User:CMoretz/Anticholinesterase poisoning

Anticholinesterase poisoning is a medical condition caused by absorption of cholinesterase-inhibiting pesticides (also known as anticholinesterases or acetylcholine inhibitors) such as organophosphate or N-methyl carbamate insecticides.

Organophosphate poisoning
Symptoms of acute poisoning can develop within minutes to hours, depending on the route of exposure. Inhalation exposure produces symptoms the most rapidly, followed by ingestion and then dermal exposure. The most commonly reported early symptoms are headache, nausea, dizziness, and hypersecretion (sweating, salivation, watery eyes, and runny nose). As the condition worsens, patients display muscle weakness, twitching, tremor, incoordination, vomiting, abdominal cramps, and diarrhea. The poisoned person may experience miosis, reporting blurred or dark vision. Anxiety and restlessness are common. Some psychiatric symptoms have also been reported, including depression, memory loss, and confusion; and toxic psychosis is sometimes present, manifested as confusion or bizarre behavior. Children can present different symptoms than adults: bradycardia, muscular fasciculations, and sweating, and watery eyes are less common, while seizures, lethargy, and coma were more common than in adults.

The primary cause of death in organophosphate poisonings in respiratory failure. Respiratory arrest can occur suddenly. Bronchospasm and broncorrhea sometimes occur, producing chest tightness, wheezing, coughing, and pulmonary edema. In cases of life-threatening severity, the patient will lose consciousness and display incontinence, convulsions, and respiratory depression. There is also typically a cardiovascular component: bradycardia can progress to sinus arrest, though this may be superseded by tachycardia and hypertension from nicotinic stimulation.

Organophosphate-induced delayed neuropathy
In rare cases, a few organophosphates have caused a syndrome called organophosphate-induced delayed neuropathy (OPDIN), which is characterized by weakness or paralysis, and numbness or tingling of extremities. This is caused by the toxins' damage to afferent fibers of peripheral and central nerves associated with inhibition of "neuropathy target esterase." OPDIN primarily affects the legs and last anywhere from a few weeks to several years. This condition is typically found after an acute and often massive exposure.

Intermediate syndrome
An intermediate syndrome has also been described for some cases of organophosphate poisoning. This syndrome generally occurs 24-96 hours after exposure to the chemical, after the acute cholinergic crisis is resolved. It is characterized by acute repiratory and muscular weakness, primarily in the face, neck, and limbs, and is often accompanied by cranial nerve palsies and depressed tenden reflexes.

Exposure
Organophosphates can be absorbed by inhalation, ingestion, and contact with skin. Highly toxic organophosphates are more likely to be better absorbed dermally than moderately toxic ones. The most common exposure scenarios for pesticide-poisoning cases are accidental or suicidal poisonings, occupational exposure, by-stander exposure to off-target drift, and the general public who are exposed through environmental contamination.

Different job functions can lead to different levels of exposure. Most occupational exposures are caused by absorption through exposed skin such as the face, hands, forearms, neck, and chest. This exposure is sometimes enhanced by inhalation in settings including spraying operations in greenhouses and other closed environments, tractor cabs, and the operation of rotary fan mist sprayers.

Pathophysiology
Organophosphate and carbamate insecticides, along with other anticholinesterase compounds, poison insects and mammals, by inactivating the acetylcholinesterase enzyme at nerve endings. Acetylcholinesterase (AChE) removes acetylcholine, which is a neurotransmitter used to activate nerves to smooth and skeletal muscles, autonomic ganglia, and glandular cells, as well as within the central nervous system. AChE inhibitors inactivate the enzyme by phosphorylation. If enough of the toxin is absorbed, the loss of enzyme function leads to the buildup of acetylcholine and overstimulation of the receiving nerve endings.

The high acetylcholine concentration at the nerve junctions of smooth muscles leads to muscle contractions, and at gland cell nerve junctions, secretion. Too much acetylcholine at skeletal muscle junctions can cause muscle twitching, but it can also weaken or paralyze the muscle cell by depolarizing the end plate. In the central nervous system, acetylcholine buildup causes sensory and behavioral disturbances, incoordination, depressed motor function, and respiratory depression. Death from organophosphate poisoning usually results from increased pulmonary secretions combined with respiratory failure.

Organophosphates
Breakdown of organophosphates occurs by hydrolysis in the liver and rates vary widely by compound. Organophosphates that are broken down more slowly may be stored temporarily in body fat. These toxins may cause delayed toxicity when they are released later. Certain organophosphates are particularly toxic because of fat storage. For example, malathion, when stored over a long period of time, can produce by-products that inhbitit the liver enzymes responsible for its degradation, thus enhancing its toxicity. When two or more organophosphates are absorbed, one will often inhibit enzymes needed to break down the other. Liver microsomes convert thions (P=S) on many organothiophosphate compounds to oxons (P=O), which are much more toxic but break down more readily. Both thions and oxons are hydrolyzed, and the resulting alkyl phosphates and leaving groups are transformed by the body and excreted.

Prevention
Remove clothing and wash skin with soap and water Airway management (secretions are the main issue), avoid SCh (degraded by AChE) Atropine (titrated to dried secretions, not HR) and pralidoxime (reactivates AChE)