Chapter 31 - Local and Systemic Ophthalmic Pharmacology and Toxicology of Organophosphate and Carbamate Anticholinesterases

Abstract

The chapter discusses the nature of toxic and pharmacological effects produced by anticholinesterases (anti-ChEs) as a result of their topical and/or systemic exposure to the eye, their investigation by laboratory in vitro and in vivo tests and by human clinical studies, and their practical and clinical implications. Human subjects may be exposed to carbamate (CM) or organophosphate (OP) anti-ChEs topically and/or systemically as a consequence of the wide range of their uses, which may result in exposures from deliberate, incidental, or accidental situations. The eye may be a local target organ for toxic and/or pharmacological effects of anti-ChEs that are applied by direct (topical) contact to the eye or that reach the eye from blood circulation. The various circumstances and conditions that determine the site and nature of effects are presented. ChEs, both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), are widely distributed in the eye. Many of the ocular pharmacological effects and some of the ocular toxic effects of anti-ChEs are attributable to their inhibitory effect on ChEs, and the resultant cholinergic response, but some toxic effects may be related to other properties of the molecule that are not a function of its anti-ChE potency. ChE inhibitors may produce varying types of corneal and ocular injury because of their chemical structure that is unrelated to anti-ChE activity, and for this reason, it is necessary to undertake eye irritation studies on the OP or CM pesticides and medical products, and their formulations.