Cholinesterase inhibitors central nervous system effects

Absorption of the quaternary carbamates from the conjunctiva, skin, and lungs is predictably poor, since their permanent charge renders them relatively insoluble in lipids. Thus, much larger doses are required for oral administration than for parenteral injection. Distribution into the central nervous system is negligible. Physostigmine, in contrast, is well absorbed from all sites and can be used topically in the eye (Table 7-4). It is distributed into the central nervous system and is more toxic than the more polar quaternary carbamates. The carbamates are relatively stable in aqueous solution but can be metabolized by nonspecific esterases in the body as well as by cholinesterase. However, the duration of their effect is determined chiefly by the stability of the inhibitor-enzyme complex (see Mechanism of Action, below), not by metabolism or excretion. 

The lack of classic muscarinic effects does not exelude the possibility of cholinesterase inhibitor poisoning in young children with central nervous system depression. In one ease series, tearing and diaphoresis were not observed in pediatrie patients (Lifshitz et al, 1999). Miosis was absent in a number of pediatric patient cases reported in the literature with 27% of children in one case series lacking miosis on admission (Zwiener and Ginsburg, 1988). The percentage was 20% in another case series of pediatric patients (Sofer et al, 1989). 

SAFETY PROFILE Poison by ingestion, inhalation, skin contact, intraperitoneal, intravenous, subcutaneous, and ocular routes. Human systemic effects by ingestion a cholinesterase inhibitor. Has been found to inhibit peripheral cholinesterase without pronounced effects on the central nervous system. An insecticide. When heated to decomposition it emits toxic fumes of NO and POx. See also PARATHION and ANHYDRIDES. 

Toxic action is complex, involving both stimulation and blockade of autonomic ganglia and skeletal muscle neuromuscular junctions, as well as direct effects on the central nervous system. Paralysis and vascular collapse are prominent features of acute poisoning, but death is usually due to respiratory paralysis, which may ensue promptly after the first symptoms of poisoning. Nicotine is not an inhibitor of cholinesterase enzyme. 

Beck, K. D., Brennan, F, X, Moldow, R. L Oiteitwcllcr, J, E., Zhu, G,. and Servatius, R. J. (2003). Stre-ss interacts with peripheral cholinesterase inhibitors to cause central nervous system effects. Life Sci. 73,41-51. 

Cholinesterase inhibitors have minimal effects by direct action on vascular smooth muscle because most vascular beds lack cholinergic innervation (coronary vasculature is an exception). At moderate doses, cholinesterase inhibitors cause an increase in systemic vascular resistance and blood pressure that is initiated at sympathetic ganglia in the case of quaternary nitrogen compounds and also at central sympathetic centers in the case of lipid-soluble agents. Atropine, acting in the central and peripheral nervous systems, can prevent the increase of blood pressure and the increased plasma norepinephrine. 

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