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The kinetic basis of organophosphate poisoning and its treatment

Authors
  • Green, A.L.
Type
Published Article
Journal
Biochemical Pharmacology
Publisher
Elsevier
Publication Date
Jan 01, 1958
Volume
1
Issue
2
Pages
115–128
Identifiers
DOI: 10.1016/0006-2952(58)90019-4
Source
Elsevier
License
Unknown

Abstract

The biochemical lesion in organophosphate poisoning is inhibition of cholinesterase which results in auto-intoxication by accumulated acetylcholine. Possible therapeutic processes are antagonism of acetylcholine, direct detoxication of the organophosphate, or reactivation of the inhibited enzyme. In this paper a simple mathematical model of the physiology of poisoning and treatment has been constructed by kinetic analysis of the basic biochemical reactions involved in these processes, with the added assumption that an animal will die once the fraction of cholinesterase in its body has fallen below an arbitrary minimum. Formulae have been derived from the model which enable the therapeutic efficiencies of the different forms of treatment, either alone or in combination, to be calculated. Qualitatively, the experimental and calculated relative efficiencies of the different therapeutic processes are in good agreement.

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