Organophosphorus pesticide poisoning remains a major public health concern due to widespread agricultural use and easy availability of these compounds. Atropine is the cornerstone of treatment for life-threatening muscarinic manifestations. However, repeated or prolonged administration can cause central anticholinergic toxicity, which may closely resemble the neurological effects of organophosphorus poisoning and delay the correct diagnosis. We report a 26-year-old woman who developed severe cholinergic toxicity after intentionally ingesting monocrotophos and was treated with mechanical ventilation, pralidoxime, and atropine. After 48 hours of atropine therapy, she developed acute agitation, hallucinations, disorientation, and peripheral anticholinergic findings despite resolution of her initial cholinergic symptoms. Other metabolic, infectious, and toxicological causes were not identified. Her symptoms resolved after atropine was discontinued, without cholinergic rebound. This case emphasizes the importance of distinguishing atropine-induced delirium from ongoing organophosphorus central nervous system (CNS) toxicity. Regular clinical reassessment and symptom-guided atropine titration may prevent unnecessary investigations, inappropriate treatment, and avoidable anticholinergic complications.

Current oxime antidotes exhibit poor blood-brain barrier (BBB) penetration due to their permanent positive charge, limiting the reactivation of organophosphorus (OP)-inhibited cholinesterases in the central nervous system. To address this limitation, the present study investigates nine lipophilic cholesterol- and quinoline-based oximes as potential reactivators of human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) inhibited by OP compounds. Several oximes exhibited strong reversible inhibition with pronounced potency toward hBChE (Ki as low as 4.6 nM). However, despite the favourable binding affinities, reactivation assays using sarin- and cyclosarin-inhibited enzymes revealed negligible recovery of enzymatic activity compared with the standard antidote pralidoxime (2-PAM). Molecular modelling of near-attack conformations showed that the oxime group of the most potent inhibitor adopted an unproductive orientation relative to the catalytic serine. These results highlighted that binding affinity alone is insufficient for effective reactivation; precise positioning of the oxime moiety to enable nucleophilic access to the phosphorus centre is critical. Therefore, a strategic framework for designing next-generation oxime reactivators based on such structures is needed to improve functional efficacy. Moreover, the moderate cytotoxicity of nitronesteroids in hepatocarcinoma (HepG2) and neuroblastoma (SH-SY5Y) cell lines warrants further studies to assess their implications for the compounds' therapeutic potential and safety profile.

Organophosphate poisoning is a major cause of acute cholinergic toxicity and can progress rapidly to respiratory failure and death. In the emergency setting, diagnosis is often clinical, and treatment should not be delayed while awaiting confirmation of the specific compound. We report a case of a 30-year-old male patient who presented after intentional ingestion of a large reported volume of diazinon-containing pesticide. Within approximately 30 minutes of ingestion, he developed acute cholinergic manifestations, including bradypnea, bradycardia, hypotension, hypersalivation, vomiting, diarrhea, and depressed level of consciousness, complicated by a generalized tonic-clonic seizure. The seizure was treated with diazepam, and atropine was initiated before transfer to the emergency department. On arrival, the patient was in severe respiratory distress with profuse secretions and required urgent endotracheal intubation and mechanical ventilation. Empiric treatment for suspected organophosphate poisoning was continued with atropine and pralidoxime, alongside supportive care. Collateral history later identified the ingested product as Diacidol 600 Emulsifiable Concentrate, containing diazinon 600 g/L, equivalent to 60% weight/volume. Plasma butyrylcholinesterase, red blood cell acetylcholinesterase, and toxicological confirmation testing were not available at our institution at the time of evaluation, which represents a limitation of this report. The patient was admitted to the intensive care unit and managed with atropine and pralidoxime infusions, ventilatory support, and close monitoring for delayed neuromuscular complications. His cholinergic features resolved, and he was successfully extubated within 24 hours. Antidotal therapy was discontinued after sustained clinical improvement, and he remained stable during subsequent ward observation. This case emphasizes that severe organophosphate poisoning remains a clinical diagnosis during initial resuscitation. Early airway protection, titrated atropinization, pralidoxime therapy, benzodiazepines for seizures, and observation for delayed complications are central to favorable outcomes.

Organophosphates (OP) have a variety of applications, including widespread use as pesticides. Although OP poisoning in the U.S. has been declining, toxicity from intentional ingestions of commercially available preparations is still a concern. We describe a case of a 17-year-old female who intentionally ingested an acephate-based fire ant insecticide and developed severe cholinergic toxicity, despite acephate's classification as a safer OP. The patient was successfully treated with atropine and pralidoxime, but had recurrence of symptoms after long asymptomatic periods requiring repeat dosing, which is atypical. We encourage clinicians to have a low threshold for prolonged observation in these patients, even in the absence of symptoms.

Pesticides, as pervasive environmental pollutants, have been associated with cardiotoxic effects. However, evidence regarding cardioprotective strategies remains fragmented, particularly concerning the integration of conventional therapies and nonconventional approaches involving natural products. This systematic review (PROSPERO:CRD420251143191) aimed to synthesize experimental evidence on cardioprotection against pesticides, with emphasis on natural product-based interventions. The review was conducted according to PRISMA, with searches performed in Medline/PubMed, EMBASE, and BVS. Eligible studies included in vitro and in vivo models of pesticide exposure that reported cardiovascular outcomes and therapeutic interventions. A total of 85 studies were included, predominantly involving in vivo models. While only a few studies evaluated conventional antidotes, such as atropine and pralidoxime, most investigated natural and bioactive compounds, including antioxidant vitamins, polyphenols, flavonoids, carotenoids, and microbiota-modulating agents. Frequently studied compounds included vitamin E, vitamin C, lycopene, coenzyme Q10, resveratrol, and curcumin. Overall, these interventions demonstrated protective effects through attenuation of lipid peroxidation, restoration of endogenous antioxidant defenses, and modulation of inflammatory and apoptotic pathways. Studies also reported improvements in hemodynamic and electrocardiographic parameters. Collectively, these findings provide promising preclinical evidence that novel interventions may mitigate pesticide-induced cardiotoxicity, although they should be interpreted with caution due to the predominantly preclinical nature of the studies.

Acute poisoning is a severe global public health issue that involves injury or death caused by exposure to an exogenous substance through any route. This study evaluated the most common poisons, reasons for poisoning, clinical management of poisoning cases, and their associated outcomes. One-year prospective cohort study executed at an academic medical center in Sindh, Pakistan. The predictors of outcomes are examined using a binary logistic regression model. Among 1404 enrolled patients, the majority were male (57.1%), aged 16-30 years (63.2%) and married (77.6%). Organophosphate compounds (42.8%) were the primary reasons for poisoning. Clinical manifestations as abnormalities in blood pressure (AOR = 1.76; 95% CI: 1.04-2.97; p = 0.034), abnormal consciousness (AOR = 10.41; 95% CI: 5.91-18.35; p < 0.001), dyspnea (AOR = 3.20; 95% CI: 1.72-5.96; p < 0.001), bronchorrhea (AOR = 1.99; 95% CI: 1.06-3.74; p = 0.032) and salivation (AOR = 2.70; 95% CI: 1.38-5.29; p = 0.004) were associated with higher odds of death. Symptomatic management was achieved through the administration of proton pump inhibitors (89.0%) and antidotes, such as pralidoxime (49.9%). The findings highlight the need for stricter regulation of organophosphate storage and sales, alongside community awareness campaigns. Establishing regional poison and antidote centers, ensuring early recognition of clinical manifestations, and implementing standardized management protocols may reduce mortality risk.

A key challenge in organophosphorus (OP) research is to develop efficient means to decrease OP levels after exposure. Scavenging, capturing, or degrading circulating OPs in vivo could minimize OP penetration into the brain and other organs, and decrease toxicity. OPs produce acute effects primarily through acetylcholinesterase (AChE) inhibition, leading to neurotoxic events. Current standard of care (SOC) for OP exposure includes the AChE reactivator 2-PAM as well as atropine, and midazolam or diazepam. However, SOC therapeutics only address AChE symptomatic toxicity but do not increase clearance. SOC does not degrade OPs. Using haptens designed employing transition state analogy, we procured and characterized monoclonal antibodies (mAbs) that, in the presence of 2-PAM, increased the hydrolysis of paraoxon (POX) and promoted degradation of nerve agent mimics. The ability of these novel antibodies to combine with 2-PAM and selectively recognize and degrade OPs suggests that they could provide a new approach to decrease OP-induced toxicity.

Nausea and vomiting in pregnancy is a common affliction, especially in the early trimesters. This is typically managed at home with doxylamine-pralidoxime or other home remedies. Many women, however, require additional adjuncts to control their symptoms. In this case we present a G2P0 female at 7 weeks gestation who arrived in the emergency department with persistent vomiting for several days. This patient already had a home medication regimen of multiple antiemetics. Additional treatment with ondansetron, prochlorperazine, and metoclopramide via IV administration as well as fluid administration resulted in minimal improvement in her symptoms in the emergency department. After stepwise escalation of antiemetic therapy and fluid resuscitation failed to provide relief, droperidol administration resulted in the rapid and complete resolution of her symptoms. This allowed for a safe discharge rather than admission for hyperemesis gravidarum. This case highlights the utility of droperidol as a rescue antiemetic in pregnancy when conventional therapies prove to be ineffective. This adds to the evidence supporting consideration of droperidol for refractory cases of nausea and vomiting and hyperemesis gravidarum in pregnancy. The purpose of this case report is to describe the safety and efficacy of droperidol in the treatment in refractory nausea and vomiting in pregnancy.

Organophosphorus compounds (OP), like pesticides and nerve agents, are potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) due to the phosphylation of their catalytic serine. Current treatment is limited, as approved oximes lack broad-spectrum efficacy and are poor reactivators of inhibited BChE. An alternative approach is pseudo-catalytic OP bioscavenging in which BChE and an efficient reactivator rapidly degrade OP in circulation, preventing it from reaching target tissues enriched with AChE. As imidazolium oximes were previously identified as potent BChE reactivators, we prepared eight novel N-substituted imidazolium oximes and tested them as reactivators of both human AChE and BChE inhibited by pesticide derivative paraoxon, and nerve warfare agents (sarin, cyclosarin, tabun VX, and five A-series agents). Oxime 3 (1,3-dibenzyl-2-hydroxy (imino)methylimidazolium bromide) was identified as the most potent reactivator, showing nanomolar affinity with native BChE and reactivation efficacy superior to standard oximes for cyclosarin-, sarin-, and tabun-BChE conjugate that was 1400-fold, 20-fold and 40-fold higher, respectively. In human whole blood, 30 μM cyclosarin was pseudo-catalytically decomposed by supplemented BChE and oxime 3, restoring 65% of total cholinesterase activity within 10 min. Although less potent, we identified two oximes capable of reactivating A-230-BChE conjugate. Furthermore, oxime 3 was not toxic to neural SH-SY5Y and hepatic HepG2 cells in concentrations relevant for biological activity. These findings highlight oxime 3 as well as the N,N'-dibenzyl imidazolium scaffold as the most potent BChE reactivators reported to date, providing a critical foundation for the advancement of bioscavenging-based therapies for OP poisoning.

Although acetylcholinesterase (AChE) is the primary inhibitory target for organophosphate (OP) insecticides and chemical warfare nerve agents, research supports the concept that the wide range of systems affected by OPs are not solely dependent on the anticholinesterase activity of OPs but are attributable to the inhibition of other serine hydrolases. Oxime reactivators play an integral role in the treatment of acute OP exposure by returning function to OP-inhibited AChE. Our laboratory has synthesized and patented a platform of oxime reactivators (US Patent 9,227,937) that have provided central neuroprotection through returning function to OP-inhibited AChE in the brain and preservation of neuronal and glial structures from damage in a rat model; the current US-approved oxime, pralidoxime, does not provide central neuroprotection. Thus, returning function to other OP-inhibited serine hydrolases by these novel oximes could provide additional secondary neuroprotection. Rat brain proteins were studied using activity-based protein profiling (ABPP) for serine hydrolase targets of a highly relevant sarin surrogate, nitrophenyl isopropyl methylphosphonate (NIMP), alone or in combination with Oxime 20, our lead novel AChE reactivator. ABPP indicated that NIMP significantly inhibited 6 serine hydrolases, and of these were the well-known serine hydrolases fatty acid amide hydrolase and monoacylglycerol lipase, which are important in endocannabinoid signaling. Oxime 20 administration after NIMP treatment showed only limited remediation of the inhibition experienced by these targets. The impact of this study is the identification of secondary serine esterase targets that could be explored for esterase reactivating therapeutics for the treatment of OP poisoning.