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GI > PHARM: Drugs for Hep B and Hep C > Flashcards

PHARM: Drugs for Hep B and Hep C Flashcards

1
Q

What is the front-line therapy for chronic HBV?

A

orally active antivirals:
Tenofovir disoproxil fumarate (PMPA)
Entecavir

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2
Q

What HBV drugs are also good for HIV?

A

Tenofovir disoproxil fumarate
Entecavir (weakly)
Emtricitabine

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3
Q

Which HBV drug is actually only approved to treat HIV?

A

Emtricitabine

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4
Q

Which drugs are good for HCV/HBV co-infection?

A

Ribavirin
Peginterferon alpha-2a
Peginterferon alpha-2b

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5
Q

Why do you use combination treatment to treat HBV?

A

reduces resistance (not necessarily more effective)

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6
Q

How does resistance to treatment occur in HBV?

A

mutations in HBV polymerase that is structure specific for the nucleoside/tide structural analogs

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7
Q

How should the first viriologic breakthrough in HBV be managed?

A

“add-on” strategy rather than by sequential monotherapy

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8
Q

What determines first line therapy for chronic HCV?

A

Genotype

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9
Q

What is the common treatment factor in all genotypes of HCV?

A

Peginterferon alpha & Ribavirin (24-48 weeks)

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10
Q

What can you add on for genotype 1 HCV treatment?

A

HCV NS3/4A protease inhibitors

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11
Q

What are the HCV NS3/4A protease inhibitors (for treatment of genotype 1 HCV)?

A

Telaprevir or Boceprevir or Simeprevir

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12
Q

What can you add on for genotype 2-4 HCV treatment?

A

HCV NS5B RNA polymerase inhibitor

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13
Q

What is the HCV NS5B RNA polymerase inhibitor?

A

Sofosbuvir

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14
Q

MOA: Diphosphate form inhibits HBV polymerase and produces chain termination

A

Tenofovir Disoproxil

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15
Q

MOA: Guanosine nucleoside analog (triphosphate form inhibits HBV polymerase)

A

Entecavir

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16
Q

MOA: L-isomer of thymidine (triphosphate form inhibits HBV polymerase and produces chain termination)

A

Telbivudine

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17
Q

MOA: Adenosine-5-monosphsphate (diphosphate form incorporated into viral DNA producing chain termination)

A

Adefovir dipivoxil

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18
Q

MOA: L-isomers of cytosine with similar activity, potency, side effects and patterns of resistance (triphosphate form inhibits HBV polymerase).

A

Lamivudine

Emtricitabine

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19
Q

Should you use lamivudine and emtricitabine together?

A

Don’t use together (no benefit)

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20
Q

MOA: Binds to cell surface receptor to activate TKs that lead to the production of several enzymes like endoribonucleases (cleave ssRNA of virus), inhibitory effects on dsRNA, inhibition of viral replication cycle, enhance lytic effects of cytotoxic T cells.

A

interferons

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21
Q

Although HBV oral drugs have NO CYP interactions, where might they have problems with DDIs?

A

competitive renal secretory mechanisms may be an opportunity for DDIs

22
Q

Other than viral HBV polymerase, what is inhibited by the HBV oral drugs?

A

micochondrial DNA polymerase gamma (essential for mitochondrial DNA replication→ organs cannot generate enough energy to work!)

23
Q

What group of people are most likely to experience hepatic toxicity from HBV drugs?

A

women, obese patients, and alcoholics with prolonged drug exposure.

24
Q

What drug has increased bioavailability if taken with fatty foods?

A

tenofovir disoproxil

25
Q

TOXICITY: Acute renal failure (pts with systemic/renal disease or concurrent nephrotoxic drugs usually)—test for serum creatinine/BUN and phosphate; avoid NSAIDs; Proximal renal tubulopathy: ask about worsening bone pain, pain in extremities and muscles, and fractures (increased risk of osteoporosis—give vitamin D/ Ca2+); also screen LFTs for hepatic toxicity

A

tenofovir disoproxil

26
Q

TOXICITY: risk of renal problems; test for serum creatinine/BUN and phosphate; also screen LFTs for hepatic toxicity

A

entecavir
adefovir dipivoxil
telvibudine

27
Q

TOXICITY: risk for renal problems

A

Lamivudine

Emtricitabine

28
Q

DOSE LIMITING TOXICITY: neuropsychiatric issues (ex. depression, somnolence, confusion, behavioral changes, seizures (rare); ANEMIA, myelosuppression; thyroid dysfunction; hepatic toxicity (increase hepatic enzymes and TGs)

A

Interferons

29
Q

Which type of hepatitis has worse depression with interferons?

A

HCV> HBV

30
Q

Which HBV drug has a ~130 hr T1/2?

A

Entecavir

31
Q

Oral HBV drugs must have altered doses with what conditions?

A

renal dysfunction

32
Q

Why do some antivirals cause chain termination?

A

lacks the 3’-OH group so nothing can attach

33
Q

The toxicity of tenofovir is mainly due to what?

A

accumulation within the cell due to malfunctioning of pump system (drug requires energy dependent pumps to get it into lumen)

34
Q

What renal receptors take up tenofovir from blood?

A

OAT1

35
Q

Mutation of what membrane pump prevents renal cells from emptying tenofovir into lumen for excretion?

A

Mrp4

36
Q

What is the only treatment for HBV given by IV injection?

A

Interferon alpha-2a

37
Q

MOA: Enhance host T cell immune clearance of HCV, inhibit host IMPDH (depletion of pools of GTP→ none for viral RNA synthesis), direct inhibition of RNA-dependent-RNA poly, and RNA virus mutagenesis (drives HCV to error catastrophe).

A

Ribavirin

38
Q

True or false: Ribavirin can return aminotransferase levels to normal

A

TRUE

39
Q

MOA: HCV NS3/4A protease inhibitors (prevent formation of several of the critical non-structural proteins).

A

Boceprevir
Telaprevir
Simeprevir

40
Q

MOA: HCV NS5B RNA polymerase inhibitor

A

Sofosbuvir

41
Q

What drug has synergism with interferon (reduce risk of relapse)?

A

ribavirin

42
Q

How does HCV resistance to NS3/4A protease inhibitors occur?

A

Resistance can occur as the various quasi-species are formed (viral variants with changes in NS proteases).

43
Q

TOXICITY: HEMOLYTIC ANEMIA is major (within 1-2 weeks of initiation; monitor hematocrit), fatal and non-fatal MI as well as difficulty breathing reported (secondary to anemia

A

Ribavirin (presents with jaundice, dark urine, etc.)

44
Q

BBW: DRESS

A

Telaprevir

45
Q

TOXICITY: Rash, pruritis, nausea, myalgia, dyspnea.

A

Boceprevir
Telaprevir
Simeprevir

46
Q

CONTRAINDICATED: women in pregnancy, women who could become pregnant (use 2 forms of BC during pregnancy and for 6 months after), men whose partners are pregnant.

A

Ribavirin
Boceprevir
Telaprevir
Simeprevir

47
Q

In what drugs would you see increased levels of P-gp pumping drug back into lumen and decreasing bioavailability?

A

Boceprevir
Telaprevir
Simeprevir

48
Q

Do Boceprevir, Telaprevir, and Simeprevir have potential for CYP interactions?

A

YES

49
Q

What drug will NOT have exacerbation of anemia if taken with peginterferon/ribavirin?

A

simeprevir

50
Q

What drug for HCV is EXTREMELY expensive?

A

sofosbuvir

51
Q

Why does HCV have lots of problems with resistance?

A

RNA virus

GI (21 decks)

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