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Pharmacology > Lecture 8: Anti-Hepatitis Agents > Flashcards

Lecture 8: Anti-Hepatitis Agents Flashcards

1
Q

_____: Inflammatory condition of the liver that often leads to hepatic damage through programmed cell death, apoptosis, or necrosis

A

Hepatitis

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2
Q

True or False: Chronic hepatitis could just be carrier state with or without necrosis

A

True

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3
Q

Chronic Hepatitis is mostly caused by ____ and ___ virus

A

Hep B and Hep C

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4
Q

True or False: Hep B Virus is a single stranded RNA virus while Hep C virus is a DNA virus

A

False - Hep B is double stranded, DNA virus; Hep C is a RNA virus

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5
Q

The life cycle of a Hep B virus involves synthesis of RNA with resultant generation of DNA using the process of _________

A

Reverse transcription

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6
Q

____: The enzyme involved in the process of reverse transcription (as seen in Hep B Virus)

A

Reverse transcriptase

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7
Q

True or False: Hep B multiplication involves RNA replication and RNA Polymerase

A

False - Hep C multiplication involves RNA replication and RNA Polymerase

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8
Q

True or False: Reverse Transcription is central to the replication cycle of Hep C Virus

A

False - it is NOT!

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9
Q

True or False: The treatment of Hep B Virus (HBV) infections are more suppressive rather than curative, whereas for Hep C Virus, it is viral eradication

A

True

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10
Q

Why is therapy for Hep B Virus challenging?

A

Covalently closed circular DNA (cccDNA) can remain stable inside of cell for a long time

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11
Q

Which two interferons can treat Hep B Virus?

A
  1. Recombinant Interferon alpha (IFN-a)
  2. PEGylated IFNa
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12
Q

Adefovir Dipivoxil and Tenofovir Disoproxil are _____ that treat Hep B Virus
A. Interferons
B. Nucleotide Analogs
C. Nucleoside Analogs

A

B. Nucleotide Analogs

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13
Q

Entecavir, Lamivudine, and Telbivudine are ______ that treat Hep B Virus:
A. Interferons
B. NucleoTIDE Analogs
C. NucleoSIDE Analogs

A

C. NucleoSIDE Analogs

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14
Q

True or False: Interferons (IFN-alpha and Pegylated IFN-alpha) are common agent for treatment of Hep B and Hep C

A

True

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15
Q

What is the benefit of having a pegylated form of IFN-alpha?

A

LESS of an autoimmune response compared to INF-alpha

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16
Q

Interferons act to stimulate ____ signaling pathway

A

JAK-STAT

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17
Q

True or False: Pegylated IFN are generated better tolerated than recombinant non-pegylated IFN’s, showing less auto-immune trigger

A

True

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18
Q

Adefovir and Tenefovir are acyclic nucleotide analogs of ____

A

AMP (adenosine monophosphate)

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19
Q

Once Adefovir dipivocil and Tenefovir disoproxil enters the cell, it is de-esterified to ____/_____

A

Adefovir and Tenefovir

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20
Q

True or False: The monophosphate form of Adefovir/Tenefovir acts as a competitive inhibit for:
1) Viral DNAP
2) Reverse transcriptase
3) Chain termination of viral DNA synthesis

A

False - the DIPHOSPHATE form does this…

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21
Q

Which two molecules can be inhibited by the diphosphate form of Adefovir and Tenefovir?

A

1) Viral DNAP
2) Reverse transcriptase activity

Leads to: chain termination of viral DNA synthesis

22
Q

True or False: If there is a molecule in the relaxed, closed DNA state, Adefovir/Tenefovir cannot act on it

A

True

23
Q

True or False: High IV administration of Adefovir has been associated with maternal toxicity, nephrotox, embryotox, fetal malformation

A

True

24
Q

____: A guanosine analog that has to undergo intracellular phosphorylation to Entecavir triphosphate

A

Entecavir

25
Q

If one uses entecavir, the formed triphosphate competes with endogenous deoxyguanosine triphosphate and, as a result, inhibits which three processes?

A
  1. Base priming
  2. Reverse transcription from RNA
  3. Synthesis of positive strand of HBV DNA
26
Q

What are the two major AE associated with Entecavir, a nucleoside analog?

A
  1. Lactic acidosis
  2. Severe hepatomegaly
27
Q

What are two features that Lamivudine and Telbivudine have in common?

A

Both are
1. nucleosides
2. have to be converted by cellular kinases to active, triphosphate form

28
Q

____ is a deoxycytidine analog (nucleotide) which then gets converted to triphosphate form

____ is a thymidine analog, which gets converted to triphosphate form

A

Lamivudine
Telbivudine

29
Q

Lamivudine triphosphate and Telbivudine triphosphate competes with endogenous ______ and _______, respectively, for DNAP enzyme of Hep B Virus.

What is the effect of this?

A

deoxycytidine triphosphate
deoxythymidine triphosphate

Effect: Hep B Virus DNA Termination

30
Q

True or False: Lamivudine and Telbivudine inhibit reverse transcription and strand synthesis

A

True

31
Q

___ is a purine nucleoside analog use to treat Hep C Virus
A. Lamivudine
B. Telbivudine
C. Entecavir
D. Ribavirin

A

D. Ribavirin

32
Q

Ribavirin (RBV-monophosphate) competitively inhibits cellular _____, leading to decreased GTP and nucleic acid synthesis

A

Inosine 5 phosphate dehydrogenase

33
Q

How does RBV triphosphate lead to less infective virions? Prevent replication?

A

Leads to less infective virions = promotes hypermutagenesis
Prevents replication = competitively inhibits GTP-5’ capping of viral RNA

34
Q

True or False: Anemia is an AE associated with Ribavirin, as well as elevated serum Fe, bilirubin, and uric acid concentrations

A

True

35
Q

Which two Hep C Virus proteins have cleavage activity?
A. NS5B and NSA5A
B. NS5A, NS4A
D. NS3, NS4A

A

D. NS3, NS4A

36
Q

Which Hep C Virus polypeptide protein forms membranous web and is involved in replication and virus assembly?
A. NS3
B. NS4A
C. NS4B
D. NS5A
E. NS5B

A

D. NS5A

37
Q

Which Hep C Virus Polypeptide protein is RNA dependent and functions with RNAP?
A. NS3
B. NS4A
C. NS4B
D. NS5A
E. NS5B

A

E. NS5B

38
Q

Which of the following TWO drugs are first generation NS3/4A Protease Inhibitors?
A. Boceprevir
B. Glecaprevir
C. Simeprevir
D. Paritaprevir
E. Telaprevir

A

A. Boceprevir
E. Telaprevir

39
Q

True or False: Simeprevir, Paritaprevir, Voxilaprevir, and Glecapreir are second generation NS3/4A Protease Inhibitors and have LESS side effects

A

True

40
Q

True or False: NS3 and 4A, as well as NS4B, NS5A, and NS5B are all structural proteins

A

False - all non-structural proteins

41
Q

______ prevents the NS3/4A mediated polyprotein cleavage

A

NS3/4A Protease Inhibitors

42
Q

Which four drugs are NS5A inhibitors?

A

Ledipasvir
Ombitasvir
Velpatasvir
Daclatasvir

43
Q

NSA5 is a phosphoprotein that contains domains 1, 2, and 3. What are domains 1 and 2 involved in? Domain 3?

A

Domain 1 and 2: RNA replication
Domain 3: Virion assembly

44
Q

On binding to ___, the inhibitors cause a conformational change, thus forming a barrier for ____ interaction with cellular proteins and membrane residing proteins. As a result virus web formation and RNA replication are ____

A

NSA5; hindered

45
Q

NS5A inhibitors block replication of ___ RNA Synthesis and assembly of ___

A

HCV; the virus

46
Q

Which class of drug do Dasabuvir and Sofosbuvir belong to?
A. NS5B Inhibitors
B. NS5A Inhibitors
C. Nucleoside Analog
D. Direct NS3/4A Protease Inhibitors

A

A. NS5B Inhibitors

47
Q

____: an RNA dependent RNAP, which regulates viral RNA genome to produce daughter copies of genetic material
A. NS3
B. NS4A
C. NS4B
D. NS5A
E. NS5B

A

E. NS5B

48
Q

True or False: In all the HCV genotypes, the RNA dependent RNA polymerase structure is fully conserved

A

True

49
Q

____ is a uridine triphosphate analog that undergoes phosphorylation inside hepatic cell to triphosphate form, which then competes w endogenous nucleotide substrates that get incorporated into nascent RNA chain
A. Dasabuvir
B. Sofosbuvir

A

B. Sofosbuvir

50
Q

True or False: Sofosbuvir leads to chain termination and prevents viral RNA replication

A

True

51
Q

____ interacts with RNA-dependent-RNA-Polymerases at one of the four non-catalytic allosteric binding sites, inhibiting the RNAP activity
A. Sofosbuvir
B. Dasabuvir

A

B. Dasabuvir

Pharmacology (53 decks)

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