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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

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November 21, 2005

Old Standbys

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Posted by Derek

I wanted to let everyone know that I have an article up on Medical Progress Today, wondering where all those safe drugs we grew up with have gone. . .you know, aspirin, acetominophen, penicillin, that sort of thing. . .

Comments (3) + TrackBacks (0) | Category: Toxicology


COMMENTS

1. milo on November 21, 2005 11:51 AM writes...

Nice piece.

So, is it realistic to demand that the drugs we take have no side effects? Sure, aspirin and acetominophen have side effects, but people still use them. I just wonder how many potentially good pharmaceuticals have been tossed because they "might" be risky, and what level of risk is acceptable?

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2. Daniel Newby on November 22, 2005 10:17 PM writes...

"Not sure exactly what is meant by, 'the half life of minutes makes the side effects of the parent compound very specific' ..."

Acetylsalicylate might very well push something important out of equilibrium, but most stuff in the body takes so long to adjust that the aspirin is long gone before it gets out of hand. Something dramatic* has to happen in that short window to see an effect.

*For instance, acetylating the active site of cyclooxygenases. A platelet lacks the machinery to build new proteins, so it loses the enzyme for good. Fortunately the stomach can restore its COXes rapidly, else aspirin would be horrifically dangerous.

Re. acetaminophen, it is underappreciated, but starvation, even short-term, depletes liver glutathione stores dramatically. I once read a case report of an underfed person with mild liver problems being killed by a single 4 gram dose. I handle it with kid gloves after reading that. It is unconscionable to adulterate narcotics, which cause tolerance with proper use, with such a substance.

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3. fletcher@speakeasy.org on November 25, 2005 12:31 AM writes...

Ah, gotcha. Yes, I totally agree -- very well put.

And I also totally agree about ruining perfectly good narcotics with that acetominophen stuff. Similar to the case report you mention, I read about a patient with nausea and vomiting from a bad cold who while only taking the prescribed doses of a few different cold medicines ended up dead of liver failure -- neither she nor the prescribing physician realized that a few of the different drugs had acetominophen in them, adding up to a toxic dose in someone not able to hold down food. Details vague as they taught us this one in 1st year pharmacology to drive home the point and I no longer recall the specifics. =(

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