Introduction - Uppsala Monitoring Centre

1. A greater awareness of risks of the medications, some of which were
established drugs for some time (debendox, phenformin and oxyphenbutazone).
2. A growing ability to study and characterize the risks of the agents
3. A growing risk averseness on the part of the media and consumer public
4. A lower threshold and/or facilitated means for regulatory action
5. A greater awareness and reporting of events relating to health risk, including
adverse effects of chemical and drugs, in the media (Jones, 1990)
Until the mid-nineteenth century herbs, whose adverse effects had been known
for centuries, gave way to the synthetic drugs as the main armamentarium of the
prescriber and with this flood of new drugs came their new problems. The response
was slow but steady until an acceleration of new drugs in the 1950s when
thalidomide arrived and pharmacovigilance changed forever.
Part 4. Discussion
The development of the pharmacovigilance process
It seems that every substance on this planet has been used as a medicine at some
time and in some place and the results depended largely on how much they took of
each substance. We have to presume that the earliest humans could distinguish
between poisonous and non-poisonous berries, etc. and were aware that, in the
majority of cases, the amount that they took of them influenced the results. i.e. they
knew of type A reactions. The first published evidence that they also knew of type B
reactions was in 49 BC when Titus Lucretius Carus wrote ‘ What is food to one to
some becomes fierce poison.’. This was explained in 1657 by Culpepper and his
colleagues ‘One and the same plant, is sometimes salutary to one man but noxious
and death to another, by reason of the peculiar constitution of the individuum’ and 8
years later by Nedham ‘The very same remedy which saved a man’s life to-day may
in the same disease, at a different time, kill another tomorrow.’ This adds the sense
of personal idiosyncrasy, rather than that it is a fault of the dose of the drug. It wasn’t
until 1786 that Leigh gave a healthy volunteer increasing doses of a drug and notes
the increasing severity of the reaction and then 7 years later a self-experimenter
Crumpe records the results of a reaction every 5 minutes, thereby giving a temporal
dimension to the reaction. Self-experimentation was first recorded as occurring in
2500 BC when Emperor ShenNong was reputed to have tasted seventy kinds of
toxic substances in a single day. No doubt many healers followed and still follow his
example, but did not record their results. However, common sense must have
caused them to try drugs in animals before using them in man and Rhazes in 865
AD tried proposed remedies first in animals. In 1680 Wepfer added a moral twist by
saying ‘My sin will be less, if I explore the effects of poison in animals in order to be