Organophosphates
Organophosphates (OPs) are present in nearly 40% of all pesticides used in this country. They are highly lipid soluble and are easily absorbed through the skin and respiratory tract. Toxic exposures occur commonly in farmers, gardeners, crop dusters, and pesticide handlers. OPs are also readily absorbed through the GI tract. Accidental ingestion by children and intentional ingestion in suicide attempts represent an unfortunately high number of exposures annually. Their ability to produce paralysis of smooth and striated muscles has made them useful as agents of chemical warfare.8
OPs produce their toxic effects by binding to acetylcholinesterase (AChE). Inhibition of this important enzyme results in excess acetylcholine at neuromuscular junctions and at certain locations in the brain. The peripheral nervous system effects, including excessive salivation, lacrimation, sweating, and diarrhea, are widely recognized as signs of OP toxicity. The acute CNS effects may be mild and are often overshadowed by the peripheral effects at lower levels of exposure. With increased exposure levels, however, encephalopathy, dizziness, and hallucinations become more apparent. Severe encephalopathy, seizures, coma, and death may occur in cases of high levels of exposure. Different OP compounds may result in varied CNS effects, reflecting the distribution of different types of AChE throughout the brain.8,67
The delayed effects of OP toxicity on the peripheral nervous system can be debilitating and have been the focus of much attention in the literature. Prolonged CNS dysfunction is also a matter for concern. Studies indicate that cholinesterase inhibitors can cause changes in the mediation of cholinergic neurotransmission in the brain. Victims of high levels of OP exposure later score worse on mood inventories and on tests of sustained visual attention than their nonexposed counterparts.68,69 Case reports suggest that executive function, memory, and certain learning domains may be impaired for prolonged periods in some individuals, but slow recovery of most functions is the trend.70–73 Further studies are needed before conclusions can be drawn with regard to long-term brain dysfunction in the setting of chronic, low-level OP exposure.
Given the ease of absorption through the skin and respiratory tract, use of protective masks, gloves, and proper clothing is paramount to preventing toxic OP exposure. OPs should be kept well out of the reach of children and should be stored in well-marked containers. The ACGIH suggests monitoring of OP exposure in high-risk settings. Plasma cholinesterase activity levels are more sensitive to low-level exposure, but erythrocyte AChE activity is a better indicator of neuronal AChE inhibition.8
In the event of skin exposure, the skin should be immediately and thoroughly cleansed with soap and water. Any saturated clothing should be removed. In cases of OP ingestion, immediate gastric lavage is warranted to remove as much of the toxin as possible before absorption is complete. Cathartics should also be considered. When given early, oximes such as pralidoxime or obidoxime chloride are useful in minimizing subsequent peripheral neuropathy. These agents do not readily cross the BBB and are therefore less effective in reversing CNS toxicity. Atropine may be used to counteract the muscarinic effects of OPs, but it will not reverse the nicotinic effects and muscle weakness will therefore not improve. Atropine should be administered in small doses (0.5 to 1.0 mg) at 15-minute intervals until signs of OP reversal are apparent. Cessation of sweating and salivation, facial flushing, and papillary dilation signal effective reversal of toxicity. Due to the tendency for OPs to be stored in fatty tissues, continued observation and less frequent dosing of IV atropine (1 to 2 mg every hour) may be needed.8,74 It should be noted that when seizures occur as a result of OP exposure, the mechanism is increased neuronal stimulation by excessive acetylcholine. These seizures do not respond robustly to dilantin or other antiepileptics and should be treated with atropine.75