Introduction - Uppsala Monitoring Centre

Ideal knowledge of an ADR
How much do we know about the most common reactions for the first five marker
drugs compared with a modern drug–Streptomycin (Type A reaction characteristics
in italics that will alter with dose):
The manifestation (clinical or laboratory) both subjective and objective.
Graded both for severity and seriousness
Frequency or incidence, both absolute and relative to similar drugs with
confidence intervals.
Mechanism of action.
Causality
Predisposing factors.
Treatment and its effect
Reversibility or sequelae.
Next we will look at the dates of the first reports of the adverse events for the four
ancient marker drugs: hellebore, henbane, and mercury and opium.
The dates of the first reports on the adverse events with a marker drug
tell us how quickly the new AEs were discovered and reported. Table 12
covers the four ancient drugs and shows that after an active Greek and
Roman period there was a relative dark age for drug safety in the Western
world from the 2 nd century until the 16 th century, whilst there was an active
Arabic period in the 9 th century. The birth of printing followed by the
introduction of medical journals seem to have spurred another active period
in the West from the 16 th to the 20 th century. The relative inactivity thereafter
probably reflects the disuse of these drugs as the active principles of
henbane and opium took over from the raw herbs and the uselessness of
hellebore was realised in the late 19 th century and better drugs supplanted
mercury. The peak for mercury in the 16 th century was caused by the syphilis
epidemic in combination with the newly started printing presses. The 18 th
century was the start of the period of medical experimentation when
reporting new adverse events reached its peak. Hahnemann’s provings after
1810 produced a plethora of possible adverse reactions for hellebore, but
apart from this there was a decline in new reports during this century. These
data are very soft as they depend on the depth of my research, the
availability of original reports, and the relative inaccessibility of reports in
foreign languages.