Session 5 - Anti-virals

Question 1

Outline the lifecycle of influenze

Answer 1

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

Question 2

What are the three types of influenze?

Answer 2

A, B and C

Question 3

Where does influenze A reside?

Answer 3

Multiple host species

Question 4

How does Influenza A change?

Answer 4

Antigenic draft and shift

Question 5

How is Influenze B different to A?

Answer 5

Lower mortality

Question 6

What is another name for Influenze C?

Answer 6

Common Cold

Question 7

What process is target in anti-viral therapy?

Answer 7

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

Question 8

Name 2 M2 ion channel blockers

Answer 8

 Amantadine

 Rimantadine

Question 9

What are the indications of M2 ion channel blocker treatment?

Answer 9

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

Question 10

What do M2 ion channel blockers do?

Answer 10

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

Question 11

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

Answer 11

Amantadine more than rimantadine

Question 12

Give four adverse drug reactions to M2 antivirals

Answer 12

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

Question 13

What are M2 ion channel blockers effective against?

Answer 13

Group A, not group B

Question 14

Name two neuramidase inhibitors?

Answer 14

Zanamivir

Oseltamivir

Question 15

How is zanamivir administered?

Answer 15

Inhaled

Question 16

How is osteltamivir inhaled?

Answer 16

Orally

Question 17

What are indications for neuradmidase inhibitors?

Answer 17

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

Question 18

What are some contraindications for neuramidase inhibitors?

Answer 18

 Breast feeding

Question 19

What is the mechanism of action of neuramidase inhibitors?

Answer 19

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

Question 20

Give five adverse drug reactions to neuramidase

Answer 20

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

Question 21

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

Answer 21

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

Question 22

What has to be taken into account when using oseltamivir?

Answer 22

 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.

Question 23

How does timing of initiation of neuramidase inhibitors effect treatment?

Answer 23

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.

Question 24

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

Answer 24

~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.

Question 25

How can neuramidase inhibitors be used prophylactically?

Answer 25

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

Question 26

How has emergence of viral resistance affected neuramidase inhibitors?

Answer 26

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