Organic Phosphorous Compound and Carbamate Toxicity

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[1, 2] OPC nerve agents may also be used in the military setting or in terrorist attacks such as the use of sarin in the 1995 Tokyo subway attacks. [3] Carbamates, such as physostigmine and neostigmine, are commonly used to treat diseases such as glaucoma and myasthenia gravis.

Although OPC and carbamates are structurally distinct, they have similar clinical manifestations and generally the same management. Although most patients with OPC and carbamate poisoning have a good prognosis, severe poisoning is potentially lethal. Early diagnosis and initiation of treatment are important. The ED physician has access to a number of therapeutic options that can decrease morbidity and mortality (see Treatment and Medication).

OPCs and carbamates bind to an active site of acetylcholinesterase (AChE) and inhibit the functionality of this enzyme by means of steric inhibition. The main purpose of AChE is to hydrolyze acetylcholine (ACh) to choline and acetic acid. Therefore, the inhibition of AChE causes an excess of ACh in synapses and neuromuscular junctions, resulting in muscarinic and nicotinic symptoms and signs.

Excess ACh in the synapse can lead to 3 sets of symptoms and signs.

First, accumulation of ACh at postganglionic parasympathetic muscarinic acetylcholine receptors leads to parasympathetic activity of smooth muscle in the lungs, GI tract, heart, eyes, bladder, and secretory glands and increased activity in postganglionic sympathetic receptors for sweat glands. This results in the symptoms and signs that can be remembered with the mnemonic SLUDGE/BBB (see Presentation/Physical Examination).

Second, excessive ACh at nicotinic acetylcholine receptors in preganglionic sympathetic synapses and at motor end plates may cause mydriasis, tachycardia, weakness, hypertension, and fasciculations that can be remembered with the mnemonic “days of the week MTWHF”. Third, as OPs cross the blood-brain barrier, they may cause seizures, respiratory depression, and CNS depression for reasons not completely understood.

OPCs and carbamates also bind to erythrocyte cholinesterase (also known as red blood cell [RBC] cholinesterase) on RBCs and plasma cholinesterase (also known as pseudocholinesterase, serum cholinesterase, or butyrylcholinesterase) in the serum. This binding seems to have only minimal clinical effects but is useful in confirmatory diagnostic studies.

The main difference in the mechanisms of action between OPCs and carbamates is that carbamates spontaneously hydrolyze from the AChE site within 24 hours, whereas OPCs undergo aging. Aging occurs when the phosphorylated AChE nonenzymatically loses an alkyl side chain, becoming irreversibly inactivated. Carbamates, however, reversibly bind to the active site and do not undergo aging.

United States

In the United States, more than 18,000 products are licensed for use, and each year more than 2 billion pounds of pesticides are applied to crops, homes, schools, parks, and forests. [4] Occupational exposure is known to result in an annual incidence of 18 cases of pesticide-related illness reported for every 100,000 full-time workers in the United States. [5] In 2016, 2484 cases of OPC exposure, 1404 cases of carbamate exposure, and 47 cases of combined OPC and carbamate exposure were reported to Poison Control Centers in the United States. One OPC-related death and two carbamate-related deaths were reported that year. [6]

International

Because of the increased use and availability of pesticides (especially in developing countries), the incidence of OPC and carbamate poisoning is high. In China alone, pesticide poisoning, mainly with OPCs, cause an estimated 170,000 deaths per year. Virtually all of these are the result of deliberate self-poisoning by ingestion. [7]

Many OPC and carbamate exposures are mild, and symptoms resolve rapidly. The severity of poisoning is largely due to a number of factors, including the type of agent, the amount and route of exposure, and the time to initial treatment. The most common cause of mortality in OPC and carbamate poisoning is respiratory failure; however, death is rare, occurring in 0.04-1% of typical pesticide poisonings. [8]

No racial predilection exists. Men have an increased incidence because of increased work-related exposure and increased suicidal attempts with OP and carbamate compounds.

Children have an increased incidence of unintentional exposure at home. One retrospective study revealed a difference in clinical presentation in children with OPC and carbamate poisoning compared with adults. In pediatric patients, CNS depression and severe hypotonia predominated, whereas muscarinic symptoms were infrequent. [9]

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Daniel K Nishijima, MD, MAS Assistant Professor of Emergency Medicine, Associate Research Director, Department of Emergency Medicine, University of California, Davis, School of Medicine

Daniel K Nishijima, MD, MAS is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Sage W Wiener, MD Assistant Professor, Department of Emergency Medicine, State University of New York Downstate Medical Center; Director of Medical Toxicology, Department of Emergency Medicine, Kings County Hospital Center

Sage W Wiener, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph’s Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Fred Harchelroad, MD, FACMT, FAAEM, FACEP Attending Physician in Emergency Medicine and Medical Toxicology, Excela Health System

Fred Harchelroad, MD, FACMT, FAAEM, FACEP is a member of the following medical societies: American College of Medical Toxicology

Disclosure: Nothing to disclose.

David Vearrier, MD, MPH Associate Professor, Medical Toxicology Fellowship Director, Department of Emergency Medicine, Drexel University College of Medicine

David Vearrier, MD, MPH is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Occupational and Environmental Medicine

Disclosure: Nothing to disclose.

Dana A Stearns, MD Assistant Director of Undergraduate Education, Department of Emergency Medicine, Massachusetts General Hospital; Associate Director, Undergraduate Clerkship in Surgery, Massachusetts General Hospital/Harvard Medical School; Assistant Professor of Surgery, Harvard Medical School

Dana A Stearns, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Organic Phosphorous Compound and Carbamate Toxicity

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