Anticholinesterases cholinesterase poisoning

Presently available methods to diagnose and biomonitor exposure to anticholinesterases, e.g., nerve agents, rely mostly on measurement of residual enzyme activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in blood. More specific methods involve analysis of the intact poison or its degradation products in blood and/or urine. These approaches have serious drawbacks. Measurement of cholinesterase inhibition in blood does not identify the anticholinesterase and does not provide reliable evidence for exposure at inhibition levels less than 20 %. The intact poison and its degradation products can only be measured shortly after exposure. Moreover, the degradation products of pesticides may enter the body as such upon ingestion of food products containing these products. 

As stated previously (pp. 62 etseq.) there is often correlation between anticholinesterase activity in vitro and gross mammalian toxicity. The toxicity of O.M.P.A. is not very muoh less than that of tabun, D.F.P. and T.E.P.P., yet the anti-cholinesterase activity of O.M.P.A. in vitro is negligible (50 per cent inhibition, 4-5x10 2m). On the other hand, O.M.P.A. produces all the symptoms of acetylcholine poisoning when administered to animals. Moreover, the serum cholinesterase of such animals is almost completely inhibited. Another anomaly of O.M.P.A. is that toxic action is slower than that of D.F.P. or tabun, an hour s delay being usual compared to the very quick knock-out action of D.F.P., etc. (see p. 2). 

Mechanism of Action Reactivates cholinesterase activity by 2 formyl l methylpyri dinium ion. Therapeutic Effect Restores cholinesterase activity following organo-phosphate anticholinesterase poisoning. 

Stansley, W. Field results using cholinesterase reactivation techniques to diagnose acute anticholinesterase poisoning in birds and fish. Arch. Environ. Contam. Toxicol. 25 315-321, 1993. 

Askew, B.M. (1956). Oximes and hydroxamic acids as antidotes in anticholinesterase poisoning. Br. J. Pharmacol. 11 417-23. Augustinsson, K-B. (1948). Cholinesterases a study in comparative azymo o. Acta Physiol. Scand. 15 (Suppl. 52) 1-182. Augustinsson, K-B. (1959). Electrophoresis studies on blood plasma esterases I. Mammalian plasmata. Acta Chem. Scand. 13 571-92. 

Anticholinergic agents are typically used as treatment for anticholinesterase poisoning and vice versa. Riysostlgmlne, tetrahydroamlnoacrldlne, and other cholinesterase Inhibitors were used successfully as antidotes In several dozen subjects. The demonstration of physosclgmlne s effectiveness led to the first controlled study of Its ability to reverse delirium due to scopolamine (31). Riysosclgmlne has been used to overcome anticholinergic toxicity. 

Anticholinesterases are agents that inhibit the enzyme acetylcholinesterase (AChE) and other cholinesterases that degrade acetylcholine (ACh). The hrst known anticholinesterase agent was Calabar bean, known as ordeal poison or ordeal bean its active ingredient is the carbamate compound physostigmine (Koelle 1975). It is thought that the Calabar bean was used by native tribesmen of Western Africa who used it in witchcraft rituals. The principle behind its use was that if a tribal member was accused of a capital crime, he or she would be subjected to a trial by ordeal in which they were forced to eat Calabar beans. If a person was innocent, he or she would quickly eat the beans with little apprehension, which would quickly induce... 

Poisoned patients may require monitoring of vital signs, measurement of ventilatory adequacy such as blood gases and pulse oximetry, leukocyte count with differential to assess development of pneumonia, and chest radiographs to assess the degree of pulmonary edema or development of hydrocarbon pneumonitis. Workers involved in the formulation and application of pesticides should be monitored by periodic measurement of cholinesterase activity in their bloodstream. Untreated, anticholinesterase-depressed acetylcholinesterase activity returns to normal values in approximately 120 days. 

Marrs TC and Bright JE (1992). Histochemical localization of cholinesterase in anticholinesterase poisoning. In Clinical and Experimental Toxicology of Organophosphates and Carbamates (B Ballan-tyne and TC Marrs, eds), pp. 28 13. Oxford, UK Butterworth-Heinemann. 

Barckow D, Neuhaus G and Erdmann WD (1969). Zur Behandlung der schweren Parathion - (E 605) - Vergiftung mit dem Cholinesterase-Reaktivator Obidoxim (Toxogonin). Arch Toxicol, 24,133-146. Barr MA (1964). Poisoning by anticholinesterase organic phosphates it significance in anaesthesia. MedJAust, 00, 792-796. 

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). 

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