Archive for the ‘side effects’ Category

Adverse drug reactions

April 30, 2007

I wrote awhile ago about idiosyncratic reactions and the challenge they pose to drug researchers. Perhaps one of the biggest challenges which is some ways might be considered a blessing is that, thanks to extensive pre-clinical testing and rigid regulatory standards, the number of incidences of adverse drug reactions is very low making it difficult to develop a sufficient body of data to determine the mechanism of the reaction. However, at this point in time, we have methods for investigating the genetic profile of patients and thus the potential exists to correlate adverse reactions with a genetic signature, but only if we have enough patients to work with.

A commentary in the April 26th issue of Nature describes a potential solution to the problem of lack of data….increasing the rate of adverse event reporting and pooling the data in a global database.

And now for something completely different…..

For anyone out there who teaches first year organic chemistry…the discussion by Euripides G. Stephanou of the paper published by Williams et al., which describes the chiral make-up of compounds released from forests into the atmosphere might make an interesting side bar example when the subject of stereoisomers is introduced.



April 5, 2007

Tamiflu, the anti-influenza neuraminidase inhibitor, discovered by Gilead and marketed by Roche has been taking a beating lately. In Japan over 1000 adverse events have been reported in the less than 6 years since the time it became available. The interesting thing is that 128 of these reports suggest some type of CNS toxicity mainly involving apparent highly reckless behaviour…attempting to jump off buildings or running in front of moving cars.

In addition, Tamiflu-resistant virus is popping up, even in people who have never taken the drug. At this point it doesn’t appear to be a problem, since most people can handle the flu, regardless of its resistance profile to this drug. The real danger would be if this scenario repeats itself during an outbreak of a more lethal strain, such as the H5N1 virus. Nonetheless, it’s likely that this situation can be reversed if doctors and patients are more vigilant in prescribing and taking the drug, respectively.

With regards to the side effect issue, it would be interesting to see if Glaxo’s neuramindiase inhibitor Zanamir, causes the same problems. I suspect it won’t since unlike Tamiflu, which is an oral drug, Zanamivir is poorly absorbed and thus must be given by inhalation where only 4 to 17% of the drug is systemically absorbed. When talking about treating the flu, this is fine because the virus is located in the respiratory tract. Therefore, if it turns our that the Tamiflu side-effects are caused by the drug and that they are related to the drug’s mechanism, Zanamivir could offer a safer alternative since there would be less systemic exposure.