Organophosphorus Pesticides

Abstract

AbstractOrganophosphates (OP) inhibit serine hydrolases by phosphorylating serine residue. Exposure to OPs always involves acetylcholine esterase (AChE) inhibition, which is responsible for the degradation of acetylcholine (ACh), controlling the levels of ACh at the nerve endings. Inactivation/inhibition of AChE causes excessive accumulation of ACh at the neuromuscular junctions and synapses activating both sympathetic and parasympathetic processes causing both muscarinic and nicotinic toxicity. The muscarinic symptoms include salivation, diaphoresis, abdominal cramps, diarrhea, vomiting, miosis, bronchorrhea, bradycardia, coma, and seizure. Nicotinic symptoms are fasciculations, flaccid paralysis, and tachycardia. The most common cause of death is respiratory failure with refractory hypotension. Recovery from OP toxicity is linked to the restoration of OP‐inhibited AChE, which can be revived by oximes or regeneration of the enzyme, certain OPs bind irreversibly with AChE render it permanently inactive. The secondary OP targets in humans are butyrylcholinesterase (BChE), a sink for OP, and neuropathy target esterase, inhibition of which causes delayed neuropathy. The OPs are not only used for the management of pests in agriculture but also used in the treatment of human diseases, such as glaucoma with echothiophate to increase drainage of intraocular fluid reducing ocular pressure, schistosomiasis, and Alzheimer's with metrifonate. Metrifonate inhibits AChE in schistosomes, which is abundant in the muscles of the parasite. Metrifonate enhances central nervous system (CNS) cholinergic neurotransmission improving cognitive function in Alzheimer's patients. This chapter describes the AChE inhibition and toxicity of each OP and regeneration of AChE by oximes along with regulations based on the available data for individual OPs.