Myasthenia Gravis and Insecticides

MGnet The Internet Chapter of the MGFA

All links in this article will open a new window. Simply close the window to return to this page.
To Print this article reduce the margins on your printer to their minimum width.

Myasthenia Gravis and Insecticides

by Dale C. Wurtenberger

The most popular insecticides in use today are organophosphates. This class of chemical is designed to kill insects by disrupting their brains and nervous systems. Specifically, they inhibit the function of a key enzyme in the nervous system called cholinesterase.(1) Carbamates are another insecticide that inhibits cholinesterase. Cholinesterase is not only found in insects, but also in humans. Both of these insecticides work similarly to Mestinon®, the brand name for pyridostigmine bromide. They are all cholinesterase inhibitors.

Why should a myasthenic be wary of a chemical that works like the medicine they take to control their disease? Simple, overdose. Mestinon® works for a myasthenic when taken in the correct dosage. Too much Mestinon may cause exacerbation of myasthenia gravis and send a myasthenic into a crisis.

Donald A. Barone, D.O., an MDA Clinic Director, was asked what insecticides a myasthenic should avoid. He said, "Organophosphorous pesticides have potent anticholinesterase properties and may produce a cholinergic crisis in anyone excessively exposed. Myasthenic patients, especially those on anticholinesterase medication, are likely to be more susceptible to the toxic effects."(2)

A myasthenic experiencing severe difficulty breathing or swallowing defines a myasthenic crisis. A cholinergic crisis is a chemically induced overdose of medication or overexposure to an anticholinesterase agent. The symptoms of a cholinergic crisis can include muscle weakness, muscle twitching, sweating, excessive salivation, and constricted pupils. It is frequently difficult to tell the difference between these two crises, but treatment for the first is to increase cholinesterase inhibitors, and treatment for the latter is to decrease cholinesterase inhibitors. A Tensilon test can be used to help differentiate between the two.

There are two other popular insecticides myasthenics need to know about. These are N,N-diethyl-m-toluamide, now called diethyl-3-methylbenzamide (DEET) and permethrin.

A Simplified Explanation of Cholinesterase and
Anticholinesterase Agents

In 1996, Duke Medical Center pharmacologist Mohamed Abou-Donia and Tom Kurt, a toxicologist at The University of Texas Southwestern Medical Center, released their findings in a study involving pyridostigmine bromide, DEET and permethrin.

The study showed that pyridostigmine bromide alone caused no long-term effects, but when combined with either of the insecticides there was a definite problem. DEET products are applied directly to the skin to keep insects from biting. Permethrin products are usually sprayed to repel insects. Normally the immune system deactivates pesticides in animals.

Healthy chickens were used in this study since their nervous systems are most similar to humans. The chickens were first given each chemical separately, and showed no adverse reactions. When exposed to any two of these chemicals the chickens " . . . exhibited varying degrees of weight loss, diarrhea, shortness of breath, decreased activity, stumbling, leg weakness and a reluctance to walk, impaired flying or tremors. The combination of all three chemicals produced the most severe signs, resulting in total paralysis or death in some chickens. "(5) Tissue analysis showed signs of widespread damage to the nervous system. The research indicates that pyridostigmine bromide reduces the body's ability to block the two pesticides, which can then travel to and damage the brain and other parts of the nervous system.

These studies were not conducted for or with myasthenia gravis patients. There is no information on what levels of insecticides can be considered safe or unsafe for a person taking pyrodistigmine bromide.

In January of 2003, the results of another study by Abou-Donia were published in the Journal of Toxicology and Environmental Health. This new study indicates that a combination of pyridostigmine bromide, DEET, permethrin, and moderate stress causes extensive cell degeneration and cell death in the testes of laboratory rats. The higher the stress level, the more damage occurs. Most stages of sperm development were interrupted or eliminated completely. According to Abou-Donia, the rats showed no outward signs of ailments, but under a microscope, the testicular damage could clearly be seen. Whether or not this damage is reversible is yet unknown. The testicular damage corresponds with equally devastating brain damage.(5) Findings from these experiments were published in the August 2002, issue of Neurobiology of Disease.

Pesticides of Concern to Myasthenics

	Myasthenia Gravis and Insecticides by Dale C. Wurtenberger
	Myasthenia gravis patients may be at risk when coming into contact with insecticides. Some of the most commonly used insecticides are intended to disrupt the nervous system of an insect by attacking enzymes which are also found in the neuromuscular junction of a human. Recent studies show that two other insecticides may cause damage to the brain, other parts of the nervous system, and testes when combined with medicines frequently prescribed to myasthenics.
	The most popular insecticides in use today are organophosphates. This class of chemical is designed to kill insects by disrupting their brains and nervous systems. Specifically, they inhibit the function of a key enzyme in the nervous system called cholinesterase.(1) Carbamates are another insecticide that inhibits cholinesterase. Cholinesterase is not only found in insects, but also in humans. Both of these insecticides work similarly to Mestinon®, the brand name for pyridostigmine bromide. They are all cholinesterase inhibitors. Why should a myasthenic be wary of a chemical that works like the medicine they take to control their disease? Simple, overdose. Mestinon® works for a myasthenic when taken in the correct dosage. Too much Mestinon may cause exacerbation of myasthenia gravis and send a myasthenic into a crisis. Donald A. Barone, D.O., an MDA Clinic Director, was asked what insecticides a myasthenic should avoid. He said, "Organophosphorous pesticides have potent anticholinesterase properties and may produce a cholinergic crisis in anyone excessively exposed. Myasthenic patients, especially those on anticholinesterase medication, are likely to be more susceptible to the toxic effects."(2) A myasthenic experiencing severe difficulty breathing or swallowing defines a myasthenic crisis. A cholinergic crisis is a chemically induced overdose of medication or overexposure to an anticholinesterase agent. The symptoms of a cholinergic crisis can include muscle weakness, muscle twitching, sweating, excessive salivation, and constricted pupils. It is frequently difficult to tell the difference between these two crises, but treatment for the first is to increase cholinesterase inhibitors, and treatment for the latter is to decrease cholinesterase inhibitors. A Tensilon test can be used to help differentiate between the two. There are two other popular insecticides myasthenics need to know about. These are N,N-diethyl-m-toluamide, now called diethyl-3-methylbenzamide (DEET) and permethrin.	A Simplified Explanation of Cholinesterase and Anticholinesterase Agents In order for a muscle to move, a nerve impulse is sent from the brain, through the nerve to the nerve ending. A chemical called acetylcholine carries the message across the nerve synapse to the muscle, linking up with the muscle's receptor, because a muscle can only contract when its receptors are flooded with acetylcholine. In myasthenia gravis, some of the muscle receptors are blocked by antibodies that prevent the acetylcholine from doing its job. Cholinesterase is an enzyme that, in normal circumstances, gets rid of the aceytlcholine so that too much of it does not build up at the receptor site. But in myasthenia gravis, a cholinesterase inhibitor, also known as an anticholinesterase agent, can be used to block the cholinesterase from working. This allows the acetylcholine to hang around the receptor longer, flooding the site with acetylcholine and outmaneuvering the antibodies.
	In 1996, Duke Medical Center pharmacologist Mohamed Abou-Donia and Tom Kurt, a toxicologist at The University of Texas Southwestern Medical Center, released their findings in a study involving pyridostigmine bromide, DEET and permethrin. The study showed that pyridostigmine bromide alone caused no long-term effects, but when combined with either of the insecticides there was a definite problem. DEET products are applied directly to the skin to keep insects from biting. Permethrin products are usually sprayed to repel insects. Normally the immune system deactivates pesticides in animals. Healthy chickens were used in this study since their nervous systems are most similar to humans. The chickens were first given each chemical separately, and showed no adverse reactions. When exposed to any two of these chemicals the chickens " . . . exhibited varying degrees of weight loss, diarrhea, shortness of breath, decreased activity, stumbling, leg weakness and a reluctance to walk, impaired flying or tremors. The combination of all three chemicals produced the most severe signs, resulting in total paralysis or death in some chickens. "(5) Tissue analysis showed signs of widespread damage to the nervous system. The research indicates that pyridostigmine bromide reduces the body's ability to block the two pesticides, which can then travel to and damage the brain and other parts of the nervous system.
	These studies were not conducted for or with myasthenia gravis patients. There is no information on what levels of insecticides can be considered safe or unsafe for a person taking pyrodistigmine bromide. In January of 2003, the results of another study by Abou-Donia were published in the Journal of Toxicology and Environmental Health. This new study indicates that a combination of pyridostigmine bromide, DEET, permethrin, and moderate stress causes extensive cell degeneration and cell death in the testes of laboratory rats. The higher the stress level, the more damage occurs. Most stages of sperm development were interrupted or eliminated completely. According to Abou-Donia, the rats showed no outward signs of ailments, but under a microscope, the testicular damage could clearly be seen. Whether or not this damage is reversible is yet unknown. The testicular damage corresponds with equally devastating brain damage.(5) Findings from these experiments were published in the August 2002, issue of Neurobiology of Disease.
	Pesticides of Concern to Myasthenics
	DEET is one of the few pesticides that can be applied to your skin to repel insects. It is found in sprays, liquids, lotions, moist towelettes, wristbands and tablecloths. According to the National Pesticide Information Center, scientists do not completely understand how it works, but think it may effect receptors in mosquito antennae.(6) Abou-Donia recently asked for more government testing of this chemical. He says, "30 years of research on pesticides' brain effects clearly indicate the need for caution among the general public." (7) Health Canada recently banned all products with more then a 30% concentration of DEET. Permethrin was originally developed for the military to be sprayed on clothing and fabric. It is now widely used in agricultural pesticide products on field crops such as cotton, tobacco, hops, fruits and vegetables, and in greenhouses, market gardens and vineyards. It is used in household insect foggers and sprays, flea dips, sprays and most flea collars, repellents for clothing, termite treatments, mosquito treatments, lice shampoos and body lotions for scabies. (8) Permethrin is classified as a Pyrethroid. Pyrethroids are synthetic chemical insecticides frequently used in public health mosquito control programs. High doses of pyrethroids can affect the nervous system, but they are not cholinesterase inhibitors. Pyrethrin is a natural insecticide derived from chrysanthemum flowers. Pyrethrins and pyrethroids are nerve poisons that delay the closing of ion channels. (9)
	Organophosphates, carbamates, and some newer chemicals, such as the chlorinated derivatives of nicotine are cholinesterase inhibitors and may cause a cholinergic crisis. Organophosphates irreversibly bind to cholinesterase unless there is pharmacologic intervention within 24 hours. Carbamates temporarily bind to cholinesterase for approximately six hours. (10 ) The U.S. Environmental Protection Agency web site contains a list of organophosphate pesticides (bottom of page.) http://www.epa.gov/pesticides/op/primer.htm For a list of pesticides that are cholinesterase inhibitors see http://ace.orst.edu/info/extoxnet/tibs/cholines.htm

	References (1) National Resources Defense Council http://www.nrdc.org/health/pesticides/forgano.asp (2) Muscular Dystrophy Association, Ask the Experts http://www.mdausa.org/experts/question.cfm?id=1521&disease=76 (3) Duke University, Duke Med News, April 1996 http://dukemednews.duke.edu/news/article.php?id=797 (4) Radiological Society of North America, November 2000 http://jol.rsna.org/pr/target.cfm?ID=22 (5) Duke University, Duke Med News, January 2003 http://dukemednews.duke.edu/news/article.php?id=6326 (6) NPIC, a cooperative effort of Oregon State University and the U.S. Environmental Protection Agency http://ace.orst.edu/info/npic/factsheets/DEETgen.pdf (7) Duke University, Duke Med News, May 2002 http://dukemednews.duke.edu/news/article.php?id=5500 (8) NPIC, a cooperative effort of Oregon State University and the U.S. Environmental Protection Agency http://npic.orst.edu/factsheets/permethrin.pdf (9) NPIC, a cooperative effort of Oregon State University and the U.S. Environmental Protection Agency http://ace.orst.edu/info/npic/factsheets/pyrethrins.pdf (10) eMedicine, Debra Slapper, M.D., Consulting Staff, Department of Emergency Medicine, St Anthony's Hospital http://www.emedicine.com/emerg/topic346.htm
	This web page is intended to provide the reader with general information to be used solely for educational purposes. The information contained on this web page reflects the views of the author, but not necessarily those of MGnet or the Myasthenia Gravis Foundation of America (MGFA). Any reference to a particular product source or use does not constitute an endorsement. The author is not a medical professional. A special thank you to James F. Howard, Jr., M.D., Chief, Neuromuscular Disorders Section Department of Neurology, The University of North Carolina Chapel Hill, for reviewing this article. © 2003 by MGnet
Home \| Calendar \| Newsletter \|Information\| Join MGnet \| Chat \| Directors \|Contact MGnet \|Donations