Pulmonary Toxicity of Cholinesterase Inhibitors
Abstract
The lungs are a major organ system of entry into the body and a target for the toxic effects of organophosphorus (OP) corn- pounds, potent inhibitors of the enzyme acetyicholinesterase (AChE). In general, AChE inhibitors (AChEIs) were developed for a variety of indications, including military, medical, and insecticide applications. Nerve agents, OP chemicals with remarkable toxic activity, were first developed by Germany prior to World War II. Whereas nerve agents were produced primarily for military deployment, other cholinesterase inhibitors were used for treating conditions such as myasthenia gravis and as pretreaunents for nerve agent exposure. As powerful inhibitors of AChE, these compounds exhibit profound toxicity on multiple organ systems. This chapter discusses respiratory and pulmonary toxicity through direct inhalation of AChEIs and indirect effects on all aspects of respiration through systemic toxicity. OP nerve agents can be disseminated as liquids or aerosols and are toxic by oral, dermal, or inhalational exposure. The lungs are one of the first organs affected following contact with aerosols and vapors. Lung toxicity by AChEIs is due to the following: (1) parasympathetic muscarinic effects leading to increased glandular secretion throughout the respiratory tract and alveoli, (2) bronchoconstriction from contraction of airway smooth muscle, (3) nicotinic effects on respiratory muscles in the thorax and accessory muscles of the neck causing labored breathing and eventually flaccid paralysis, and (4) central effects resulting in a decrease in respiratory drive.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2006
- Accession Number
- ADA468769
Entities
People
- Corey Hilmas
- Michael Adler
- Ramesh C. Gupta
- Steven I. Baskin
Organizations
- United States Army Medical Research Institute of Chemical Defense