Cholinergic crisis acetylcholine accumulation

Excessive dosing with an anticholinesterase can actually worsen the muscle weakness in myasthenics if the accumulation of acetylcholine at the neuromuscular junction is sufficient to cause depolarising blockade cholinergic crisis). It is important to distinguish this type of muscle weakness from an exacerbation of the disease itself myasthenic crisis). The dilemma can be resolved with a test dose of edrophonium, which relieves a myasthenic crisis but worsens a cholinergic one. The latter may be severe enough to precipitate respiratory failure and should be attempted only with full resuscitation facilities, including mechanical ventilation, at hand. 

IMS is clearly a separate clinical entity from acute cholinergic crisis and delayed neuropathy. The acute cholinergic crisis usually emerges within a few minutes to a few hours and is due to acetylcholinesterase (AChE) inhibition resulting in acetylcholine accumulation at the synapses in the nervous system and at the neuromuscular junctions. Patients acutely poisoned with OPs exhibit muscle fasciculations. 

The main toxic effect of the OPs is the inhibition of the acetylcholine esterase (AChE) in the synapses and neuromuscular junctions, causing cholinergic crisis, which eventually leads to seizures, respiratory arrest and death. There are considerable differences in the dynamic of clinical manifestations and impairment induced by nerve agents and OP insecticides (slower onset, dependent on metabolic activation, prolonged effect based on their accumulation in certain tissues and subsequent systemic release). 

The effect of OP/nerve agents is characterized by their interference with cholinergic nerve transmission via inhibition of AChE and BuChE. The cholinergic crisis (accumulation of neuromediator acetylcholine) is... 

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