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Pharm II Exam 1 > Lecture 5: Drugs for Hepatitis > Flashcards

Lecture 5: Drugs for Hepatitis Flashcards

1
Q

What indicates viral load?

A

HCV RNA in the blood

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2
Q

If the RNA is undetectable after 12 wks of treatment with hepatitis drugs what does that indicate?

A

SVR (Sustained Virologic Response) –> aka a cure

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3
Q

What type of drug is Ribavirin?

What other drug can it be used in combination with?

A

Guanosine analog –> mimics guanosine & tricks HCV into using it to replicate

used in combo w/interferons

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4
Q

MOA for Ribavirin?

A

Blocks the capping of viral RNA –> inhibits viral RNA-dependent polyermerase –> induces mutations in the viral RNA –> RNA becomes unfunctional

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5
Q

What is the major toxicity associated w/Ribavirin?

A

Hemolytic anemia

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6
Q

Other than HCV treatment what is Ribavirin also used for?

A
  1. influenza A & B
  2. parainfluenza
  3. RSV
  4. HIV-1
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7
Q

What type of drug are interferons?

A

Cytokines that bind to membrane receptors

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8
Q

Once the interferon alpha binds to the membrane receptor what does it cause?

A

It induces intracellular signals –> inhibit viral penetration, transcription, translation & protein processing, maturation, and release

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9
Q

What are the 3 major effects of interferons based on its MOA? Overall result?

Note: has a direct effect on the virus

A
  1. incr MHC antigens
  2. incr phagocytic activity of macrophages
  3. incr proliferation/survival of cytotoxic T cells

OVERALL: ramps up the immune system to stop the virus

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10
Q

What is the major toxicity associated with interferons?

A

BAD flu like symptoms –> non adherence

reason why these drugs hardly ever used

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11
Q

Other than HCV treatment what are interferons also used for?

A

HBC and tumors (anti-tumor activity)

b/c they exert antiviral, immunomodulatory & anti-proliferative actions

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12
Q

CIs to using interferons?

A
  1. Hepatic decompensation
  2. Autoimmune dz
  3. Hx of cardiac arrhythmia
  4. Severe depression
  5. Pregnancy
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13
Q

What type of drug is Simpreprevir?

A

HCV Protease inhibitor –> targets NS3/4A protease

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14
Q

What are the major toxicities/AEs associated w/Simpreprevir?

A
  1. Rash**
  2. Photosensitivity**
  3. incr bilirubin/uric acid
  4. CI in combo w/ interferons/ribavirin in pregnancy
  5. Drug-Drug interactions w/ statins**(rosuvastatin/atorvastatin)
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15
Q

Use for Simpreprevir?

A

HCV genotype 1

Note: better response than interferon/ribavirin alone

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16
Q

What drug is the prototype for HCV Polymerase/NS5B inhibitors? What type of drug is it?

A

Sofosbuvir

- uridine analog

17
Q

What is the MOA for Sofosbuvir?

A

Targets RNA-dependent HCV RNA polymerase activity

(binds to NS5B protein) –> block RNA synthesis

18
Q

What type of patients should not receive Sofosbuvir?

A

Pts w/severe renal dysfunction –> d/t increased exposure

Note: well tolerated, most toxicities are d/t peg/ribavirin combinations

19
Q

What kind of drugs should not be combined w/ Sofosbuvir? Why?

A

P-gp inducers (rifampin)

- b/c Sofosbuvir is a P-glycoprotein transporter substrate

20
Q

What types of HCV is Sofosbuvir used for?

A

ALL genotypes and those resistant to PIs

21
Q

When is Sofosbuvir is 1st line tx?

A

Sofosbuvir is 1ST LINE TX IN COMBO w/ledipasivir, Ribavirin, or Peginterferons

22
Q

How is Sofosbuvir given to kids > 12 y/o or 77+ lbs?

A
  • Sofosbuvir given alone for genotypes 2/3

- Sofosbuvir + ledipasvir for genotypes 1, 4, 5, 6

23
Q

What drug is the prototype for NS5A inhibitors?

A

Ledipasvir

24
Q

What is the MOA for Ledipasvir?

A

Targets the NS5A protein

Thought to:

  1. block replication (interacts w/NS5B) by preventing RNA from binding to polymerase
  2. inhibit viral assembly andrelase
25
Q

How must Ledipasvir be given? What is not needed?

A

Ledipasvir must be given in combo w/Sofosbuvir
(Ledipasvir + Sofosbuvir = Harvoni)

Peginterferon or Ribavirin is not needed

26
Q

What is the major problem w/Ledipasvir?

A

can lead to resistant mutations

otherwise well tolerated (fatigue, HA)

27
Q

What is Harvoni used for?

A
  1. HCV Genotype 1 –> HIGHEST SVR

2. HCV/HIV co-infection

28
Q

What are the 3 drugs that are oral and interferon free?

A
  1. Zepatier
  2. Eplusca
  3. Mavyret
29
Q

Use for Zepatier (Elbasvir + Grazoprevir)?

A

HCV genotypes 1, 4

Safer than Harvoni for renal impaired pts

30
Q

CI for Zepatier (Elbasvir + Grazoprevir)?

A

Hepatic impairment –> fatal hepatic decompensation

31
Q

Use for Eplusca (Sofosbuvir + Velpatasvir)?

A

ALL genotypes

mod-severe decompensated cirrhosis

32
Q

Use for Mavyret (Pibrentasivir + Glecaprevir)?

A
  1. ALL genotypes
  2. GFR < 30
  3. Less expensive if only need 8wks Tx

Pharm II Exam 1 (6 decks)

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