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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
Which drug is weakly active against HIV and can induce M184V variant that is resistant to lamivudine & emtricitabine?
entecavir
26
which drug is only approved for HIV pts but is useful in both HIV & HBV coinfected pts?
emtricitabine
27
if you have a pt that is coinfected with HBV & HCV what is your initial treatment?
initial treatment is peginterferon & ribavirin to target the HCV
28
interferons MOA
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
interferons activate what kind of Tyrosine kinase receptors?
JAK/STAT TK receptors
30
which antiviral drug will cause an acute influenza-like syndrome following injection?
fever, chills, headache, myalgia, arthralgia, nausea, vomiting, diarrhea (pt becomes tolerized over time)
31
what kind of neuropsychiatric issues can IFN cause?
depression (higher in HCV pts than HBV pts) | somnolence, confusino, behavioral changes, rarely seizures
32
which anti-HBV/anti-HCV drug can cause myelosuppression, granulocytopenia & thrombocytopenia?
IFN
33
increased hepatic enzymes & triglycerides are adverse effects of what anti-viral drug?
IFN (hepatotoxicity may occur)
34
what lab values do you need to monitor during IFN therapy?
``` thyroid function (possible thyrotoxicosis) hepatic enzymes ```
35
what is the drug regimen for Genotype 1 of HCV?
peg-IFN-alpha + ribavirin (24-48wks) + telaprevir (or boceprevir)
36
what is the drug regimen for genotypes 2 & 3 of HCV?
PEG-IFN-alpha + Ribavirin 24-48 wks
37
Ribavirin MOA?
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
Which anti-HCV drug synergiezes w/ IFN greatly enhancing its activity and reduces risk of viral relapse?
ribavirin
39
which anti-HCV drug has increased bioavailability with high fat meal?
ribavirin
40
name the anti-HCV drug that has a very large volume of distribution with a long half-life?
ribavirin
41
how is ribavirin eliminated?
renal elimination
42
what is the primary toxicity of oral ribavirin therapy?
hemolytic anemia (10-13% incidence)
43
which antiviral has extensive uptake into cells including rbcs?
ribavirin (explains hemolytic anemia)
44
what is the important lab value you have to monitor when using ribavirin?
hematocrit
45
name an adverse effect that is secondary to ribavirin-induced anemia?
fatal & nonfatal MI
46
which HCV antiviral have male-mediated teratogenicity?
ribavirin, beceprevir, telaprevir
47
how do telaprevir and beceprevir work?
NS3/4A Serine Protease inhibitors (prevents formation of several critical nonstructural proteins)
48
how are telaprevir & beceprevir administered?
orally
49
telaprevir & beceprevir may not be as effective in what types of pts?
african americans
50
what kinds of pts benefit from telaprevir/boceprevir therapy against HCV?
treatment naive pts | pts relapsing on combo therapy
51
what are some of the adverse effects of telaprevir/boceprevir?
fatigue, anemia, nausea (additive anemia over and above the combo drug effects)
52
which anti-HCV drug has a BBW for serious rash?
telaprevir
53
which anti-HCV drug has increased bioavailability with high fat food?
TELAPREVIR
54
which anti-HCV drug is an equal mixture of 2 diasteromers, one active, one inactive, rapidly interconvert in plasma?
boceprevir
55
name 2 antiviral drugs that extensively bind plasma proteins
beceprevir & telaprevir
56
how are beceprevir & telaprevir metabolized and eliminated?
hepatic metabolism w/ elimination in stool
57
boceprevir is primarily metabolized by what enzyme but is also a substruate for CYP3A4/5, P-gp?
aldoketoreductase
58
name the drug that is a substrate and inhibitor for CYP3A4 & P-gp and an inhibitor of OATP1B1 & OATP2B1
TELAPREVIR
59
What is the most frequent adverse effect of boceprevir & telaprevir?
anemia
60
what are the big picture downsides to IFN therapy?
short half-life frequent dosing significant side effects
61
how is IFN administered?
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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