Observations on experimental and human paracetamol overdosage
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Dixon, Michael F.
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Abstract
This thesis records my investigations into the
consequences of overdosage with the analgesic drug
paracetamol. The major complication, that of hepatic
necrosis, has been investigated in experimental animals
using light-microscopy, electron-microscopy and histo¬
chemistry. The pathological findings in 18 fatal human
cases are recorded and compared and contrasted with
previous reports in the literature. A further 16
fatalities resulting from overdosage with compound
preparations containing paracetamol are also reported.
A variety of methods for quantifying the extent of
hepatic necrosis have been evaluated, including the use
of the image-analysis computer, and these methods
applied to experimental and human material.
In addition to morphological studies, the
influence of microsomal induction on the toxic meta¬
bolism of the drug has been investigated and the
effectiveness of a possible antidote, a-tocopherol,
has been tested in the rat.
The thesis includes chapters on the history and
usage of paracetamol and on the treatment of overdosage
based on reviews of the literature.