Take Two Aspirin?

October 3, 2009

As you all know, there has been a great deal of media coverage of the emergence of the H1N1 influenza virus (“swine flu”).   There is some evidence that with this virus, unlike the normal seasonal flu, younger people may be more at risk than those over 50.  This in turn has prompted people to draw parallels with the 1918-1919 influenza pandemic (the “Spanish flu”), which also affected young people more severely, and which killed at least 20 million people.

There is an interesting, and slightly disturbing, article on the PhysOrg.com site, reporting on a new study [abstract] that suggests that one of the factors that may have influenced the course of the 1918-19 epidemic was the (over)use of aspirin.

High aspirin dosing levels used to treat patients during the 1918-1919 pandemic are now known to cause, in some cases, toxicity and a dangerous build up of fluid in the lungs, which may have contributed to the incidence and severity of symptoms, bacterial infections, and mortality

Although aspirin was widely used and promoted for the treatment of flu, its mode of action and pharmacology were poorly understood.  (Indeed, the mechanism by which it works, inhibition of the production of prostaglandins and thromboxanes, via inactivation of the enzyme cyclooxygenase, was not discovered until 1971.  Sir John Vane, then of the Royal College of Surgeons, was knighted and received the 1982 Nobel prize in Medicine for this work.)    Nonetheless, very large doses of aspirin (ranging from 8 to 31 grams per day) were commonly given to flu patients.  From the abstract:

The hypothesis presented herein is that aspirin contributed to the incidence and severity of viral pathology, bacterial infection, and death, because physicians of the day were unaware that the regimens (8.0–31.2 g per day) produce levels associated with hyperventilation and pulmonary edema in 33% and 3% of recipients, respectively.

By way of comparison, the usual over-the-counter dose of aspirin for adults is two 325 mg tablets, or 650 mg, every 4-6 hours, corresponding to 3.9 grams per day at the maximum dosing frequency.

We now know, of course, that aspirin does have potentially bad side effects, including gastrointestinal irritation and bleeding, in addition to those noted in the study.   And this study will need to be confirmed (or not) by further research.  It is a useful reminder, though, that new “breakthroughs” are not always quite what they seem, and that some caution is in order.

There is another, slightly earlier,  example of a poorly-understood new drug that should also urge us to some caution.  First synthesized in 1874 at St. Mary’s Hospital, London, and later independently synthesized in 1897 by a predecessor company of what is now Bayer AG, diacetyl morphine was marketed from 1898 through 1910 as a cough suppressant and non-addictive substitute for morphine.  Subsequent events proved this view a little too rosy, and it is not sold today, at least legally.  You have probably heard of it under its original trade name: heroin.

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