PHOSPHORYLATION

Question 19

Entecavir: Counseling points

Answer 19

Take on empty stomach

Question 20

Entecavir: Cautions

Answer 20

Renal elimination

Question 21

Entecavir: Compared to other drugs

Answer 21

It is superior to lamivudine in reducing viral load

Also has limited resistance development

Question 22

Describe the Hep C virus

Answer 22

Small, enveloped, single-stranded, positive sense RNA virus

Blood to blood contact (sharing needles, etc)

Seven major genotypes known as 1-7, divided into several subtypes with the number of subtypes depending on the genotype

Question 23

Hep C virus genotypes

Answer 23

70% in US caused by Genotype 1
20% type 2
1% by each of the other ones

Genotype 1 is also the most common in South America and Europe

Question 24

How many Hep C viruses are produced each day in an infected person?

Answer 24

1x10^12

Question 25

Recommended therapies for Hep C 1a?

Answer 25

Lepidasivir and Sofosbuvir: Paritavir/Ritonavir/Ombitasivir PLUS Dasabuvir and Ribaviron Sofosbuvir and Simeprevir

Question 26

Recommended therapies for Hep C 1b?

Answer 26

Lepipasivir and Sofosbuvir: Paritavir/Ritonavir/Ombitasvir plus Dasabuvir and Ribaviron Sofosbuvir and Simeprevir

Question 27

Recommended therapies for Hep C 2?

Answer 27

Sofosbuvir and Ribaviron

Question 28

Recommended therapies for Hep C 3?

Answer 28

Sofosbuvir and Ribaviron

Question 29

Recommended therapies for Hep C 4?

Answer 29

Ledipasivir and Sofosbuvir: Paritavir/Ritonavir/Ombitasvir plus Dasabuvir and Ribaviron Sofosbuvir and Simeprevir

Question 30

Recommended therapies for Hep C 5?

Answer 30

Sofosbuvir and Ribaviron

Question 31

Recommended therapies for Hep C 6?

Answer 31

Ledipasivir and Sofosbuvir

Question 32

Ledipasvir: What is it

Answer 32

NS5A inhibitor, alters posttranslational processing of HVC proteins

Question 33

Sofosbuvir: What is it

Answer 33

NS5B polymerase inhibitor, mimics uridine, blocks RNA elongation

Question 34

Ledipasvir, Sofosbuvir: How supplied

Answer 34

Fixed dose combination Harvoni

Question 35

Ledipasvir, Sofosbuvir: Adverse effects

Answer 35

Fatigue, headache

Question 36

Ledipasvir, Sofosbuvir: Drug interactions

Answer 36

Drug interactions with P-glycoprotein inducers (St johns wart, rifampin) Avoid concomitant use

Question 37

Ledipasvir, Sofosbuvir: Cost

Answer 37

12 week treatment is 95,000 | 24 week treatment is 189,000 (with cirrhosis)

Question 38

Which drug should not be taken with Amiodarone?

Answer 38

Sofosbuvir - March 2015 FDA warning about severe bradycardia caused when given these drugs to patients taking amiodarone (also worry about beta blockers)

Question 39

Ledipasvir, Sofosbuvir: Monitoring

Answer 39

Monitor pt in hospital first 48 hours CV function, monitor at home daily for 2 weeks

Question 40

Paritaprevir: What is it?

Answer 40

HCV NS3/4a protease inhibitor necessary for mature virus

Question 41

Ombitasvir: What is it?

Answer 41

HCV NS5A inhibitor, used for viral replication and virus assembly

Question 42

Dasabuvir: What is it?

Answer 42

Non-nucleoside inhibitor of RNA NS5B polymerase

Question 43

Ritonavir: What is it?

Answer 43

Potent CYP3A4 inhibitor, prevents metabolism of Paritaprevir

Question 44

Adverse effects of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir combo?

Answer 44

Fatigue, insomnia, pruritus Avoid in pregnancy and breast feeding!

Question 45

Simepravir: What is it?

Answer 45

2nd generation NS4/4A protease inhibitor, used in genotype 1, 2, 4 Hep C Inhibits posttranslational processing of HVC proteins

Question 46

Simepravir: How administered?

Answer 46

As combo with Ribavirin and Sofosbuvir

Question 47

Simepravir: Cautions?

Answer 47

CYP3A4 interactions, less drug interactions and none with birth control yay Avoid in pregnancy Increased liver enzymes

Question 48

Simepravir: Adverse effects?

Answer 48

Rash, photosensitivity, elevated bilirubin, myalgia, dyspnea, increased liver enzymes