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Cholinesterase Inhibitor


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Cholinesterase Background


Cholinesterase , or acetylcholine, produced in the liver, is one of many important enzymes needed for the proper functioning of the nervous systems of humans, other vertebrates, and insects (#EXTOXNET). Nerve impulses are transmitted across synapses through the release of a chemical called acetylcholine. After the stimulating signals are transferred, cholinesterase is released by the body and the acetylcholine is broken down into its acetyl and choline components and removed from the synapse, allowing other signals to pass through (#EXTOXNET). Cholinesterase inhibiting chemicals, most notably organophosphate and carbamate Pesticides, do not allow cholinesterase to end the stimulating signal which causes a build up of stimulating signals in the nervous system. Because they cannot be removed, the stimulating signals continue firing in the body which results in the uncontrollable movements that are the sign of cholinesterase inhibition including rapid muscle twitching, convulsions, and others (#EXTOXNET and #PMEP).

Summary from #EXTOXNET:
"Let us look at a typical synapse in the body's nervous system, in which a muscle is being directed by a nerve to move. An electrical signal, or nerve impulse, is conducted by acetylcholine across the junction between the nerve and the muscle (the synapse) stimulating the muscle to move. Normally, after the appropriate response is accomplished, cholinesterase is released which breaks down the acetylcholine terminating the stimulation of the muscle. The enzyme acetylcholine accomplishes this by chemically breaking the compound into other compounds and removing them from the nerve junction. If acetylcholinesterase is unable to breakdown or remove acetylcholine, the muscle can continue to move uncontrollably."

Pharmacology of Cholinesterase Inhibitors


Cholinesterase inhibitors, most notably Organophosphates and Carbamates, bind to the enzyme cholinesterase and do not allow it to break down stimulating signals which then build up in nerve synapses and result in the health effects below.

Organophosphates inhibit cholinesterase by forming covalent bonds through phosphrylation and the half-life of Organophosphates are days to weeks which is why they are considered more dangerous than Carbamates (#PMEP). Organophosphates affect blood cholinesterase as well as the plasma cholinesterase (the type referred to most on this page as its effects are ore common and more serious) while Carbamates only affect plasma cholinesterase (#PMEP and #EXTOXNET).

Health Effects


The health effects of Organophosphates, Carbamates, and other cholinesterase inhibitors are dose respondent: the amount of the chemical and the duration of exposure are directly proportional to the severity of the symptoms. Some chemicals are more toxic than others. Some symptoms of cholinesterase inhibition are below:

* nausea
* vomiting
* blurring of vision
* chest pain
* involuntary defecation and urination
* salivation
* lacrimation

* diarrhea
* sweating
* excessive bronchial secretions
* weakness
* fasciculations
* flaccid paralysis
* muscle twitching

 

Examples


Other Uses


Medicinal
Cholinesterase inhibitors have been used widely to treat Alzheimer's Disease and many other diseases including some types of dementia, delirium, and some traumatic brain injuries (#Overshott and Burns, 2005).

External Links


References



Pesticide Management Education Program. "CHOLINESTERASE". Accessed 9-20-07.


Extension Toxicology Network. "Toxicology Information Brief - Cholinesterase Inhibition". 9-93. Accessed 9-20-07.


Ross Overshott and Alistair Burns. "Editorial - Cholinesterase inhibitors: in search of cholinergic deficits". Advances in Psychiatric Treatment (2005) 11: 321-324.


Pesticide Action Network Pesticide Database. "Neurotoxicity: Cholinesterase Inhibitors". Last updated November 11, 2002. Accessed 9-20-07.

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