Cholinesterase inhibition: complexities in interpretation

Abstract

Abstract Cholinesterases are measured to assess exposures to or effects of organophosphorus esters and carbamates. Plasma butyrylcholinesterase is usually most sensitive to inhibitors, but it has no known physiological function(s); its inhibition reflects exposure. The physiological function of erythrocyte acetylcholinesterase (AChE) also is not known, but the enzyme is the same as that involved in synaptic transmission and its measurement is used to mirror effects on the nervous system. Erythrocyte AChE has large inter- and intraindividual variation, and small changes are detectable by comparison with preexposure values. The relation between inhibition of erythrocytes and nervous tissue AChE depends on the pharmacokinetics of inhibitors. Usually, erythrocyte AChE inhibition overestimates that in the nervous system. Pharmacodynamic factors such as spontaneous reactivation and aging of inhibited enzyme should also be considered in assessing AChE inhibition. Other factors, such as timing of measurement, add complexity because erythrocyte AChE inhibition persists longer than that in the nervous tissues. Cholinergic transmission might also be impaired because of direct effects of organophosphorus esters and carbamates on receptors.