Viral Hepatitis Pharm

Question 1

Interferons Pharmacokinetics

Interferon-alpha 2B (1) vs PEGylated Interferon-alpha (4)

Answer 1

Interferon-alpha 2B taken daily

PEGylated Interferon-alpha 2A/2B:
Has longer half-life, slower clearance and steadier concentration
Can be administered once a week

Question 2

Interferons for HBV

Pros (4) and Cons (3)

Answer 2

Pros:
Shorter treatment course
Good efficacy
Resistance is rare
Reduces HBV DNA and HBeAg

Cons:
Dangerous in decompensated cirrhosis
Flu-like syndrome side effects in most people
Dose limiting bone marrow and neuro toxicities

Question 3

Interferons Mechanism of Action (5)

Answer 3

Binds Type 1 IFN receptor to activate JAK1/TYK2

JAK1/TYK2 phosphorylate intracellular IFN receptor

STAT1/STAT2 are recruited and dimerized

STAT dimer acts as transcription factor for Interferon Stimulated Genes (ISGs)

ISGs inhibit viral replication, protein synthesis and translation

Question 4

Nucleosides/Nucleotides
Mechanisms of Action (3)
Mechanisms of Resistance (2)

Answer 4

Inhibit reverse transcriptase
Inhibit DNA polymerase
Require nucleotide triphosphate conversion by cellular kinases to be active

Impaired purine/pyrimidine kinase activity slows conversion to nucleotide monophosphate
Mutation of DNA polymerase blocking binding

Question 5

Examples of NRTI’s

Nucleosides (3) and Nucleotides (2)

Answer 5

Nucleosides:
Lamivudine
Telbivudine
Entecavir

Nucleotides:
Tenofovir
Adefovir

Question 6

Tenofovir

Drug Class, Use and Adverse Effect

Answer 6

Nucleotide adenosine analog

Used in nucleoside resistance
(Tenofovir resistance is rare)

Nephrotoxic
(Adefovir is also nephrotoxic)

Question 7

Entecavir

Drug Class, Uses (2) and Resistance Profile (2)

Answer 7

Nucleoside guanosine analog

First line HBV agent
Use in renal failure patients

Resistance rare in naive patients
50% resistant if also resistant to Lamivudine

Question 8

Ribavirin

Drug Class, Mechanisms of Action (4), Contraindications (2)

Answer 8

Nulceoside guanosine analog

Interferes with GTP synthesis
Inhibits Viral mRNA capping
Inhibits viral RNA-dependent polymerase
Upregulates ISG activity (potentiates interferons)

Anemia
Pregnancy

Question 9

NS3/NS4A Protease Inhibitors

Mechanism of Action (2) and Examples (3)

Answer 9

Inhibit serine proteases to stop HCV postranslational processing and replication

Grazoprevir
Paritaprevir
Simeprevir (take with food)

Question 10

Grazoprevir

Drug Class and Adverse Effects (3)

Answer 10

NS3/NS4A Protease Inhibitor

Fatigue
Headache
Nausea

Question 11

Paritaprevir

Drug Class and Adverse Effects (4)

Answer 11

NS3/NS4A Protease Inhibitor

Metabolized by CYP3A which causes drug interactions
Nausea
Pruritus
Insomnia

Question 12

NS5B RNA Polymerase Inhibitors

Mechanism of Action and Examples (2)

Answer 12

Block RNA dependent RNA polymerase to decrease HCV replication

Dasabuvir
Sofosbuvir

Question 13

Dasabuvir

Drug Class and Adverse Effects (4)

Answer 13

Non-nucleoside allosteric NS5B inhibitor

Metabolized by CYP3A which causes drug interactions
Nausea
Pruritus
Insomnia

Question 14

Sofosbuvir

Drug Class and Characteristics (2)

Answer 14

Nucleotide NS5B inhibitor

Prodrug
Well tolerated

Question 15

NS5A Inhibitor Examples (4)

Answer 15

Ledipasvir
Ombitasvir
Velpatasvir
Elbasvir

Question 16

Elbasvir
Drug Combination (2) and Adverse Effects (4)

Answer 16

Elbasvir + Grazoprevir

Metabolized by CYP3A so drug interactions
Fatigue
Headache
Nausea

Question 17

Ombitasvir
Drug Combination (5) and Adverse Effects (3)

Answer 17

Ombitasvir + Paratiprevir + Ritonavir + Dasabuvir + Ribavirin

Nausea
Pruritus
Insomnia

Question 18

Velpatasvir
Drug Combination (2) and Adverse Effects (2)

Answer 18

Velpatasvir + Sofosbuvir
*First pangenotypic drug combo

Headache
Fatigue

Question 19

Ledipasvir
Drug Combination (2) and Adverse Effects (3)

Answer 19

Ledipasvir + Sofosbuvir

Headache
Fatigue
Asthenia