Session 5 - Anti-virals Flashcards

1
Q

Outline the lifecycle of influenze

A
  1. Influenza virus binds to cell via Hemagglutinin onto sialic acid sugars on the surface of epithelial cells.
  2. Entry of virus into cell via endocytosis
  3. ATP driven proton entry into the endosome, allowing fusion of the viral membrane with the internal endosomal membrane
  4. Entry of protons into the virus itself via the viral M2 Ion Channel. Low pH inside the virus results in breakdown in the viral coat of the nucleocapsid core. This releases viral RNA into the host cytoplasm
  5. Virus replicates using host cell machinery
  6. Viral protein assembly
  7. New virus buds off the cell membrane, but many remain attached by re-attaching to the sialic acid on the cell surface
  8. Viral Neuramidase enzyme breaks this bond, allowing viral release
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2
Q

What are the three types of influenze?

A

A, B and C

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3
Q

Where does influenze A reside?

A

Multiple host species

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4
Q

How does Influenza A change?

A

Antigenic draft and shift

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5
Q

How is Influenze B different to A?

A

Lower mortality

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6
Q

What is another name for Influenze C?

A

Common Cold

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7
Q

What process is target in anti-viral therapy?

A
  1. Entry of protons into the virus itself via the viral M2 Ion Channel. Low pH inside the virus results in breakdown in the viral coat of the nucleocapsid core. This releases viral RNA into the host cytoplasm
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8
Q

Name 2 M2 ion channel blockers

A

 Amantadine

 Rimantadine

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9
Q

What are the indications of M2 ion channel blocker treatment?

A

 Prophylaxis and treatment of acute Influenza A in groups at risk.

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10
Q

What do M2 ion channel blockers do?

A

 Blocks M2 Ion Channel, preventing breakdown of viral coat and release of viral RNA into host cell.

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11
Q

Which of the two M2 ion channel blockers has more marked ADR

A

Amantadine more than rimantadine

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12
Q

Give four adverse drug reactions to M2 antivirals

A

 Dizziness
 Hypotension
 GI disturbance
 Confusion, insomnia and hallucination can be problematic in the elderly

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13
Q

What are M2 ion channel blockers effective against?

A

Group A, not group B

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14
Q

Name two neuramidase inhibitors?

A

Zanamivir

Oseltamivir

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15
Q

How is zanamivir administered?

A

Inhaled

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16
Q

How is osteltamivir inhaled?

A

Orally

17
Q

What are indications for neuradmidase inhibitors?

A

 Treatment of Influenza A or B virus within 48 hours after onset of symptoms when influenza is endemic in the community

18
Q

What are some contraindications for neuramidase inhibitors?

A

 Breast feeding

19
Q

What is the mechanism of action of neuramidase inhibitors?

A

 Sialic acid analogues, with very high binding affinities for Neuramidase.
 Prevents release of newly formed viruses

20
Q

Give five adverse drug reactions to neuramidase

A
o	Headache
o	Nose bleed
o	Respiratory depression (rarely)
o	Bronchospasm
o	GI disturbances
21
Q

What has to be taken into account when giving zanamivir as treatment?

A

given as an aerosol, has low bioavailability and can only be used for treatment.

22
Q

What has to be taken into account when using oseltamivir?

A

 Oseltamivir is a pro-drug and by contrast is well absorbed, with 80% bioavailability. This enables it to be given orally for both treatment and prophylaxis.

23
Q

How does timing of initiation of neuramidase inhibitors effect treatment?

A

The earlier treatment is started after symptom onset, the shorter the duration of symptoms. The time window for significant reduction goes up to 48 hours, little benefit accrues after this time.

24
Q

What is the reduction in risk of mortality after oseltamivir treatment?

A

~70% reduction in risk of mortality according to one Canadian study. This was achieved when dosing was delayed as long as 64 hours after symptom onset.

25
Q

How can neuramidase inhibitors be used prophylactically?

A

Treatment for six weeks with 75mg significantly reduced incidence of flu in both healthy adults and frail elderly subjects.

26
Q

How has emergence of viral resistance affected neuramidase inhibitors?

A

Some resistance has been reported to Oseltamivir in H1N1 viral strains. Virus still remains sensitive to Zanamivir.