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Pharmacology (Topic C) > 7. Agents against hepatitis viruses > Flashcards

7. Agents against hepatitis viruses Flashcards

1
Q

List the interferons.

A
  1. Interferon Alpha
  2. Interferon Beta
  3. Interferon Gamma
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2
Q

List the Anti-HCV drugs.

A
  1. Ribavirin
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3
Q

List the polymerase inhibitors.

A
  1. Sofosbuvir - a nucleoside analog
  2. Dasabuvir - a non-nucleoside NS5B inhibitor
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4
Q

List the Protease Inhibitors/”NS3-4 inhibitors”.

A
  1. Simeprevir
  2. Other NS3-4A inhibitors include: Boceprevir, Paritaprevir; Grazoprevir; Glecaprevir; Voxilaprevir.
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5
Q

List the NS5A transcription complex inhibitor.

A
  1. Daclatasvir (Monotherapy, all others combo)
  2. Ledipasvir
  3. Ombitasvir
  4. Elbasvir
  5. Velpatasvir
  6. Pibrentasvir
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6
Q

List the combination therapy (common combos).

A
  1. Sofosvir + Velpatasvir
  2. Sofosbuvir +Daclatasvir + Ribavirin + rarely interferon
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7
Q

List the Hep B agents.

A
  1. Interferon alpha +
  2. NRTIs: nucleoside/-tide analogs (Monotherapy)
    • Lamivudine (most used, but not most effective) or Emtricitabine
    • Entecavir
    • Tenofovor
    • Minor ones: Telbivudin + Adefovir
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8
Q

What are the indications for Interferon Beta therapy?

A
  1. Multiple Sclerosis - relapsing-type
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9
Q

What are the indications of Interferon Gamma?

A
  1. Chronic Granulomatous Disease (CGD) - activates macrophages that would otherwise not form superoxide necessary for oxidative bursts.
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10
Q

What are the indications for interferon alpha therapy?

A
  1. Infection with Hepatitis B or C viruses
  2. Neoplasms - hairy cell leukemia, malignant melanoma and renal cell carcinoma
  3. HHV8 - causing Kaposi sarcoma
  4. HPV - causing condyloma acuminata.
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11
Q

What are the kinetic parameters of interferon alpha?

A
  1. Interferon alpha is given parenterally as a subcutaneous injection.
  2. Pegylated versions have ↑ half-life and steadier kinetics.
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12
Q

What are the side effets of interferon alpha therapy?

A
  1. Flu-like syndrome - headache, fever, malaise, myalgia and pneumonitis; within 6 hrs of dosing; in >30% of patients within first week of tx, but resolves
  2. Neurotoxicity - causing fatigue, confusing, tinnitus, retinopathy
  3. Myelosuppression - esp. when with other myelosuppressants (i.e. Zidovudine)
  4. rarely drug-induced lupus - with ANA and anti-dsDNA Abs
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13
Q

What are interferons?

A
  1. Interferons are immunostimulatory cytokines normally released from virus-infected cells.
  2. Interleukins upregulate interferon synthesis in infected cells.
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14
Q

What are the side effects of Ribavirin?

A
  1. Hemolytic Anemia - dose-dependent; in 10-20% pts
  2. Teratogen - contraindicated in pregnancy or adults not using contraception
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15
Q

What is the MOA of Ribavirin?

A

Ribavirin is a guanosine nucleoside analog (P-ated by host enzymes → nucleotide → ↓ RNA synthesis)

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16
Q

What is the MOA of Interferon Alpha?

A

Interferon Alpha - given as recombinant INF-α2a / INF-α2b

***

17
Q

Anti-HCV Drugs

A
  • HCV genotype and fibrosis stage (by history, physical + lab tests) is important in selecting therapy
  • Goal of therapy is eradication of Hep C RNA for 6 months after treatment (so-called “sustained virologic response” or SVR)
  • Traditional treatment was once-weekly pegylated INF-α with daily ribavirin, but newer protease + polymerase inhibitors are used now.
18
Q

What are the indications for Ribavirin?

A
  1. Hepatitis C - 12-48 weeks, once-daily oral; with INF-α (once weekly); can also be IV
  2. RSV - given as aerosol; but mostly replaced by palivizumab
19
Q

What is the MOA of Sofosbuvir?

A

Sofosbuvir inhibits the NS5B RNA-dependent RNA polymerase → ↓ viral RNA production. Can be used with interferon/ribavirin tx, or commonly alone.

20
Q

What are the indications for protease inhibitors?

A

Treatment of Hep C genotype 1 and 4

21
Q

What is the MOA of NS5A Transcription Complex Inhibitors?

A

They inhibit transcription complex with role in viral assembly and replication.

22
Q

What are the most common combinations for combination therapy and how long are they give?

A
  1. Sofosbuvir + Velpatasvir - for 12 weeks
  2. Sofosbuvir + Daclatasvir - 12-24 wks dep. on genotype
  3. Often ribavirin and rarely interferon is added
23
Q

What is the treatment plan for Hepatitis B?

A
  1. INF-α or nucleoside/-tide analogs (NRTIs)usually given as monotherapy
  2. Goal is ↓ viral replication, allow seroconversion, normalize liver enzymes + achieve a ‘sustained viral response’ (virus free 6 months after tx)
24
Q

What is Entecavir?

A

Entecavir is a guanosine analog, well-tolerated and low primary resistance, but mild lamivudine cross-resistance.

25
Q

What is Tenofovir?

A

Tenofovir is a nucleotide analog → no P-ation required

26
Q

What is Telbivudin?

A

Telbivudin is a thymidine analog; well-tolerated; no cross-resistance but fast primary resistance

27
Q

What is Adefovir?

A

Adefovir is a AMP analog; may be nephrotoxic; no cross-resistance, but more primary.

28
Q

What are the indications for Sofosbuvir?

A

Infection with Hep C genotypes 1-6

29
Q

What are the side effects of Sofosbuvir?

A

Well-tolerated, but may cause fatigue, nausea or insomnia.

30
Q

What is the MOA of Dasabuvir?

A

Dasabuvir is a non-nucleoside NS5B inhibitor. Its used in combo with a protease and NS5A transcription inhibitor.

31
Q

What are the side effects of Dasabuvir?

A
  1. Fatigue
  2. Nausea
  3. Vomiting
  4. Itching
32
Q

What are the indications for NS5A transcription complex inhibitors?

A

ALL genotypes of Hep C

33
Q

What are the side effects of NS5A Transcription complex inhibitors?

A

Headache, Nausea and Fatigue.

34
Q

What is the MOA of protease inhibitors?

A

Protease inhibitors inhibits proteases which cleave HCV-encoded polyproteins. Resistance often develops quickly to these drugs.

35
Q

What is the route of administration for protease inhibitors?

A

Given orally

36
Q

What are the side effects of Simeprevir?

A
  1. Photosensitivity - with rash
  2. CYP450 Inhibition - drug interactions
37
Q

What are the side effects of Boceprevir?

A

Causes anemia.

Pharmacology (Topic C) (20 decks)

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