Humans anticholinesterase poisoning

Abbara et al. performed simultaneous quantification of different antidotes (diazepam, pralidoxime and atropine) typically co-administered for the therapy of anticholinesterase poisoning (Table 5) [44], PK data resulting from i.m. drug injection by means of a bi-compartemental auto-injector were calculated from human plasma concentrations measured by LC-ESIMS/MS with MRM settings. Administration of 2 mg atropine sulphate yielded plasma peak concentrations of about 4 ng/ml 15 min after injection. 

Toxification rates may vary. For example, when humans are acutely poisoned by the systemic insecticide menazon, there is an incubation period (of up to one day) and a slow growth in the anticholinesterase activity when the PS-form with low toxicity becomes the active PO-form [A17]. 

Organophosphates. The acute toxicity of organophosphate pesticides is basically derived from the anticholinesterase property of these chemicals. This property, which results in accumulation of acetylcholine at synapses and myoneural junctions, is responsible for both the insecticidal activity and mammalian toxicity. Early symptoms of organophosphate poisoning in humans include, among others, miosis (pinpoint pupils) and blurred vision, and a response known as the SLUD (salivation, lacrimation, urination, and diarrhea) syndrome all of these are the result of muscarinic effects (12-15). Clinical manifestations of more severe poisoning involve predominantly nicotinic and central effects which include convulsions, paralysis, depressed respiration and cardiovascular functions, and coma (12-15). Death is usually due to respiratory failure, accompanied by cardio-vascular failure (13). 

If rats, during a brief hexobarbitone anaesthesia, are intravenously injected with barely sublethal doses of organo-phosphorus cholinesterase inhibitors which are able to pass the blood-brain barrier, the animals produce a hypothermia of 4-6° in 2-3 h, followed by spontaneous recovery in 12-20 h. This phenomenon has also been demonstrated in mice but not in guinea pig or rabbit. A few clinical reports of human cases of organo-phosphate poisoning mention a severe drop in the body temperature of the victims. The anticholinesterase hypothermia in the rat can partly be prevented by systemic atropine, but not by atropine methyl nitrate (for details and references, see Meeter, 1971a). 

OPIDN is thought to be mediated by OP acting not as an anticholinesterase but as a neurotoxic esterase. The condition is not seen in poisonings by aU OP pesticides and has not yet been reported in humans exposed to nerve gases. 

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