Anti-viral Pharm for Hep B and C infx (Fitz) Flashcards

1
Q

list the biological agents used for tx of chronic hep B infx

A

IFN alpha-2b
PEG-IFN alpha-2b
PEGylated IFN alpha-2a

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2
Q

list the nucleos(t)ide reverse transcriptase inhibitors used for tx of chronic hep B infx

A

Entecavir (guanosine)
Tenofovor (adenosine) for HBV and HIV
Lamivudine (cytosine) for HBV and HIV
Telbivudine (thymidine)

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3
Q

this class of hepatitis drugs are primarly used for tx of pts with well-compensated liver disease who do not wish to be on long-term tx or are planning to be pregnant within the next 2 or 3 years

A

IFN-alpha formulations

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4
Q

list some cons for the use of IFN-a or PEG-IFN-a tx of chronic HBV infx:

A

DANGEROUS IN DECOMPENSATED CIRRHOSIS
parenteral
expensive
side effects such as flu-like syndrome, fever, myalgia

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5
Q

the ISGF3:DNA complex upregulates this transcription factor through the use of IFN-a

A

IFN stimulated genes (ISG)

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6
Q

ISG degrades viral RNA through this MOA:

A

ISG –> 2’5’ OAS –> 2’5’-AAA activates Ribonuclease L

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7
Q

ISG inhibits protein synthesis through this MOA:

A

ISG –> PKR –> Phospho-eIF

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8
Q

IFN-a (via IFN-y) favors this immune-mediated phenotype and ultimately leads to this negative effect:

A

cell-mediated Th1

increased inflammation and fibrosis

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9
Q

aside from decompensated cirrhosis, what are some other adverse effects of IFN-a?

A

Flu-like syndrome after injection
fatigue and mental depression

Dose-limiting toxicity: BM suppression; Neurotoxicity-behavioral changes

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10
Q

when are nucleoside or nucleotide analog viral RT inhibitors with potent anti-HBV activity used?

A

for chronic, suppressive, oral single agent tx

These are much better tolerated than IFN-containing regimens but are NOT USUALLY CURATIVE.

CAN BE USED IN PTS WITH DECOMPENSATED OR COMPENSATED CIRRHOSIS

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11
Q

what is the MOA of nucleos(t)ides?

A

inhibit viral RT/DNA polymerase

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12
Q

NRTIs are pro-drugs that require conversion into their corresponding __, which are the ACTIVE anti-viral agents, in hepatocytes harboring HBV

A

nucleotide tri-phosphates

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13
Q

list some HBV resistance mechanisms to nucleos(t)ides

A
  • impaired purine/pyrimidine kinase activity

- mutation of DNA polymerase

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14
Q

this nucleotide analog is usueful in pts resistant to lamivudine, telbivudine, and entecavir

A

tenofovir

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15
Q

list the 1st line oral anti-HBV agents

A

tenofovir

entecavir

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16
Q

list the 2nd line oral anti-HBV agents

A

lamivudine

telbivudine

17
Q

__ is a 1st line tx for wild-type HBV, and as an additional tx in pts with lamivudine, telbivudine, or entecavir resistance

A

tenofovir

resistant to tenofovir is rare

nephrotoxicity has been encountered at the dose used for HBV tx but occurs more often with higher doses used for HIV tx

18
Q

this 1st line oral anti-HBV agent has potent anti-viral activiy and a low rate of drug resistance. It may be Resistance to this drug occurs in ~50% of lamivudine-resistant pts after 5 yrs of tx. it may be a better option than adefovir or tenofovir in pts with renal insufficiency and in those who are at risk for renal insufficiency

A

Entecavir

19
Q

long-term efficacy of lamivudine is limited by ___

A

frequent emergence of drug-resistant HBV (YMDD –> YVDD mutant in catalytic domain of HBV polymerase) and subsequent virological breakthrough

20
Q

list the biological agents used to tx hep C infx

A

PEG-IFN a-2b

Pegylated IFN a-2a

21
Q

list a nucleoside used to tx hep C infx

A

Ribavirin

22
Q

list direct acting anti-viral agents used to tx hep C infx

A

Simeprevir (NS3/4A protease)
Sofosbuvir (NS5B RNA dependent RNA polymerase)
Ledipasvir (NS5A)

23
Q

what is the HCV infx standard of care (through 2011)?

A

PEG-interferon PLUS ribavirin for 24-48 weeks

24
Q

Ribavirin-monophosphate has what anti-viral effect in hep C tx?

A

inhibits IMP dehydrogenase –> inhibits purine synthesis and salvage

25
Q

Ribavirin-triphosphate has what anti-viral effect in hep C tx?

A

inhibits RNA-dependent RNA polymerase –> inhibits RNA replication

26
Q

what is the immunomodulatory MOA of ribavirin?

A

potentiates IFN action. Alters the balance between proinflammatory (Th1 and Th2) cytokines

27
Q

how is ribavirin metabolized? How is it cleared? where does it tend to get concentrated?

A

hepatic metabolism

renal clearance (t1/2 ~1 day)

60x concentrated in erythrocytes (t1/2 ~40 days!!)

28
Q

List contraindications of ribavirin:

A
  • causes hemolytic anemia and is contraindicated in pts with anemia
  • Pregnancy category X. May cause birth defects and fetal death. Pts must have a negative pregancy test prior to therapy and have monthly pregnancy test during therapy and 6 months post therapy
29
Q

direct-acting anti-viral agents interfere with HCV replication by inhibiting key viral enzymes such as __

A

NS3/4A serine protease, NS5B polymerase, and NS5A

30
Q

simeprevir is a __ inhibitor

A

NS3/4A protease inhibitor

31
Q

Ledipsasvir is a __ inhibitor

A

NS5A inhibitor

32
Q

Sofosbuvir is a ___ inhibitor

A

NS5B polymerase inhibitor

33
Q

__ block the NS3 catalytic site or the NS3/4A interaction

A

protease inhibitors

34
Q

__ is a 2nd gen protease inhibitor. Used in combo with PEG-IFN and ribavirin or in combo with sofosbuvir +/- ribavrin for chronic genotype 1 infx

A

simeprevir

35
Q

these inhibitors play a role in both viral replication and the assembly of the HCV

A

NS5A inhibitors

36
Q

__ is a potent inhibitor of NS5A, effective across all genotypes, but with a low barrier to resistance. NS5A inhibitors significantly reduce HCV RNA levels when given with PEG-IFN and ribavirin

A

Ledipasvir

37
Q

__ is the first NS5B inhibitor availabe in the US. It is used in combo with other anti-virals, including Ledipasvir

A

Sofosbuvir