11. Drugs to treat Influenza

11. Drugs to treat Influenza

Answered by Lyndsee

There are three serotypes of Influenza virus, A, B and C. Type B and C cause relatively few cases of flu (B will cause Reye’s disease in children) so the majority of flus are caused by type A. The flu is particularly dangerous because of antigenic drift and shift. Antigenic drift is point mutations that occur randomly in the RNA during transcription. Antigenic shift is the exchange of genetic information. While a vaccine has been developed against influenza, it is only able to provide immunity from three strains (if it is a multivalent vaccine), and only for a limited time period. In most cases immunity will last for no more than three years for that particular strain. However, due to constant antigenic drift and antigenic shift, the vaccine often becomes obsolete. A major problem with vaccines is that they’re difficult to culture using egged embryos. Also the strains of virus that kill poultry will also kill the egg embryo. A new technology developed to cope with these issues uses ‘reverse genetics’, whereby the viral RNA genome is converted back to DNA where manipulation to remove the pathogenic genes occurs. The genome is then converted back to RNA for vaccine production, which makes a safer non-pathogenic version of the virus that also grows more effectively in culture or egg embryo.

Amanatadine is an available, relatively cheap drug effective in the prophylaxis and also treatment of Influenza A virus. Its mechanism of action is to prevent viral uncoating of the virus upon entry into the cell. This prevents further replication of the virus due to the inhibition of viral RNA release. The process is carried out by altering the activity of the M2 protein on the membrane of influenza infected cells. This blocks the M2 ion channel. Amantadine is directed at individuals at greater risk of influenza (the elderly etc), as a prophylactic treatment. Amanatadine is also useful for those for whom the influenza vaccine is contraindicated. Amanatadine can also be given in conjunction with the vaccine, as it does not alter the vaccine’s efficacy. However amantadine is not effective against influenza-B virus or parainfluenza virus.

Amantadine is administered as a capsule, tablet or syrup. It has been shown to be 70-90% effective but adverse reactions include confusion, anxiety, insomnia, dry mouth, blurred vision, urinary retention, constipation and hallucinations. These side effects are more common in the elderly. These effects can disappear after the first week of therapy. Caution should be exercised when administering the drug to patients already taking anticholinergic medications as it may exacerbate the anticholinergic effects leading to seizures. There is also a risk of resistance developing and those taking amantadine should be kept separate from high risk contacts.

Rimantadine is another available drug similar to amantadine, however produces less side effects. Rimantadine cannot be administered to children. Rimantadine is only a little more expensive than amantadine.

Zanamivir is a selective neuraminidase inhibitor. Neuraminidase normally cleaves salicylic acid from host and viral cell surfaces facilitating the release of progeny virus from the infected host cell. Zanamivir prevents this cleavage, causing nascent viruses to clump at the host cell surface, causing a reduction in numbers of active virus. Neuraminidase is found in all strains of virus and thus is effective against all strains, unlike amantadine. It can be administered via oral inhalation which delivers the drug directly into the pulmonary site of influenza infection and minimizes systemic exposure. Risk of resistance developing is also minimal, due to the specific binding of Zanamivir onto highly conserves portions of the influenza A and B neuraminidase. No significant side effects have been experienced with Zanamivir; however the drug should be given with caution to patients with chronic obstructive pulmonary disease because of bronchospasm or lung function decline risk.

Tamiflu, another neuraminidase inhibitor is available in pill form. It is also proposed to alter virus particle aggregation and release. While very similar to Zanamivir, its side effects include nausea, vomiting, abdominal pain, dizziness, cough and fatigue. It’s also contraindicated in patients with an oseltamivir phosphate allergy.

Influenza often increases the risk of the development of a bacterial infection (opportunistic). Thus treatment often includes antibiotics.