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Toxicity, Organic Phosphorous Compounds and Carbamates
Updated: Aug 23, 2007
Introduction
Background
The ED physician may encounter organophosphorous compound (OPC) and carbamate poisoning in a variety of clinical scenarios. Pesticide poisoning is the most common cause of OPC and carbamate poisoning because the vast majority of pesticides still contain OPCs and carbamates. OPC nerve agents may be used in the military setting or in terrorist attacks. An example was sarin used in the Tokyo subway attacks of 1995. 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.
Pathophysiology
OPCs and carbamates bind to 1 of the active sites 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 muscarinic synapses 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 Physical below). Second, excessive ACh at nicotinic motor end plates causes persistent depolarization of skeletal muscle (analogous to that of succinylcholine), resulting in fasciculations, progressive weakness, and hypotonicity. 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 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.
Frequency
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.1 Occupational exposure is known to result in an annual incidence of 18 cases of pesticide-related illness reported for every 100,000 workers in the United States.2 In 2003, approximately 7500 cases of OPC and 3700 cases of carbamate exposure were reported to Poison Control Centers in the United States. Sixteen OPC-related deaths and 2 carbamate-related deaths were reported that year.3
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.4
Mortality/Morbidity
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.5
Race
No racial predilection exists.
Sex
Men have an increased incidence because of increased work-related exposure and increased suicidal attempts with OP and carbamate compounds.
Age
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. Pediatric patients had predominately CNS depression and severe hypotonia, whereas muscarinic symptoms were infrequent.6
Clinical
History
Patients usually have a history of OPCs or carbamates exposure, either suicidal or unintentional. Pesticides can rapidly be absorbed through the skin, lungs, GI tract, and mucous membranes. The rate of absorption depends on the route of absorption and the type of OP or carbamate. Symptoms usually occur within a few hours after GI ingestion and appear almost immediately after inhalational exposure.
Physical
In the Tokyo sarin attack, miosis was the most common (>90%) indicator of OP poisoning.7 Bradycardia is not a reliable finding, and patients may be tachycardic, for 2 reasons: First, hypoxia due to bronchorrhea and bronchospasm can lead to sympathetic outflow, which overrides parasympathetic vagal stimulation of the heart and which causes tachycardia. Second, nicotinic ACh receptors are present in both sympathetic and parasympathetic ganglia. These ganglionic effects in the sympathetic system may contribute to tachycardia.
Patients often present with evidence of a cholinergic toxic syndrome, or toxidrome. It is useful to remember the toxidrome in terms of the 3 clinical effects on nerve endings: nicotinic effects at neuromuscular junctions and autonomic ganglia, CNS effects, and muscarinic effects. Nicotinic signs and symptoms include weakness, fasciculations, and paralysis, whereas CNS effects may lead to seizures and CNS depression. Two common mnemonics to remember the muscarinic signs and symptoms of the cholinergic toxidrome are SLUDGE/BBB and DUMBELS, as follows:
- SLUDGE/BBB mnemonic
- S = Salivation
- L = Lacrimation
- U = Urination
- D = Defecation
- G = GI symptoms
- E = Emesis
- B = Bronchorrhea
- B = Bronchospasm
- B = Bradycardia
- DUMBELS mnemonic
- D = Diarrhea and diaphoresis
- U = Urination
- M = Miosis
- B = Bronchorrhea, bronchospasm, and bradycardia
- E = Emesis
- L = Lacrimation
- S = Salivation
Causes
Agricultural exposure is the most common cause of OPC and carbamate poisoning. The World Health Organization (WHO) classifies these poisonings as class I (extremely toxic) to class III (slightly hazardous). The WHO advocates banning or strong restrictions on the use of class I pesticides and a reduction in the use of pesticides to a minimal number of compounds that are less hazardous than others.8
OPCs may also be encountered in the military setting or as the result of a terrorist attack with nerve agents such as sarin, VX, or soman.
In addition to their use as insecticides, carbamates are used to treat certain medical diseases, such as glaucoma and myasthenia gravis (neostigmine, physostigmine). Some case reports describe clinical illness from foodborne outbreaks due to contamination with OPC-containing pesticides.9
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 Overview: Toxicity, Organic Phosphorous Compounds and Carbamates |
| Differential Diagnoses & Workup: Toxicity, Organic Phosphorous Compounds and Carbamates |
| Treatment & Medication: Toxicity, Organic Phosphorous Compounds and Carbamates |
| Follow-up: Toxicity, Organic Phosphorous Compounds and Carbamates |
| References |
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Further Reading
Keywords
pesticide exposure, organic phosphorous compound poisoning, OPC poisoning, carbamate poisoning, pesticide poisoning, pesticides, physostigmine, neostigmine, nerve agent, self-poisoning, toxic ingestion, toxidrome, suicidal ingestion, accidental ingestion, Tokyo subway sarin attack, VX, soman, agricultural exposure, organophosphate toxicity, carbamate toxicity, organophosphate exposure, carbamate exposure, pesticide toxicity
