M2 channel blocking agents (adamantanes) amantidine and rimantidine and neuraminidase inhibitors nebulized zanamivir (Relenza) and oral oseltamivir (Tamiflu) have anti influenzal activity.
Adamantanes are active against influenza A viruses.
Adamantanes interfere with viral uncoating intracellularly and are associated with rapid emergence of drug resistant variants.
Adamantane resistant influenza isolates are genetically stable and can be transmitted to susceptible contacts with virulent disease and be shed for prolonged periods of time from immunocompromised hosts.
Because of the potential for development of resistance the adamantanes are limited in their use in the treatment of influenza, but such drugs remain useful for prophylaxis during an epidemic.
Resistance to adamantanes can occur spontaneously or emerge rapidly following treatment.
Recent studies have indicated increasing drug resistance to adamantanes from 1.8% during the 2001-2002 influenza season to 12.3% during the 2003-2004 flu season.
Neuraminidase inhibitors are active against influenza A and B.
Neuraminidase inhibitor resistance remains rare.
Neuraminidase inhibitors zanamivir and oseltamivir interfere with the release of progeny of virus from infected host cells preventing infection of new host cells and stops spread if infection in the respiratory infection.
After the onset of the infection replication of virus reaches peak between 24 and 72 hours in the respiratory tract, indicating that neuraminidase inhibitors acting at the stage of viral replication must be given as early as possible.
Available approved agents include oral oseltamivir (Tamiflu), inhaled zanamivar (Relenza), and inhaled peramivir (Rapivab).
All 3 drugs have a perceived comparable efficacy.
Oseltamivir taken within 48 hours of symptom onset, decrease s duration of influenza by a medium of 70 hours and decreases patient perceived severity of illness (Treanor JJ et al).
Other studies suggest oseltamivir treatment decreases duration of influenza symptoms by 17 hours in adults and 29 hours and children (Jefferson T et al).
Studies suggest early use of oseltamivir does not decrease risk of pneumonia or rates of influenza hospitalizations or deaths.