Observations on experimental and human paracetamol overdosage
Dixon, Michael F.
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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.