Oximes in acute organophosphorus pesticide poisoning: a systematic review of clinical trials

Abstract

The RCT authors must be congratulated for attempting important studies in a difficult environment. However, their studies did not take into account recently clarified issues regarding outcome, and their methodology is unclear. A generalized statement that pralidoxime should not be used in OP poisoning is not supported by the published results. Oximes may well be irrelevant in the overwhelming self-poisoning typical of the tropics, but a large RCT comparing the current WHO-recommended pralidoxime regimen (>30 mg/kg bolus followed by >8 mg/kg/h infusion) with placebo is needed for a definitive answer. Such a study should be designed to identify any patient subgroups that might benefit from oximes.

Progress in Antidotes (Acetylcholinesterase Reactivators) Against Organophosphorus Pesticides

“…They are usually arising from careless manipulation with OPP or the suicidal use of some OPP (Eddleston 2002). The terrorist misuse of the OPP should also not be underestimated from the point of view of food or water supplies contamination (Satoh 2000).…”

“…However, the pralidoxime was introduced to clinical practice without relevant clinical studies (Eddleston 2008). Thus, some randomised and double blind placebo controlled trials were made in the last two decades (Johnson 1996, Cherian 1997, Eddleston 2002. However, the opinion on pralidoxime effectiveness or ineffectiveness during OPP poisoning treatment had varied among such trials from the point of e.g.…”

Differential binding of bispyridinium oxime drugs with acetylcholinesterase

“…Intentional (in a suicidal attempt [28] ) or unintentional (through trace dietary contaminants [29] or through chemical warfare [30] ) OP intoxication is a major threat to human kind. While intoxication by OPs accounts for up to 80% of pesticide-related hospitalization [31] , the possibilities of terrorist attacks (like the Iraqi weaponized sarin attack against the Kurdish [32] or the Tokyo subway sarin attack [33] ) with nerve agents looms large, and thus the discovery of effective OP antidotes is necessary and urgent [34][35][36][37][38][39][40][41][42][43][44][45][46] . Thus, fundamental studies [16,17] elucidating the passage of molecules through the AChE gorge into the active triad of the enzyme is of paramount importance for the discovery of new drugs.…”

“…However, prior to aging, the inhibited enzyme can be reactivated by strong nucleophiles, such as oximes. The medical management of an OP victim includes drugs such as atropine (a muscarinic receptor antagonist that artificially maintains the respiration capacity), diazepam (or similar anticonvulsant drug, commonly administered to treat seizure) and oxime reactivators [34][35][36][37][38][39][40][41][42][43][44][45][46] (which liberate the inhibited enzyme). Since aging of an inhibited enzyme occurs within minutes to hours and results in the permanent disability of the enzymatic activity of AChE, the victim should be administered these drugs as soon as possible [49] .…”

Are Oximes Still Indicated for Acute Organophosphorus Insecticide Self-Poisoning?

“…However, subsequent experience suggested that pralidoxime was less effective for certain OP insecticides, such as malathion, and following oral ingestion for self-harm. [9,10] This impression fitted with the poor clinical experience of pralidoxime in Asian hospitals treating patients with OP selfpoisoning [11], in which a lack of pralidoxime was not apparently associated with worse outcome [12]. The clinical toxicology community's response to this lack of effect was that too low a dose was being used [13,14].…”