Part 4: The Cholinergic Toxidrome

Section 9: Importance of the Exposure History

Learning Objectives

Upon completion of this section, you should be able to

  • Identify potential sources of exposure to cholinesterase inhibitors.
  • Identify the important elements to include in an exposure history when evaluating patients who might be suffering from cholinesterase inhibitor toxicity.

There does not appear to be much data on how often cholinesterase-based pharmaceuticals, plant and animal toxins, and industrial substances cause toxicity.

However, probably the most frequent source of cholinesterase inhibitor exposure is from pesticides. While estimates vary widely, one source suggests that pesticides cause 3 million poisonings and 200,000 deaths world-wide each year. The American Association of Poison Control Centers reported 86,914 pesticide exposures in 1996. (Clark 2002)
The exposure history can be a valuable aid in identifying patients who might be suffering from cholinesterase toxicity.

See the Case Study on Taking an Exposure History available at

Note: While cholinesterase inhibitor poisoning may go unrecognized because of the failure to take an exposure history, the exposure history can also be deceiving. For example, In one study, 88% of parents of patients with organophosphate poisoning denied any exposure history. (Reigart and Roberts 1999)

Where Cholinesterase Inhibitors are Found

Some sources of cholinesterase inhibitors are listed in the following table.

Where Cholinesterase Inhibitors are Found
Source Examples
Insecticides Carbamates
Organophosphorus compounds
Nerve agents used in chemical warfare and chemical terrorism Sarin
Pharmaceuticals (Lotti 1992; Hoffman and Taylor 2001; Taylor 2001) Donepezil used for Parkinsonism
Neostigmine used for paralytic ileus or urinary bladder atony
Physostigmine used for glaucoma or as an antidote for anticholinergic poisoning
Pyridostigmine used for myesthenia gravis or prophylaxis against nerve agent exposure
Tacrine used for Parkinsonism
Poisonous plants and animals (Karalliedde 1999; Kassa 2002) Bittersweet
Calabar beans
Fish hunting cone snails
Potato sprouts
Venomous snakes
Industrial materials (Karalliedde 1999) Fire retardants
Lubricant additives
Traditional remedies (Karalliedde 2002) Huperazine A (Chinese remedy)
Solanine and chaconine in potatoes used in Africa to treat HIV
Home Exposures

Exposures occur in the home after it has been sprayed or fogged with pesticides. (Clark 2002)

Outbreaks of poisoning have occurred from contaminated crops or food. (Erdman 2004)

Suicidal ingestions are particularly widespread in countries, such as India, Sri Lanka, Turkey, Taiwan, and parts of Africa. (Ecobichon 1996).

Children may be exposed when pesticides are stored in unlabeled containers or beverage bottles, or when they play in recently sprayed fields. Insecticides (including those that are cholinesterase inhibitors) were involved in 4.2% of poisonings in 2004 in children younger than 6 years of age. (Watson, Litovitz et al. 2004)

Occupational Exposures

Occupations associated with exposure to cholinesterase inhibitors include the following:

  • Agricultural workers. (Ecobichon 1996; Jaga and Dharmani 2003)
  • Crop duster pilots and ground crews. (Ecobichon 1996)
  • Florists. (Jaga and Dharmani 2003)
  • Gardeners and nursery workers. (Ecobichon 1996)
  • Greenhouse workers. (Jaga and Dharmani 2003)
  • Mosquito abatement workers. (Marrs and Dewhurst 2000)
  • Pest control workers. (Ecobichon 1996)
  • Insecticide applicators, exterminators. (Jaga and Dharmani 2003)
  • Insecticide manufacturers. (Jaga and Dharmani 2003)
  • Pet groomers.
  • Veterinary workers. (Jaga and Dharmani 2003)
Consumer Exposures

Consumers can be exposed to cholinesterase inhibitors by means of the following:

  • Spillage onto food products during storage or transport. (Marrs and Dewhurst 2000)
  • Ingestion of seed grain or seed potatoes treated with pesticides (not intended for consumption). (Marrs and Dewhurst 2000)
  • Improper application of pesticides.
Exposure History Questions

Below are some  focused exposure history questions that should be asked of patients (and household members) when signs and symptoms are consistent with or suggestive of cholinesterase inhibitor toxicity.

  • What kind of work do you do? (Inquire about work done by other residents of the household as well.)
  • Describe typical work activities (tasks, locations, materials, and substances used).
  • Describe any recent changes in work activities or changes that coincide with symptom development. Include any work done outside of regular employment (e.g., volunteer work).
  • What are your hobbies and outside activities (e.g., gardening, flower arranging, animal-related activities)?
  • Do you consume wild mushrooms?
  • Do you handle venomous snakes?
  • What chemicals are used at your work locations? Material Safety Data Sheets (MSDS), obtainable from employers, may contain valuable information about chemicals used at that location. While studies have shown that a significant number of MSDS documents contain incomplete or incorrect information, this mostly relates to chronic toxicity data.) (Greenberg, Cone et al. 1996)
  • Are pesticides used or manufactured at your workplace?
  • Do you transport chemicals? pesticides? (Specify product names.)
  • Do you come into contact with them? When? How often? What type of contact? (Skin, inhalation?)
  • Do symptoms occur at any particular time of day? day of week? after any particular type of activity?
  • Does anyone else at home or work have similar symptoms?
  • What medicines have you been taking? Have you used any traditional or herbal remedies?
  • Do you use pesticides at work?
  • Do you use pesticides at home (e.g., garden sprays or granules, flea or tick sprays or collars, animal shampoos)?
  • When you use pesticides, do you wear protective gloves? respirator? clothing? Do you wash/shower/change clothes afterwards? Have you received instructions on the use of Personal Protective Equipment (PPE)? Does unwashed protective wear or work clothing come into contact with other household laundry?
  • Do you shower/wash hands after using? Do you change clothes? Who handles the contaminated clothes? Do you smoke or eat prior to washing and changing clothes after handling pesticides?
Key Points
  • Cholinesterase inhibitors are found in pharmaceuticals, pesticides, chemical warfare agents, industrial materials, and traditional medical remedies.
  • Taking an exposure history may be helpful in diagnosing cholinesterase inhibitor toxicity