Anti-virals

Question 1

Name the classes of anti-viral medication used in the therapy of an influenza infection, giving two examples of each.

Answer 1

Amantadanes - rimantadine and amantadine.

Neuraminidase inhibitors - oseltamivir (Tamiflu) and zanamvir

Question 2

Describe the mechanism of action of the amantadanes

Answer 2

Amantadine and rimantadine function by inhibiting the viral M2 ion channel, thereby preventing the viral uncoating. The M2 channel normally allows passage of protons into the viral capsule, reducing pH and triggering uncoating. Without this change in pH the viral genetic complement is not released into the cell.

Question 3

What are the common side effects of amantadine?

Answer 3

Amantadine is also used for Parkinson’s disease and so can have effects on the CNS. These effects include headache, dizziness, mood changes, insomnia, ataxia.

Unrelated to the CNS they also cause symptoms similar to asthma - SOB, chest tightness, wheeze.

Question 4

How do zanamvir/oseltamivir work as antiviral agents in influenza infections?

Answer 4

These drugs are neuraminidase inhibitors. Neuraminidase is a viral surface enzyme and virulence factor which functions to bind and cleave sialic acid on respiratory cell surfaces and in the mucus layer. By doing this the virus is able to navigate through the mucus layer more efficiently. Loss of this function due to inhibition results in an inability to pass through the layer and also difficulty in releasing from the cell, which also uses attachment to sialic acid.

Question 5

Comment on the bioavailability of zanamvir and oseltamivir.

Answer 5

Oseltamivir has a high bioavailability (80%) and so can be taken orally, both for treatment of infection and post exposure prophylaxis.
Zanamvir has a poor oral bioavailability and so is given as an inhaled powder directly into the respiratory tract. It can also be use in treatment and post exposure prophylaxis.

Question 6

During what time period is treatment for influenza using oseltamivir indicated?

Answer 6

Oseltamivir treatment should be started within 48 hours of onset of symptoms. It has the greatest effect a few hours after onset of symptoms and reduces the during of the disease significantly. If commented within 64 hours it still significantly reduces mortality from influenza.

Question 7

Describe the adverse effects of oseltamivir.

Answer 7

The most frequently reported side effects are nose bleeds, abdominal pain and vomiting.