146 - Insecticides, Herbicides, and Rodenticides

The clinical severity and toxicodynamics vary according to the agent, the route of absorption, and whether the exposure was intentional. Regardless of these factors, the toxicologic mechanism of acetylcholinesterase (AChE) inhibition remains consistent. The end result is an excess of the neurotransmitter acetylcholine (ACh), which results in overstimulation of muscarinic and nicotinic receptors and production of a cholinergic toxidrome. Under normal circumstances, ACh is hydrolyzed by AChE to yield acetic acid and choline. In the presence of OP insecticides, AChE is phosphorylated, whereas in the presence of carbamate insecticides, the enzyme is carbamylated. As a result, the rate of regeneration of active AChE is slowed, and its function is inhibited. Within 24 to 72 hours of OP poisoning, an alkyl group may dissociate from the AChE-OP complex and thereby result in “aging” of the AChE. Once aging occurs, reactivation of AChE is no longer possible, and only synthesis of new enzyme can restore activity. In the case of carbamate poisoning, breakdown of the carbamate-AChE complex occurs much more rapidly and aging does not occur (Box 146.1). ACh accumulates in the autonomic nervous system at postganglionic muscarinic (parasympathetic and sympathetic) receptors and preganglionic nicotinic (sympathetic) receptors. It also accumulates at the neuromuscular junction and in the central nervous system (CNS). Overstimulation of these receptors is responsible for the cholinergic toxidrome seen with OP and carbamate insecticide poisoning (Table 146.1). • Organophosphorus and carbamate poisonings cause excessive stimulation of muscarinic and nicotinic receptors by acetylcholine, which can potentially lead to life-threatening bronchorrhea and bronchospasm. • Aggressive airway management and liberal use of atropine are important in the management of both organophosphorus and carbamate poisoning. • Only a nondepolarizing neuromuscular blocker, such as vecuronium or rocuronium, should be used for intubation. Succinylcholine is metabolized by plasma cholinesterase, and prolonged paralysis may result if it is used in the setting of organophosphate poisoning. • Timely administration of pralidoxime is key to the treatment of organophosphorus poisoning, but pralidoxime is not indicated for carbamate poisoning. • Unintentional pediatric ingestion of 4-hydroxycoumarins (superwarfarins) accounts for the vast majority of rodenticide exposures and rarely results in toxicity. • Ingestion of an anticoagulant rodenticide should be considered when a child younger than 6 years has an elevated prothrombin time or bleeding without another explanation. • The prothrombin time should be measured at 24 and 48 hours after large ingestions of 4-hydroxycoumarins. • Because no specific antidote or pharmacologic intervention has proved beneficial in treating paraquat or diquat poisoning, early decontamination is the most important step. KEY POINTS