What is the primary mechanism of action in the pathophysiology of organophosphate (OP) toxicity?

Updated: Sep 22, 2018
  • Author: Kenneth D Katz, MD, FAAEM, ABMT; Chief Editor: Sage W Wiener, MD  more...
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Answer

The primary mechanism of action of organophosphate pesticides is inhibition of carboxyl ester hydrolases, particularly acetylcholinesterase (AChE). AChE is an enzyme that degrades the neurotransmitter acetylcholine (ACh) into choline and acetic acid. ACh is found in the central and peripheral nervous system, neuromuscular junctions, and red blood cells (RBCs).

Organophosphates inactivate AChE by phosphorylating the serine hydroxyl group located at the active site of AChE. Over a period of time, phosphorylation is followed by loss of an organophosphate leaving group and the bond with AChE becomes irreversible, a process known as aging.

Once AChE has been inactivated, ACh accumulates throughout the nervous system, resulting in overstimulation of muscarinic and nicotinic receptors. Clinical effects are manifested via activation of the autonomic and central nervous systems and at nicotinic receptors on skeletal muscle.


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