Introduction - Uppsala Monitoring Centre

illustrating that tolerance to some drugs occurs. The idea of titrating the dose until
there was a satisfactory conclusion might seem admirable but in some cases the
appearance of side effects was linked to a ‘satisfactory’ dose, e.g. salivation washed
out the evil of syphilis and Withering said that at first he thought it was necessary to
bring on sickness to ensure that digitalis produced the correct diuretic effect. Quinine
dosage was increased until there was singing in the ears. It was suggested that the
dose of salicylate in rheumatism should be increased daily, or every second day,
until any unpleasant side-effect, such as vomiting, deafness, tinnitus or a tendency
to delirium is observed (Lees, 1909). Colchicum must be increased in dosage until
bowel action confirms that it has reached the correct level (Christison ,1858). The
principle of increasing the dosage until an adverse reaction occurred must have
been common with drugs/herbs with a low therapeutic index. Even now the idea that
side effects indicate that a drug is working correctly lingers on.
We have seen that ever since 865 AD rulers have fought against adulteration
and still do so today. The apothecaries added their voice. Healers tended to work
alone only joining together as a trade union when their livelihood was threatened by
competition from quacks selling cheaper adulterated drugs. In 1316 The Guild of
Pepperers wrote a code for quality control and 10 years later in 1332 the College of
Medicine of Paris made certain that all apothecaries had a standard textbook. A
hundred years later, in 1423 the Commonality of Physicians and Surgeons of
London are inspecting the wares in apothecaries’ shops. In 1540 King Henry VIII
appointed four inspectors of apothecaries’ wares, drugs and stuffs. One of the
earliest examples of a drug being taken off the market because of an ADR was
when a University faculty, the Paris Faculty of Physicians, in 1566 forbade the sale
of antimony because it was a dangerous poison that should not be taken internally.
In 1747 the Apothecaries of the Cities of London and Westminster petitioned the
English House of Commons to strengthen the law against practitioners dispensing
drugs of dubious quality; an early example of the pharmaceutical industry trying to
influence the government. A paper in 1779 on ‘Quackery, and the most effectual
means of checking its dangerous progress’ suggested having a public board to
judge new drugs before being allowed to be sold or advertised; the first step towards
having a committee for the safety of medicines. About the same time in France,
1778, the Société Royale de Médicine became the only competent authority for the
authorisation of new drugs. This would seem to be the first example of the licensing
of drugs. The medical societies became interested in the serious ADRs and in 1832
the Royal Medical and Chirurgical Society set up a committee to enquire into the
problems with chloroform, but it wasn’t until 1877 that the BMA put this into action
and it was 1880 before the McKendrick report was published. In 1914 in the UK
there was a recommendation that all medicines should be registered after
considering their quality, safety and efficacy; but the publication coincided with
outbreak of the First World War and it was shelved. In the US a bill to expand