Oseltamivir and Zanamivir

Antiviral Efficacy and Clinical Use. Oseltamivir (Tamiflu) and Zanamivir (Relenza) are effective against influenza virus types A and B. These drugs can reduce the duration and severity of flu symptoms if the drug is administered within 48 hours after symptoms first appear.22,46 These drugs can also be taken pro-phylactically to reduce the risk of getting the flu, especially in people who are at high risk (older adults, people with respiratory disorders), or in cases where an individual is exposed to a family member or someone else with the flu.3 

Mechanism of Action. Oseltamivir and zanamivir inhibit a specific enzyme (neuraminidase) that the influenza virus uses to complete its biosynthesis and release. By inhibiting this enzyme, these drugs impair a key step in viral replication, and reduce the ability of the virus to infect other respiratory cells. 

Adverse Effects. Oral administration of oseltamivir can cause gastrointestinal disturbances such as nausea, vomiting, diarrhea, and abdominal cramps. Zanamivir, which is administered by inhalation, is associated with bronchospasm and reduced opening of the airway. The adverse effects of zanamivir can be quite severe in people with bronconstrictive disease (asthma, chronic obstructive pulmonary disease), and this drug should probably be avoided in these individuals. 

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Further SAR studies on the cyclopentane scaffold have included variation of the hydrophobic side-chain to incorporate a carboxamide substituent (Chand et al. 2004), equivalent to the C6-carboxamide derivatives of zanamivir, and extension of the length of the hydrophobic side-chains (Chand et al. 2005a). Analogues that incorporate a longer 4-heptyl side-chain showed comparable efficacy to 34 upon oral and intranasal administration in mice, and comparable or better efficacy than oseltamivir and zanamivir (Chand et al. 2005a). 

Bantia S, Parker CD, Ananth SL, Horn LL, Andries K, Chand P, Kotian PL, Dehghani A, El Kattan Y, Lin T, Hutchison TL, Montgomery JA, Kellog DL, Babu YS (2001) Comparison of the anti-influenza virus activity of RWJ-270201 with those of oseltamivir and zanamivir. Antimicrob Agents Chemother 45 1162-1167... 

Chand P, Babu YS, Bantia S, Rowland S, Dehghani A, Kotian PL, Hutchison TL, Ali S, BrouUlette W, El-Kattan Y, Lin T-H (2004) Syntheses and neuraminidase inhibitory activity of multisubstituted cyclopentane amide derivatives. J Med Chem 47 1919-1929 Chand P, Bantia S, Kotian PL, El-Kattan Y, Lin T-H, Babu YS (2005a) Comparison of the antiinfluenza virus activity of cyclopentane derivatives with oseltamivir and zanamivir in vivo. Bioorg Med Chem 13 4071 077... 

Influenza viruses A and B can cause pneumonia in pediatric and adult patients. Amantidine and rimantidine are available oral agents with activity against influenza virus type A. If started within 48 hours of the onset of the first symptoms, they reduce the duration of the illness by about 1.3 days. Oseltamivir and zanamivir also are oral agents and are active against both type A and B viruses. These agents also reduce the duration of the illness by about 1.3 days if initiated within 40 to 48 hours of the first symptoms.29 For active infection beyond the first 48 hours, none of these agents is effective in treating the infection, and supportive care is the best treatment for these patients. 

The two classes of antiviral drugs available for treatment of influenza are the same as those available for prophylaxis and include the adamantanes, amantadine and rimantadine, and the neuraminidase inhibitors, oseltamivir and zanamivir. Because of widespread resistance to the adamantanes among influenza A viruses in the United States, amantadine and rimantadine are not recommended for treatment of influenza until susceptibility can be reestablished. 

Oseltamivir and zanamivir are neuraminidase inhibitors that have activity against both influenza A and influenza B viruses. When administered within 48 hours of the onset of illness, oseltamivir and zanamivir may reduce the duration of illness by approximately 1 day versus placebo. 

Currently, two classes of drugs are available with antiviral activity against influenza viruses inhibitors of the ion channel activity of the M2 membrane protein, amantadine and rimantadine, and the neuraminidase inhibitors oseltamivir, and zanamivir. H5N1 viruses isolated from poultry and humans in Thailand and Viet Nam in 2004 invariably showed an amantadine-resistance indicating that amantadine treatment is not an option during the ongoing outb-treak in South-East Asia. 

Oseltamivir and zanamivir are neuraminidase inhibitors that have activity against both influenza A and influenza B viruses. When administered within 48 hours of the onset of illness, oseltamivir and zanamivir may reduce the duration of illness by approximately 1 day versus placebo. Oseltamivir is approved for treatment in those older than the age of 1 year, while zanamivir is approved for treatment in those older than the age of 7 years. The recommended dosages vary by agent and age (see Table 41-3), and the recommended duration of treatment for both agents is 5 days. The FDA has received 103 reports, occurring between August 29,2005, and July 6,2006, of delirium, hallucinations, and self-injury in pediatric patients (mostly from Japan) following treatment with oseltamivir. 

Two agents, oseltamivir and zanamivir, are approved for the management of Influenza A and B infection. Both are potent neuraminidase inhibitors responsible for inhibiting viral replication. These agents differ in their structural compounds, enabling oseltamavir to have greater bioavailabihty and be the only oral option. There have been no reports of nephrotoxicity with the use of either agent. 

Prophylaxis vaccination is recommended for high-risk groups and all persons over 65 years. Oseltamivir and zanamivir may be used for postexposure prophylaxis and treatment under certain conditions (see National Institute for Clinical Excellence guidance in British National Formulary). 

Oseltamivir and zanamivir are available for treatment of infections due to influenza A and... 

Answer D. Neuraminidase is an enzyme on the lipid envelope of influenza A and B virions that prevents their clumping together and also their binding to the surface of cells that have been already infected. Neuraminidase inhibitors interfere with this activity and reduce the availability of virions for entry into noninfected cells. Oseltamivir and zanamivir decrease the severity and duration of symptoms if given within a day or two of onset... 

Oseltamivir and zanamivir are available for treatment of infections due to influenza A and B. The mechanism of their antiviral action is inhibition of which of the following ... 

Oseltamivir and zanamivir (not listed) are inhibitors of neuraminidase produced by influenza A and B. They prevent the trimming of sialic acid residues from viral proteins, facilitating their clumping and adhesion to host cells that are already infected. The answer is (C). 

K. Hata, K. Koseki, K. Yamaguchi, S. Moriya, Y. Suzuki, S. Yingsakmongkon, G. Hirai, M. Sodeoka, M. von Itzstein, and T. Miyagi, Limited inhibitory effects of oseltamivir and zanamivir on human sialidases, Antimicrob. Agents Chemother, 52 (2008) 3484-3491. 

M., and Miyagi, T. (2008) Limited inhibitory effects of oseltamivir and zanamivir on human sialidases. 

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