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Barts year 3 semester 1 > Antiviral therapy > Flashcards

Antiviral therapy Flashcards

1
Q

Where can anti-viral drugs intervene in the life-cycle of a virus?

A
  • Docking on
  • Membrane fusion, escape from the vacuole, uncoating
  • Replication of DNA/RNA
  • Integration of DNA into the genome
  • Translation of viral RNA to protein
  • Assembly and maturation of virions
  • Escape from the host cell
    ALSO can work by enhancing immune response
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2
Q

What kind of viruses do not integrate their genetic code into the genome of the cell?

A

Pox viruses

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3
Q

What is the enzyme called that encorporates the virus’ genetic code into the host cell’s genome?

A

Integrase

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4
Q

What viruses is Aciclovir (and valaciclovir) effective against?

A
  • Herpes Simplex Virus 1
  • Herpes Simplex Virus 2
  • Herpes Zoster virus
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5
Q

What are aciclovir and valaciclovir analogues of?

A

Guanosine (it is acyclo-guanosine)

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6
Q

What is aciclovir converted into?

A
  • Converted by the viral thymidine kinase to monophosphate acyclo-GMP
  • Human enzyme converts it to a triphosphate
  • Then used by DNA polymerase
  • Viral DNA polymerase used far more readily than the human and causes chain terminations
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7
Q

How can aciclovir and valaciclovir be administered?

A
  • Topically (e.g cold sores or to the eye)
  • Orally
  • IV
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8
Q

What are some side-effects of aciclovir and valaciclovir?

A
  • Cotard’s syndrome (belief that one is already dead)

- Overdose may lead to lethargy, confusion and myoclonus

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9
Q

What has greater oral bioavailability aciclovir or valaciclovir?

A

Valaciclovir

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10
Q

How does resistance occur to aciclovir or valaciclovir?

A

Via mutation of the viral thymidine kinase and/or DNA polymerase

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11
Q

What is idoxuridine used for?

A

Herpes keratitis (too toxic for systemic use)

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12
Q

What was the original treatment for Hep C?

A
  • Ribavirin (now only occasionally used, cheaper)

- Pegylated interferon (interferon alpha or beta)

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13
Q

What drugs are active against CMV?

A
  • Ganciclovir

- Valganciclovir

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14
Q

What are side-effects of ganciclovir and valganciclovir? (anti-CMV drugs)

A

Bone marrow suppression

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15
Q

How does ganciclovir function?

A
  • Synthetic analogue of deoxyguanosine
  • It is phosphorylated to the monophosphate by a CMV thymide kinase and then to the triphosphate by cellular kinases
  • It inhibits viral DNA polymerase more than cellular DNA polymerase, by being incorporated and acting as a chain terminator
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16
Q

What is the difference between valganciclovir and Ganciclovir?

A
  • Valganciclovir is a valine ester of ganciclovir

- Valganciclovir has greater oral bioavailability

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17
Q

What specific enzyme do retroviruses contain?

A

Reverse transcriptase

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18
Q

How do nucleoside and nucleotide analogues (NRTIs) function?

A

They inhibit reverse transcriptase by being incorporated into the growing DNA chain and then being unable to link to the subsequent base

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19
Q

What is an example of a nucleoside analogue?

A

Lamivudine

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20
Q

How many phosphorylations do nucleoside analogues (such as lamivudine) require for incorporation?

A

3

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21
Q

What viruses can lamivudine be used to treat?

A

Hep B and HIV

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22
Q

What is lamivudine an analogue of?

A

Cytidine

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23
Q

What are some adverse effects of lamivudine?

A
  • Nausea
  • Diarrhoea
  • Fatigue
  • Headaches
  • Cough
  • Pro-inflammatory response
  • Autoimmunity
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24
Q

How many phosphorylations are required for nucleotide analogues (e.g Tenofovir) to become incorporated?

A

2

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25
Q

Give an example of a nucleotide analogue that is used in the treatment of Hep B

A

Tenofovir

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26
Q

What is tenofovir an analogue of?

A

Adenosine monophosphate

27
Q

What are adverse effects of tenofovir?

A
  • Renal insufficiency

- Fanconi syndrome

28
Q

How do non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs) function? (e.g Efavirenz)

A

They bind to reverse transcriptase enzyme but not at the active site - this hampers its activity by distortion etc.

29
Q

Give an example of a non-nucleoside/nucleotide reverse transcriptase inhibitor? (NNRTIs)

A

Efavirenz

30
Q

How do protease inhibitors (e.g darunavir, ritonavir) function?

A

They act by binding viral protease that cuts viral precursor proteins into the components of virion structure

31
Q

What is more effective darunivir or ritonavir?

A

Darunivir is more efffective, lives longer and has higher concentrations. Ritonavir also acts to preserve the protease inhibitors that treat hep C.
Hep C can be treated by protease inhibitors and are different from HIV protease inhibitors, ritonavir preserves both protease inhibitors that affect HIV and Hep C.

32
Q

How do integrase inhibitors work?

A

They inhibit integrase, a viral enzyme that mediates integration of the HIV DNA (produced by reverse transcription) into the host genome

33
Q

How do fusion inhibitors work?

A

They block gp41 on the surface of the HIV virion. Gp 41 mediates fusion between the HIV envelope and the cell membrane

34
Q

How do entry inhibitors work?

A

They block CCR5 (a chemokine) receptor on the surface of the cell, which, together with CD4, enables gp 120 on the surface of the HIV virion to bind to the cell and gain entry

35
Q

What is the most common drug combination for the treatment of HIV?

A
  • 2 Nucleoside/Nucleotide reverse transcriptase inhibitors
  • PLUS another HIV drug (e.g an integrase inhibitor or a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor)
  • Often the combinations come as a combined tablet
36
Q

What should you do if a nucleotide or nucleoside reverse transcriptase inhibitor (e.g tenofovir or abacovir) can’t be used (e.g due to resistance or adverse effects)?

A

Use instead:

  • An intigrase inhibitor plus a booster protease inhibitor
  • OR boosted PI plus Iamivudine
  • OR an integrase inhibitor plus iamivudine
37
Q

What anti-virals are included in PrEP?

A

Tenofovir plus emtricitabine

38
Q

What are people exposed to HIV or a needlestick injury given?

A
  • Temofovir
  • Emtricitabine
  • Dolutegravir
    28 day course
39
Q

What is Ribavirin made of?

A
  • Guanosine analogue (i.e an RNA precursor analogue)

- Ribo-nucleoside analogue

40
Q

How does Ribavirin function?

A

Inhibits viral RNA-dependant RNA polymerase: incorporated into new RNA chain, will not link, terminates chain

41
Q

What viruses is Ribavirin used to treat?

A

RNA viruses

  • Hep C
  • Viral haemorrhagic fevers
  • Respiratory Syncytial virus
  • Also been used in influenza
42
Q

What are some adverse effects of ribavirin?

A
  • Psychiatric effects (depression)
  • Haemolytic aneamia
  • Bone marrow suppression
43
Q

What are neurominidase inhibitors (e.g Oseltamavir, Zanamivir) used in the treatment of?

A

Influenza

44
Q

Give two examples of neurominidase inhibitors?

A
  • Oseltamivir

- Zanamivir

45
Q

What types of anti-virals can be used to treat influenza?

A
  • Neurominidase inhibitors:
    Oseltamivir, Zanamivir
  • M2 inhibitors (Amantidine, Rimantidine)
  • Ribavirin
46
Q

Describe how neurominidase inhibitors function

A 
Viral neurominidase (on surface of virion) cleaves sialic acid from glycoprotein, allowing release of virion from the host cell, preventing aggregation of virions, and reduces viral inactivation by host mucus. 
- Neurominidase inhibitors obviously stop all of this
47
Q

How does pegylated interferon work (used in treatment of Hep B and sometimes C)?

A
  • Given IV

- Enhance immune response (make ptient feel more ill)

48
Q

What are the new anti-virals which are used to treat Hep C?

A

Direct Acting agents (DAA) (act against non-structural proteins)

  • Protease inhibitors
  • NS5A inhibitors
  • NS5B inhibitors
49
Q

How does tenofovir help fight Hep C?

A
  • Its not active against Hep C protease but does boost the effects of other Hep C drugs by blocking metabolism
50
Q

How do NS5A inhibitor drugs work? (Anti-HepC drugs)

A

It blocks NS5A which is a viral protein which enables assembly

51
Q

How do NS5B inhibitor drugs work? (Anti-HepC drugs)

A

It blocks NS5B which is a viral RNA-dependant RNA polymerase which enables assembly of the virus (acts as an organiser)

52
Q

Why can Hep C be cured completely?

A

RNA virus therefore is not encorporated into the patient’s genome

53
Q

How long typically is a course of anti-virals to treat Hep C?

A

12 weeks

54
Q

What do you need to consider before starting a patient on elimination therapy for hepatitis C?

A
  • Is there liver damage?
  • Have they had a transplant, is it being considered?
  • Are there manifestations outside the liver (e.g cryoglobulinaemia, or kidney damage (glomerulonephritis)?
  • Are they positive for Hepatitis B and/or HIV?
  • Are they drinking alcohol or using (IV) recreational drugs?
  • Which genotype do they have?
  • Have they had previous treatment which failed, either with old drugs (ribavirin plus interferon) or with DAAs?
55
Q

What enzyme does hepatitis B use to incorporate its DNA into the host cell’s genome?

A

Reverse transcriptase

56
Q

What are the 2 most common reverse transcriptase inhibitors which are used in the treatment of hep B?

A
  • Lamivudine

- Tenofovir

57
Q

Can Hep B be completely eliminated from the genome?

A

No

58
Q

What type of hepatitis has an immunisation available?

A

Hep B

59
Q

What drugs can be used against RSV?

A
  • Ribavirine

- Palivizumab (monoclonal antibody against RSV fusion glycoprotein)

60
Q

By what route is RSV given?

A

Inhalation

61
Q

What patients does RSV mainly affect?

A

Infants and young children (causes wheezy bronchiolitis)

62
Q

What kind of drugs are given to treat Ebola?

A

Monoclonal antibodies which block docking on

63
Q

What type of anti-viral drug can be used to treat coronavirus?

A

Remdesavir

- Inhibits RNA-dependant RNA polymerase

Barts year 3 semester 1 (7 decks)

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