ReviewNeurotoxic effects in patients poisoned with organophosphorus pesticides
Introduction
Organophosphorus compounds (OP) have been used as pesticides and developed as warfare nerve agents such as soman, sarin, tabun, VX and others. Pesticide poisoning can result from occupational, accidental and intentional exposure (Clark, 2002). The epidemiological pattern of poisoning shows significant variation in number of deaths and form of poisoning between developing and industrial countries (Baker et al., 1978, Jeyaratnam, 1990, van der Hoek et al., 1998, Eddleston, 2000, Eddleston and Phillips, 2004). According to the World Health Organization, about 1 million accidental and 2 million suicidal poisonings with organophosphorus insecticides are reported per year, with more than 300,000 fatalities (Jeyaratnam, 1990). Medical management is difficult, with case fatality generally more than 15% (Eddleston et al., 2008).
Organophosphorus esters cause several neurotoxic disorders in humans: the cholinergic syndrome, the intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP) and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes, arising from severe exposures, may be caused either by OP pesticides or warfare nerve agents. Most of the cases of poisoning can be prevented by better administrative control, restricted access to OP pesticides, effective measures of personal protection and education of OP pesticide applicators and medical personnel.
The objective of this review is to discuss clinical presentation, pathogenesis and molecular mechanisms of neurotoxic effects after acute and chronic exposure to OP pesticides including the possibilities for prevention/treatment.
Section snippets
The cholinergic syndrome
Signs and symptoms of cholinergic syndrome occurring in acute poisoning with OP pesticides are predictable from their biochemical mechanism of action and are directly related to the levels of acetylcholinesterase (AChE) activity. In cases of human poisoning, general acute symptoms of peripheral nicotinic and muscarinic intoxication are clearly apparent (World Health Organization, 1986; Table 1). These symptoms include miosis (unreactive to light); sweating, rhinorrhea, lacrimation, and
Intermediate syndrome
The term Intermediate Syndrome (IMS) was first described by Senanayake and Karalliedde (1987) because it appeared in the interval between the end of the cholinergic crisis and the onset of OPIDP. Following exposure to various OP pesticides, clinical manifestations of IMS typically occur within 24–96 h, and affect patients without fasciculation or other cholinergic signs. The reported incidence of IMS ranges from 7.7% to as high as 84% (Shailesh et al., 1994). Although IMS is well recognized as a
Organophosphate-induced delayed polyneuropathy
Organophosphate-induced delayed polyneuropathy (OPIDP) is unique toxicological phenomenon in that it is caused by a single exposure to certain OP with effects usually appearing after 10–20 days or later. OPIDP is toxicologically different from OP poisoning in that it is based on different mechanisms which do not involve AChE and appear a few weeks after OP poisoning has been medically solved with standard therapeutic measures and patient dismissed from hospital. OPIDP is also a different
Chronic organophosphate-induced neuropsychiatric disorder
Chronic exposure to OPs has been associated with impaired neurobehavioral performance in some, but not all, epidemiological studies (Ray and Richards, 2001). Chronic organophosphate-induced neuropsychiatric disorders (COPIND) occur without cholinergic symptoms and apparently are not dependent on AChE inhibition (Ray and Richards, 2001, Singh and Sharma, 2000). COPIND usually appears with a delay and persists for a long period possibly suggesting the permanent damage of the CNS (Savage et al.,
Conflict of interest
None declared.
Acknowledgement
The research of M.J. was supported by grants from the Serbian Ministry of Science (Projects 145030 and 145035).
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