Introduction - Uppsala Monitoring Centre

Douthwaite and Lintott first showed bleeding from the stomach via a gastroscope in
1938. The semi-flexible gastroscope only having been invented in 1932 (Douthwaite
and Lintott, 1938).
The terminology in the 1900s was not as specific as that used in the present
century, e.g. agranulocytosis was first described in 1922 as angina agranulocytotics
(Hess et al., 1983), although aplastic anaemia was described as early as 1888 by
Erlich (Erlich, 1888). Many of the early reports were couched in terms of symptoms
such as dimness of vision, albuminuria and rashes, which were later, specified as
individual specific disorders.
In the various listings it is difficult to separate the ADRs occurring at normal
therapeutic doses from those where an overdose has taken place due to large
variations in individual responses.
The sources for 2006 and 2007 (Meyler’s, Micromedex, Inchem and Martindale’s)
do not mention peritoneal irritation, diarrhoea, vertigo, cardiac insufficiency,
bradycardia, insomnia, agitation, dysarthria, polyuria, Cushing’s syndrome, haematuria,
megaloblastic anaemia, alopecia or conjunctivitis. Although 11 of these were
mentioned in earlier Meyler’s. In all I have traced 65 adverse events: Meyler’s; prior to
2006; mentioned 56; Meyler’s 2006–40; Martindale 2007–28; Inchem 2007–40. There
are probably several reasons why they have not included all of them: too rare, doubtful
ADR or dealt with under a broader term.
In planning any pharmacovigilance with a new drug one needs to examine the
prior probabilities, which will be partly based on drugs of the same class, i.e. other
salicylates. How soon were the predictable ADRs recognised with Aspirin?
I contacted Bayer Archives with a view to obtaining more information about
Aspirin ADRs, but I was unsuccessful.
Relating serum salicylate concentration to symptoms
For treatment of acute rheumatic fever the maintenance level should be 30–35
mg. per 100cc. (Hoffman et al., 1949). The Mayo clinic considers the optimum
level for rheumatoid arthritis to be 18–20 mg per 100cc., but may need from 60–
125 grains (3.9 to 8.1 gm) a day (Greer et al., 1965). A single dose of Aspirin of
2 gm. gave levels of 10 mg. per 100cc. A dose of 12 to 20 gr. (0.8 to 1.3 gm)
every four hours until the desired level had been reached and then the same
dose every six hours maintained levels of between 20 and 25 mg. per 100cc.
(Hoffman et al., 1949). The toxic dose of sodium salicylate is between 12 and 30
gr (0.78 gm to 1.95 gm) in a single dose (Duchesney, 1954).