HYPOTHESIS FOR SYNERGISTIC TOXICITY OF ORGANOPHOSPHORUS POISONING-INDUCED CHOLINERGIC CRISIS AND ANAPHYLACTOID REACTIONS

The neurotoxicity of organophosphorus (OF) compounds involves the inhi bition of acetylcholinesterase (AChE), causing accumulation of acetylc holine (ACh) at synapses. However, cholinergic crisis may not be the s ole mechanism of OP toxicity, Adverse drug reactions caused by synergi stic toxicity between drugs with distinct pharmacological mechanisms a re a common problem, Likewise, the multiple pharmacological activities of a single molecule might also contribute to either toxicity or effi cacy. For example, certain OP compounds (e.g. soman) exhibit anti-AChE activity and also act as secretagogues by inducing mast cell degranul ation with associated autacoid release and anaphylactoid reactions. An aphylactoid shock can produce a lethal syndrome with symptoms of respi ratory failure and circulatory collapse similar to the physiological s equelae observed for OP poisoning. Moreover, the major classes of drug s used as antidotes for OP intoxication can affect anaphylaxis. Acetyl choline can act as an agonist of autacoid release, and autacoids such as histamine can augment soman-induced bronchial spasm. In concert wit h the demonstrably critical role of cholinergic crisis in OP toxicity, the precepts of neuroimmunology indicate that secondary adverse react ions encompassing anaphylactoid reactions may complicate OP toxicity.