11. Drugs to treat influenza:
The main form of treatment is prevention, in the form of vaccines. The currently available vaccines are based on killed virus, and induce an immune response (mainly Ab response) to the hemagglutinin and neurimidase proteins. While the vaccines are relatively efficacious towards the virus strain/s on which they are based, the immunity they induce is short-lived and they quickly become obsolete due to the antigenic drift of the influenza virus. Newer types of vaccines include: cold-adapted attenuated live virus vaccines and “subunit” vaccines, consisting of virus proteins/peptides produced by recombinant DNA technology.
While everyone can have a bad dose of the ‘flu’, persons who are particularly at risk and should get vaccinated are diabetics, severe asthmatics, persons with heart disease/chronic lung disease, children with cyanotic congenital heart disease, persons undergoing immune-suppressive therapies and those over 65 years of age.
Various treatments are available, from the time-proven ones (rest, hydration and acetaminophen) to various antiviral agents (ribavirin and rimantadine). Ribavirin is a purine nucleoside analog with relatively broad antiviral spectrum in cell culture. It inhibits some DNA viruses and many RNA viruses, including Influenza A and B viruses, as it appears to inhibit virus replication by several different mechanisms, perhaps explaining its range of activity. The triphosphate form of ribavirin inhibits virus encoded, DNA-dependent DNA polymerases and possibly RNA-dependent RNA polymerases as well. Ribavirin monophosphate inhibits inosine monophosphate dehydrogenase, leading to an overall reduction in cellular pools of GTP, which in turn resistricts viral (and cellular) nucleic acid synthesis. In addition it impairs capping of virus-specific messenger RNA (by the addition of methylated guanine nucleotides to the 5’ end of RNA molecules). The relatively broad spectrum of ribavirin is accompanied by a concomitant lack of potency at nontoxic doses, probably because the mechanisms by which it inhibits viruses are nonspecific and also inhibit cellular enzymes. Lack of specificity translates into poor clinical activity for most viral infections.
The anti-influenza drugs Amantadine and Rimantadine target the entry of the influenza virus into host cells, specifically the A strain. The primary mechanism of action involves disrupting virus entry by preventing virion disassembly. The influenza A virion contains a transmembrane protein M2, that is well conserved among human and avian strains. The M2 protein functions as an H+ ion channel. Influenza virus enters cells through endosomes, and the M2 protein allows H+ ions to move from endosomes into the virion interior during the entry process. The flux of H+ ions decreases the pH in the virion, which is necessary for conformational changes in the influenza virus nucleocapsid protein that allow movement of the viral ribonucleoproteins (containing the viral genome segments) into the cell nucleus to establish infection. Amantadine and Rimantadine inhibit the ion channel function of M2, presumably by their large structures blocking the channel through which the ions flow. They effect impedes influenza virion disassembly after internalization through endosomes. Resistance to Amantadine and Rimantadine occurs with a single amino acid substitutions at particular points in the transmembrane region of M2 that prevent drug binding within the channel. When treatment is initiated before exposure to the virus, the drugs prevent clinical disease in more than 75% of cases. About 3-5% of amantadine recipients report mild CNS reactions, including anxiety, insomnia, and difficulty concentrating. The main use has been prophylaxis in individuals who are at increased risk of severe infection during suspected influenza A virus epidemics. A major limitation of the drugs is that they are not active against influenza B strains; drug disruption of M2 function is specific for influenza A strains.
1 comment:
I should ask - while the exact mechanism of many of these drugs to prevent influenza is important to understand we're missing out on the bigger picture. perhaps it's important to address what age groups are particularly affected by influenza. I know for a fact that we typically immunize the elderly, however new strains of influenza are begining to affect the younger populations... So what does this mean? Should we start vaccinating among the younger populations as well?
None of the responses so far have hinted at the fact that each year we must develop a new vaccine; which is pretty much a guess of what the next mutagenic strain will become on the condition that antigenic drift is all that play a part in the viral evolution. In 2004 we had a massive vaccine shortage due to the fact that the vaccine produced in Australia was ineffective and even considered dangerous against the strain that became prevalent.
Will current vaccines and vaccine development be enough to prevent an outbreak on the same scale as the Spanish Flu (I think it was the H1N1 derivative)?
So, if you've got influenza how does it kill and are there thearapies that will improve your chances at recovery. Victims of the spanish flu included a notable number of children and infants. Research conducted on lab animals concluded that these victims may have died from a 'cytokine storm'... Therefore an effective treatment for these cases could have been some treatment to downregulate the immune response before it gets out of hand.
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