Describe the pharmacological basis of the management of organophosphate poisoning.

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College Answer

Organophosphates (OGP) bind irreversibly to acetyl cholinesterase. They produce a
cholinergic crisis and muscle paralysis due to excess Acetyl choline (ACh) at all muscarinic
and nicotinic receptors.
Candidates were required to discuss the pharmacology relevant to treating OGP poisoning,
including active decontamination/staff protection due to high lipid solubility, use of
antimuscarinics with central and peripheral action to treat cholinergic symptoms, supportive
therapy for muscle weakness (there is no antinicotinic agent available which does not
exacerbate muscle weakness), and finally the use of the cholinesterase regenerator, Pralidoxime, which may prevent the OGP-AChE complex ageing and becoming an irreversible bond if given in a timely fashion.
Good answers included a discussion of the mechanism of action of the therapeutic agents, the
time course of therapy, the large doses/infusions of atropine required and the titration of
therapy to reversal of muscarinic effects. Long lists of signs and symptoms were not required
to pass this question.
Syllabus H2b2c
Reference: Rang Dale Ritter 6th edition p 164-166
Katzung 10th edition p 116-117, 968.