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PHARM HBV, HCV Flashcards

1
Q

what are the 2 preferred treatments for chronic HBV?

A

tenofovir or entecavir

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2
Q

Tenofovir disoproxil MOA

A

pro-drug for tenofovir, a nucleotide analog of adenosine-5-monophosphate
-diphosphate form inhibits HBV polymerase & produces chain termination

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3
Q

entecavir MOA

A

guanosine nucleoside analog

triphosphate form inhibits HBV polymerase

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4
Q

adefovir MOA

A

Adenosine-5-monophosphate

diphosphate form incorporated into viral DNA producing chain termination

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5
Q

lamivudine & emtricitabine MOA

A

L-isomers of cytosine with similar activity, potency, side effects & patterns of resistance
-triphosphate form inhibits HBV polymerase

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6
Q

resistance to drugs against HBV are in what enzyme?

A

HBV polymerase

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7
Q

HBV antiviral drug resistance tends to be __________specific (sugar residue)

A

structure

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8
Q

if a pt with HBV was resistant to tenofovir what other drug wouldn’t work in this pt?

A

adefovir

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9
Q

most of the anti-HBV drugs are excreted in the what?

A

urine

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10
Q

which HBV antiviral has the shortest half life?

A

lamivudine

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11
Q

all the orally active anti-HBV drugs have what kind of CYP interactions?

A

NONE

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12
Q

which anti-HBV drug has increased bioavailability when taken with high fat meal?

A

tenofovir disoproxil

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13
Q

food delays absorption of what anti-HBV drug?

A

entecavir

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14
Q

which drug can cause Acute renal failure most often in pts w/ systemic renal dz or concurrent nephrotoxic drugs, sometimes in pts with no risk factors?

A

tenofovir

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15
Q

what lab values should you test before putting a pt on tenofovir?

A

creatinine/ BUN & phosphate

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16
Q

if you are taking tenofovir you should avoid concurrent nephrotoxic agents like what?

A

NSAIDs

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17
Q

which anti-HBV drug is associated with bone pain & bone fractures?

A

tenofovir

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18
Q

bone fractures in pts taking tenofovir can be a manifestation of what?

A

proximal renal tubulopathy

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19
Q

which anti-HBV drug is most likely to cause decreased bone mineral density & increased markers of bone turnover (increased risk of osteoporotic fracture)

A

tenofovir

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20
Q

if you are an HIV pt taking tenofovir, what kind of supplements should you also take?

A

Calcium & vitamin D supplements ( to help reduce decrease in bone mineral density)

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21
Q

lactic acidosis & steatosis are adverse effects of which class of antivirals?

A

nucleoside & nucleotide analog antiretrovirals

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22
Q

what are some risk factors for hepatic toxicity in pts takin anti-HBV drugs?

A

women, obesity, alcoholism, prolonged drug exposure

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23
Q

what lab test do you want to make sure you order for adefovir, telbivudine & entecavir?

A

LFTs

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24
Q

tenofovir is active against which 2 kinds of viruses?

A

HIV & HBV

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25
Q

Which drug is weakly active against HIV and can induce M184V variant that is resistant to lamivudine & emtricitabine?

26
Q

which drug is only approved for HIV pts but is useful in both HIV & HBV coinfected pts?

A

emtricitabine

27
Q

if you have a pt that is coinfected with HBV & HCV what is your initial treatment?

A

initial treatment is peginterferon & ribavirin to target the HCV

28
Q

interferons MOA

A

binds to cell surface receptor to activate tyrosine kinases, which lead to the production of several IFN-stimulated enzymes

  • endoribonucleases cleave ss viral RNA
  • inhibitor effects on dsRNA
  • inhibition of viral penetration & uncoating (&/o viral assembly & release)
  • enhanced lytic effects of cytotoxic T lymphocytes
29
Q

interferons activate what kind of Tyrosine kinase receptors?

A

JAK/STAT TK receptors

30
Q

which antiviral drug will cause an acute influenza-like syndrome following injection?

A

fever, chills, headache, myalgia, arthralgia, nausea, vomiting, diarrhea (pt becomes tolerized over time)

31
Q

what kind of neuropsychiatric issues can IFN cause?

A

depression (higher in HCV pts than HBV pts)

somnolence, confusino, behavioral changes, rarely seizures

32
Q

which anti-HBV/anti-HCV drug can cause myelosuppression, granulocytopenia & thrombocytopenia?

33
Q

increased hepatic enzymes & triglycerides are adverse effects of what anti-viral drug?

A

IFN (hepatotoxicity may occur)

34
Q

what lab values do you need to monitor during IFN therapy?

A 
thyroid function (possible thyrotoxicosis)
hepatic enzymes
35
Q

what is the drug regimen for Genotype 1 of HCV?

A

peg-IFN-alpha + ribavirin (24-48wks) + telaprevir (or boceprevir)

36
Q

what is the drug regimen for genotypes 2 & 3 of HCV?

A

PEG-IFN-alpha + Ribavirin 24-48 wks

37
Q

Ribavirin MOA?

A

enhanced host T-cell clearance

  • inhibits host IMPDH w/ depletion of pools of GTP (needed for viral RNA synth.)
  • direct inhibits HCV replication (via RNA-dependent RNA polymerase)
  • RNA virus mutagenesis that drives HCV to error catastrophe
38
Q

Which anti-HCV drug synergiezes w/ IFN greatly enhancing its activity and reduces risk of viral relapse?

39
Q

which anti-HCV drug has increased bioavailability with high fat meal?

40
Q

name the anti-HCV drug that has a very large volume of distribution with a long half-life?

41
Q

how is ribavirin eliminated?

A

renal elimination

42
Q

what is the primary toxicity of oral ribavirin therapy?

A

hemolytic anemia (10-13% incidence)

43
Q

which antiviral has extensive uptake into cells including rbcs?

A

ribavirin (explains hemolytic anemia)

44
Q

what is the important lab value you have to monitor when using ribavirin?

A

hematocrit

45
Q

name an adverse effect that is secondary to ribavirin-induced anemia?

A

fatal & nonfatal MI

46
Q

which HCV antiviral have male-mediated teratogenicity?

A

ribavirin, beceprevir, telaprevir

47
Q

how do telaprevir and beceprevir work?

A

NS3/4A Serine Protease inhibitors (prevents formation of several critical nonstructural proteins)

48
Q

how are telaprevir & beceprevir administered?

49
Q

telaprevir & beceprevir may not be as effective in what types of pts?

A

african americans

50
Q

what kinds of pts benefit from telaprevir/boceprevir therapy against HCV?

A

treatment naive pts

pts relapsing on combo therapy

51
Q

what are some of the adverse effects of telaprevir/boceprevir?

A

fatigue, anemia, nausea (additive anemia over and above the combo drug effects)

52
Q

which anti-HCV drug has a BBW for serious rash?

A

telaprevir

53
Q

which anti-HCV drug has increased bioavailability with high fat food?

A

TELAPREVIR

54
Q

which anti-HCV drug is an equal mixture of 2 diasteromers, one active, one inactive, rapidly interconvert in plasma?

A

boceprevir

55
Q

name 2 antiviral drugs that extensively bind plasma proteins

A

beceprevir & telaprevir

56
Q

how are beceprevir & telaprevir metabolized and eliminated?

A

hepatic metabolism w/ elimination in stool

57
Q

boceprevir is primarily metabolized by what enzyme but is also a substruate for CYP3A4/5, P-gp?

A

aldoketoreductase

58
Q

name the drug that is a substrate and inhibitor for CYP3A4 & P-gp and an inhibitor of OATP1B1 & OATP2B1

A

TELAPREVIR

59
Q

What is the most frequent adverse effect of boceprevir & telaprevir?

60
Q

what are the big picture downsides to IFN therapy?

A

short half-life
frequent dosing
significant side effects

61
Q

how is IFN administered?

A

IM or SC

prefer to use PEG product which has better sustained serum drug levels & permits once weekly dosing

GI (12 decks)

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