Aetiology
Organophosphates are used as pesticides in a wide range of settings including agricultural spraying, domestic baits and sprays, termite treatments, and lice and tick products.
They may also be used as chemical weapon nerve agents; however, these are different from pesticides in that they have been specifically selected for their unfavourable characteristics (i.e., relatively high toxicity to humans, high potency, rapid onset of action, high volatility, good absorption via dermal or inhalation exposures, and resistance to antidote effects).
Pathophysiology
The primary mode of action of organophosphates is to inhibit neuronal acetylcholinesterase (AChE). This leads to excessive acetylcholine at sympathetic, parasympathetic, central nervous system (CNS), and neuromuscular junction sites. Parasympathetic effects are predominant early on in most poisonings, causing excessive secretions, bronchospasm, diarrhoea, and pinpoint pupils. Sympathetic effects may lead to hypertension and tachycardia. CNS cholinergic effects are important in severe poisonings, as they contribute to seizures and respiratory failure. Neuromuscular junction stimulation leads to early fasciculations and may lead to weakness that persists for days to weeks beyond the other features. Delayed-onset CNS and peripheral (predominantly motor) neuropathy are uncommon, but may be severe and can lead to permanent disability. Underlying mechanisms and susceptibility are poorly understood.[3]
Esterases (such as acetylcholinesterase and neurotoxic target esterase) are inhibited by organophosphorus through phosphorylation. Inhibited acetylcholinesterase reactivates spontaneously at very slow rates; oximes speed up this reaction. However, phosphorylated acetylcholinesterase may lose an alkyl side chain non-enzymatically, leaving a hydroxyl group in its place (“ageing”). Regeneration is then no longer possible.
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