Introduction - Uppsala Monitoring Centre

committees to assess a specific ADR problem.
Health Insurance schemes
The end of the nineteenth century saw the realisation that a form of national
insurance against the vicissitudes of life would spread the burden more equally.
Various mutual benefit clubs had started in the 18 th century. One for seamen who
had to pay sixpence a month towards the seamen’s hospitals for decayed seamen,
their widows and children was ordained by an Act of Parliament in 1696. The benefit
clubs paid doctors out of weekly contributions made by members. The club
managers usually paid the doctors on the basis of an amount per member, i.e. a
capitation fee. The first national insurance scheme was in Germany and was started
by Bismark in 1883. The British scheme started in 1911 by the National Insurance
Act of 1908. Where drugs were paid for by a scheme there was strict supervision to
make sure money wasn’t wasted by giving expensive medicines. This meant that
more people were able to benefit from drugs and that there was enough supervision
to prevent the prescribing of quack medicines.
Interactions
I have found no mention of any interaction between herbs other than the references
from Galen in c150 AD and the Chinese in 220 AD that toxicity can be reduced by
adding another herb. In 1667 George Castle says ‘The mixing of things which are
harmless sometimes produces a poison’; but this refers more to chemical
interactions. The lack of references to interactions may be because there were few
herbs with active principles and, therefore, few interactions. There are some herbs
that contain more than one active principle and there is the possibility that these
interact and it has been suggested that two of the digoxin glycosides, digitoxin and
verodoxin, interact so that the action of digitoxin is enhanced, but I can find no
evidence to support this. This situation has been called ‘The SEES 164 theory’
(Sutrisno, 1978). It must, however, have been obvious that herbs with similar
properties should not be combined, e.g. belladonna, henbane and mandrake, which
all contain tropane alkaloids, i.e. pharmacodynamic interactions should have been
recognised. Pharmacokinetic interactions would have been more difficult to
appreciate and may have been even rarer. St John’s Wort is known to affect CYP
1A2 165 , 2C9 and 3A4 and thereby increases the metabolism of digoxin so that on
stopping the St John’s Wort the concentration of digoxin rises and may cause an
ADR. The stopping of the St John’s Wort may have occurred long after the starting
of the digoxin so that the ADR would not appear to have been caused by the
164 SEES = Side Effects Eliminating Substances or Secondary Effective Eliminating Substances
165 CYP = isoenzymes of cytochrome P450