Evaluation of the effectiveness of fresh frozen plasma transfusion as adjuvant treatment in acute organophosphate-poisoned patients: A randomized clinical trial.

Organophosphorus (OP) poisoning is a significant cause of morbidity and mortality worldwide. Recent research has explored new approaches to improving treatment options, which present several challenges. This study aimed to evaluate the role of fresh frozen plasma (FFP) as an adjunctive therapy for acute OP intoxication. A prospective single-blinded randomized clinical trial was conducted on patients of both sexes admitted to the Intensive Care Unit (ICU) of the Poison Control Center at Ain Shams University Hospital (PCC-ASUH) with acute OP toxicity during the period from the beginning of August 2022 to the end of July 2023. According to the Peradeniya score, Group I consisted of 48 patients (52%) with moderate OP poisoning, and Group II consisted of 44 patients (48%) with severe OP poisoning. Patients in the moderate group were assigned to receive either standard treatment (Group Ia, n = 24) or standard treatment plus FFP (Group Ib, n = 24). In addition, patients in the severe group were assigned to receive either standard treatment (Group IIa, n = 22) or standard treatment plus FFP (Group IIb, n = 22). A total of 46 patients received FFP transfusion. The authors demonstrated that the early use of a total of nine packs of FFP (250 mL each) over three consecutive days significantly reduced the total doses of atropine and oximes, the total hospitalization period, and the requirement for mechanical ventilation in patients with OP poisoning, both in the moderate and severe groups.

The Insidious Enemy of the Liver: The Situation in Childhood Acetaminophen Poisoning and Early N-AC Treatment.

METHODS: This study was designed as a cross-sectional, observational, retrospective study. The variables of the study were paracetamol overdose, demographic information, poisoning mechanisms, clinical, laboratory findings, and clinical progression of the cases. The cases compared in whom treatment was initiated within the first 8 hours after poisoning and those in whom it was not. χ 2 , t test, and logistic regression analyses were conducted at appropriate facilities. RESULTS: Three hundred forty-eight cases were included in the study. N-AC treatment was initiated within the first 8 hours after poisoning in 322 cases (92.5%), and 26 cases received N-AC treatment after 8 hours after poisoning. Liver toxicity developed in 6 cases (1.7%), and indications for liver transplantation were met in 36 cases (10.3%). Among the 26 cases for which treatment was not initiated within the first 8 hours, 18 cases (69.2%) had indications for liver transplantation ( P < 0.01). It was found that N-AC within the first 8 hours reduced the risk by 43 times ( P = 0.02) and being older than 6 years, being admitted to the intensive care unit, and having alanine aminotransferase values above 1000 U/L increased the risk significantly ( P = 0.009, P = 0.005, P < 0.001). When a receiver operating characteristic curve was plotted for the 4th-hour blood acetaminophen level to predict liver transplantation, a value of 684.5 µg/mL emerged with 89% sensitivity and 93% specificity (area under the curve, 0.951). CONCLUSIONS: As a result, this study demonstrates the protective effect of early-initiated N-AC therapy on liver toxicity in pediatric acetaminophen poisoning cases. It also highlights a significant impact of gastrointestinal decontamination methods.

Medication error with methotrexate. / Feildosering av metotreksat.

Background: A woman in her seventies presented to the accident and emergency department (A&E) with shortness of breath that had increased over a period of three weeks. She had a history of COPD, hypertension and polymyalgia rheumatica. A medication error involving methotrexate, used for autoimmune diseases, was discovered during her medical history review. Case presentation: The patient arrived with stable vital signs, including 94 % oxygen saturation and a respiratory rate of 20 breaths/min. She had been taking 2.5 mg of methotrexate daily for the past three weeks instead of the prescribed weekly dose of 15 mg. Other examinations revealed no alarming findings, except for a slightly elevated D-dimer level. Interpretation: Considering her medical history and exclusion of other differential diagnoses, methotrexate toxicity was suspected. The patient was admitted to the hospital and intravenous folinic acid was initiated as an antidote treatment. Five days later, the patient was discharged with an improvement in the shortness of breath. This case underscores the importance of effective communication in health care, particularly in complex cases like this, where understanding dosages and administration is crucial. Medical history, clinical examinations and medication reviews, often involving clinical pharmacists, are vital in the A&E to reveal medication errors.

Cyanide toxicity secondary to apricot (Prunus armeniaca) kernel meal ingestion in a canine.

Cyanide is one of the most rapidly acting, lethal poisons in human and veterinary medicine. This case report discusses a novel case of cyanide toxicity from apricot (Prunus armeniaca) kernel ingestion in a canine and alternative treatment modalities. A 9.5-year-old female spayed Golden Retriever presented for vomiting and collapse after ingestion of apricot kernel meal. Laboratory findings, including a high anion gap metabolic acidosis with severe hyperlactatemia, clinical signs, and known ingestion of apricot kernels, were suggestive of cyanide toxicity. The dog was treated with crystalloid and synthetic colloids for stabilization and antidote therapy with hydroxocobalamin. The dog's metabolic acidosis and hyperlactemia worsened despite antidote therapy, and the dog progressed to CPA during gastric decontamination efforts. The dog did not respond to CPR efforts. This report will review the mechanism of cyanide toxicity, treatment options, and considerations for future cases.

Preferential Door for Ligand Binding and Unbinding Pathways in Inhibited Human Acetylcholinesterase.

Rising global population and increased food demands have resulted in the increased use of organophosphate pesticides (OPs), leading to toxin accumulation and transmission to humans. Pralidoxime (2-PAM), an FDA-approved drug, serves as an antidote for OP therapy. However, the atomic-level detoxification mechanisms regarding the design of novel antidotes remain unclear. This is the first study to examine the binding and unbinding pathways of 2-PAM to human acetylcholinesterase (HuAChE) through three identified doors using an enhanced sampling method called ligand-binding parallel cascade selection molecular dynamics (LB-PaCS-MD). Remarkably, LB-PaCS-MD could identify a predominant in-line binding mechanism through the acyl door at 63.79% ± 6.83%, also implicating it in a potential unbinding route (90.14% ± 4.22%). Interestingly, crucial conformational shifts in key residues, W86, Y341, and Y449, and the Ω loop significantly affect door dynamics and ligand binding modes. The LB-PaCS-MD technique can study ligand-binding pathways, thereby contributing to the design of antidotes and covalent drugs.

Antidote-controlled DNA aptamer modulates human factor IXa activity.

Thrombosis leads to elevated mortality rates and substantial medical expenses worldwide. Human factor IXa (HFIXa) protease is pivotal in tissue factor (TF)-mediated thrombin generation, and represents a promising target for anticoagulant therapy. We herein isolated novel DNA aptamers that specifically bind to HFIXa through systematic evolution of ligands by exponential enrichment (SELEX) method. We identified two distinct aptamers, seq 5 and seq 11, which demonstrated high binding affinity to HFIXa (Kd = 74.07 ± 2.53 nM, and 4.93 ± 0.15 nM, respectively). Computer software was used for conformational simulation and kinetic analysis of DNA aptamers and HFIXa binding. These aptamers dose-dependently prolonged activated partial thromboplastin time (aPTT) in plasma. We further rationally optimized the aptamers by truncation and site-directed mutation, and generated the truncated forms (Seq 5-1t, Seq 11-1t) and truncated-mutated forms (Seq 5-2tm, Seq 11-2tm). They also showed good anticoagulant effects. The rationally and structurally designed antidotes (seq 5-2b and seq 11-2b) were competitively bound to the DNA aptamers and effectively reversed the anticoagulant effect. This strategy provides DNA aptamer drug-antidote pair with effective anticoagulation and rapid reversal, developing advanced therapies by safe, regulatable aptamer drug-antidote pair.

Cholesterol Oxime Olesoxime Assessed as a Potential Ligand of Human Cholinesterases.

Olesoxime, a cholesterol derivative with an oxime group, possesses the ability to cross the blood-brain barrier, and has demonstrated excellent safety and tolerability properties in clinical research. These characteristics indicate it may serve as a centrally active ligand of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), whose disruption of activity with organophosphate compounds (OP) leads to uncontrolled excitation and potentially life-threatening symptoms. To evaluate olesoxime as a binding ligand and reactivator of human AChE and BChE, we conducted in vitro kinetic studies with the active metabolite of insecticide parathion, paraoxon, and the warfare nerve agents sarin, cyclosarin, tabun, and VX. Our results showed that both enzymes possessed a binding affinity for olesoxime in the mid-micromolar range, higher than the antidotes in use (i.e., 2-PAM, HI-6, etc.). While olesoxime showed a weak ability to reactivate AChE, cyclosarin-inhibited BChE was reactivated with an overall reactivation rate constant comparable to that of standard oxime HI-6. Moreover, in combination with the oxime 2-PAM, the reactivation maximum increased by 10-30% for cyclosarin- and sarin-inhibited BChE. Molecular modeling revealed productive interactions between olesoxime and BChE, highlighting olesoxime as a potentially BChE-targeted therapy. Moreover, it might be added to OP poisoning treatment to increase the efficacy of BChE reactivation, and its cholesterol scaffold could provide a basis for the development of novel oxime antidotes.

Acute arsenic exposure secondary to deliberate self-poisoning with sheep dip.

A 53-year-old male patient presented to a regional hospital Emergency Department approximately 2 h post an intentional ingestion of Coopers Instant Wetting Powder Sheep Dip (66% arsenic trioxide, 23% sulphur and 0.42% rotenone), mixed in 600 mL water, as a suicide attempt. On arrival to the Emergency Department, the patient had nausea, vomiting and diarrhoea. Seven hours post ingestion, hypotension developed (BP 90/60 mmHg) and intravenous fluids were commenced. He later developed QTc prolongation. He was treated with 2,3-Dimercapto-1-propanesulfonic acid (DMPS) and N-acetylcysteine and improved without development of neurology. Further investigation of NAC efficacy in humans in the setting of acute arsenic poisoning is required and the optimal duration of treatment and dosing needs to be established. This case highlights an uncommon poisoning which presented to the Emergency Department, the acute symptoms of arsenic toxicity and considerations for management.

A functional RNA-origami as direct thrombin inhibitor with fast-acting and specific single-molecule reversal agents in vivo model.

Injectable anticoagulants are widely used in medical procedures to prevent unwanted blood clotting. However, many lack safe, effective reversal agents. Here, we present new data on a previously described RNA origami-based, direct thrombin inhibitor (HEX01). We describe a new, fast-acting, specific, single-molecule reversal agent (antidote) and present in vivo data for the first time, including efficacy, reversibility, preliminary safety, and initial biodistribution studies. HEX01 contains multiple thrombin-binding aptamers appended on an RNA origami. It exhibits excellent anticoagulation activity in vitro and in vivo. The new single-molecule, DNA antidote (HEX02) reverses anticoagulation activity of HEX01 in human plasma within 30 s in vitro and functions effectively in a murine liver laceration model. Biodistribution studies of HEX01 in whole mice using ex vivo imaging show accumulation mainly in the liver over 24 h and with 10-fold lower concentrations in the kidneys. Additionally, we show that the HEX01/HEX02 system is non-cytotoxic to epithelial cell lines and non-hemolytic in vitro. Furthermore, we found no serum cytokine response to HEX01/HEX02 in a murine model. HEX01 and HEX02 represent a safe and effective coagulation control system with a fast-acting, specific reversal agent showing promise for potential drug development.

Does Mixing Activated Charcoal With Cola Improve Tolerability Without Affecting Pharmacokinetics? A Randomized Controlled Crossover Trial.

INTRODUCTION: Activated charcoal is the most common form of gastrointestinal decontamination used for the poisoned patient. One limitation to its use is patient tolerability due to palatability. Some recommend mixing activated charcoal with cola to improve palatability. An important question is whether mixing activated charcoal with cola affects the ability of the activated charcoal to adsorb xenobiotic. METHODS: This was a prospective randomized controlled crossover trial. Five healthy adults aged 18 to 40 years were recruited. Participants received 45 mg/kg acetaminophen rounded down to the nearest whole tablet. One hour later, they were randomized to receive 50 g of an activated charcoal-water premixture alone or mixed with cola. Acetaminophen levels were collected. The area under the curve of acetaminophen concentrations over time was measured as a marker for degree of absorption. Participants also completed an appeal questionnaire in which they rated the activated charcoal preparations. Participants would then return after at least 7 days to repeat the study with the other activated charcoal preparation. RESULTS: Four male participants and 1 female participant were recruited. There was no statistical difference in preference score for activated charcoal alone versus the cola-activated charcoal mixture. There was no statistical difference in the area under the curve of acetaminophen concentrations over time between activated charcoal alone and the cola-activated charcoal mixture. Of note, the study is limited by the small sample size, limiting its statistical power. DISCUSSION: The absorption of acetaminophen in an overdose model is no different when participants received activated charcoal alone or a cola-activated charcoal mixture as suggested by area under the curve. In this small study, there was no difference in preference for activated charcoal alone or a cola-activated charcoal mixture across a range of palatability questions. On an individual level, some participants preferred the activated charcoal-cola mixture, and some preferred the activated charcoal alone.

A hospital management algorithm for acute poisoning by Paraquat® in a pediatric population, a series of cases / Algoritmo de manejo hospitalario para la intoxicación aguda por Paraquat® en población pediátrica, serie de casos.

Paraquat®, or N,N'-dimethyl-4,4'-bipyridinium dichloride, is a bipyridyl compound used as a non-selective herbicide and desiccant that can cause acute poisoning through all routes of exposure. There is no known antidote, and the available treatments are based on avoiding its absorption and timely removing it, in adults and children. We describe a case series of 14 pediatric patients from the department of Cauca, Colombia, with acute intoxication after oral intake of paraquat. Patients were referred to a medium-high complexity hospital in southwestern Colombia and treated according to an institutional protocol for acute paraquat poisoning. Acute paraquat poisoning after oral ingestion is associated with a high mortality rate, even with timely medical attention, as the compound has no known antidote and quickly reaches systemic concentrations for fulminant poisoning. Based on the available literature, our center has proposed a clinical protocol including early standard management, immunosuppressive and antioxidant treatments, and systemic removal techniques. This protocol suggests an adequate approach to acute paraquat poisoning in the pediatric population.

El dicloruro de 1,1'-dimetil-4,4'-bipiridilo (Paraquat®) es un compuesto químico de la familia de las piridinas, utilizado como herbicida no selectivo y desecante. Este compuesto puede causar intoxicación aguda por todas las vías de exposición. En el momento, no hay un antídoto conocido y los tratamientos disponibles, incluidos los pediátricos, se basan en contrarrestar su absorción y propiciar su remoción oportuna. Se describe una serie de casos de 14 pacientes pediátricos, procedentes en su mayoría del departamento del Cauca, con intoxicación aguda por ingestión de paraquat. Los pacientes fueron remitidos y atendidos en un hospital de mediana a alta complejidad en el suroccidente colombiano, con un protocolo institucional para el manejo de la intoxicación aguda por el herbicida. La intoxicación aguda con paraquat por vía oral se asocia con una alta tasa de mortalidad, aún con atención médica oportuna, pues fácilmente se alcanzan concentraciones sistémicas para ser fulminante. Basado en la literatura disponible, el Hospital Universitario San José ha propuesto un protocolo clínico ­adecuado para la intoxicación aguda por paraquat en población pediátrica­ que incluye manejo estándar temprano, tratamiento inmunosupresor y antioxidante, y técnicas para su remoción sistémica.

An approach to the management of acute poisoning in emergency settings.

The impact of poisoning can differ significantly depending on the specific substance consumed. Identifying toxic substances in a patient is crucial to obtaining a thorough medical history. Frontline healthcare providers in the emergency department often handle patients presenting with poisoning. Their clinical presentation can vary depending on their dose, duration of exposure, and pre-existing medical conditions. Initially, poisoning management entails administering supportive care such as absorption and enhancing the elimination of poison with charcoal and antidote administration after identifying the poisoning substances. This article aims to provide a basic overview of the concepts involved in evaluating and managing these individuals.

Polyvinyl chloride solvent cement poisoning: a case report.

BACKGROUND: S-lon® (S) is a locally produced polyvinyl chloride-based solvent cement. It is a clear, slightly viscous liquid. Other constituents include 1-cyclohexanone, 3-butanone, and 1-acetone. It is used ubiquitously for building construction in Sri Lanka. Although the clinical effects of the compound have not yet been ascertained, the constituents have been implicated in neurotoxicity, respiratory tract, eye and skin irritation, and delayed liver and renal injury. CASE DESCRIPTION: A 42-year-old South Asian male presented following self-ingestion of S. His vital parameters were stable and initially managed symptomatically. A few hours later, he developed central nervous system depression and stridor requiring elective intubation. Examination of the upper airway revealed inflammation and edema. He was sedated and ventilated, and intravenous dexamethasone was administered. Attempts at removal of the nasogastric tube after extubation on day 3 failed. The patient had to be reintubated and sedated owing to extreme agitation not responding to routine doses of sedatives. The nasogastric tube had been amalgamated after reacting with S, forming a solid clump, later found after removal. The posterior pharynx and nasopharynx were packed and later removed before extubation. The patient made a full recovery and was transferred to the ward on day 5. CONCLUSION: Ingestion of a sufficient quantity of S could result in gut absorption with central nervous system depression, coma, and even death. No antidote is available for toxicity, and management is largely supportive. As witnessed in our patient, chemical laryngitis and upper airway inflammation may lead to upper airway obstruction. Chemical reactions with medical equipment may lead to unforeseen outcomes.

The risk associated with organophosphorus nerve agents: from their discovery to their unavoidable threat, current medical countermeasures and perspectives.

The first organophosphorus nerve agent was discovered accidently during the development of pesticides, shortly after the first use of chemical weapons (chlorine, phosgene) on the battlefield during World War I. Despite the Chemical Weapons Convention banning these substances, they have still been employed in wars, terrorist attacks or political assassinations. Characterised by their high lethality, they target the nervous system by inhibiting the acetylcholinesterase (AChE) enzyme, preventing neurotransmission, which, if not treated rapidly, inevitably leads to serious injury or the death of the person intoxicated. The limited efficacy of current antidotes, known as AChE reactivators, pushes research towards new treatments. Numerous paths have been explored, from modifying the original pyridinium oximes to developing hybrid reactivators seeking a better affinity for the inhibited AChE. Another crucial approach resides in molecules more prone to cross the blood-brain barrier: uncharged compounds, bio-conjugated reactivators or innovative formulations. Our aim is to raise awareness on the threat and toxicity of organophosphorus nerve agents and to present the main synthetic efforts deployed since the first AChE reactivator, to tackle the task of efficiently treating victims of these chemical warfare agents.

Is there a role for the laboratory monitoring in the management of specific antidotes of direct oral anticoagulants?

Given the growing number of patients receiving direct oral anticoagulant (DOAC), patients requiring rapid neutralization is also increasing in case of major bleedings or urgent surgery/procedures. Idarucizumab is commercialized as a specific antidote to dabigatran while andexanet alfa has gained the Food and Drug Administration and the European Medicines Agency approval as an oral anti-factor Xa inhibitors antidote. Other antidotes or hemostatic agents are still under preclinical or clinical development, the most advanced being ciraparantag. DOAC plasma levels measurement allows to appropriately select patient for antidote administration and may prevent unnecessary prescription of expensive molecules in some acute clinical settings. However, these tests might be inconclusive after some antidote administration, namely andexanet alfa and ciraparantag. The benefit of laboratory monitoring following DOAC reversal remains unclear. Here, we sought to provide an overview of the key studies evaluating the safety and efficacy of DOAC reversal using the most developed/commercialized specific antidotes, to discuss the potential role of the laboratory monitoring in the management of patients receiving DOAC specific antidotes and to highlight the areas that deserve further investigations in order to establish the exact role of laboratory monitoring in the appropriate management of DOAC specific antidotes.

Pediatric Medical Countermeasures: Antidotes and Cytokines for Radiological and Nuclear Incidents and Terrorism.

The war in Ukraine raises concerns for potential hazards of radiological and nuclear incidents. Children are particularly vulnerable in these incidents and may need pharmaceutical countermeasures, including antidotes and cytokines. Searches found no published study comparing pediatric indications and dosing among standard references detailing pediatric medications for these incidents. This study addresses this gap by collecting, tabulating, and disseminating this information to healthcare professionals caring for children. Expert consensus chose the following references to compare their pediatric indications and dosing of medical countermeasures for radiation exposure and internal contamination with radioactive materials: Advanced Hazmat Life Support (AHLS) for Radiological Incidents and Terrorism, DailyMed, Internal Contamination Clinical Reference, Medical Aspects of Radiation Incidents, and Medical Management of Radiological Casualties, as well as Micromedex, POISINDEX, and Radiation Emergency Medical Management (REMM). This is the first study comparing pediatric indications and dosing for medical countermeasures among commonly used references for radiological and nuclear incidents.

Acute liver failure.

ABSTRACT: Acute liver failure, commonly caused by acetaminophen overdose, is associated with numerous systemic complications including cerebral edema, hypotension, acute kidney injury, and infection. Management is primarily supportive, with an emphasis on excellent neurocritical care. Although some antidotes and targeted treatments exist, the only definitive treatment remains orthotopic liver transplant.

Surfactant-based supramolecular dye assembly: A highly selective and economically viable platform for quantification of heparin antidote.

Herein, we have employed a supramolecular assembly of a cationic dye, LDS-698 and a common surfactant sodium dodecyl sulfate (SDS) as a turn-on fluorescent sensor for protamine (Pr) detection. Addition of cationic Pr to the solution of dye-surfactant complex brings negatively charged SDS molecules together through strong electrostatic interaction, assisting aggregation of SDS way before its critical micellar concentration (CMC). These aggregates encapsulate the dye molecules within their hydrophobic region, arresting non-radiative decay channels of the excited dye. Thus, the LDS-698•SDS assembly displays substantial enhancement in fluorescence intensity that follows a nice linear trend with Pr concentration, providing limit of detection (LOD) for Pr as low as 3.84(±0.11) nM in buffer, 124.4(±6.7) nM in 1% human serum and 28.3(±0.5) nM in 100% human urine. Furthermore, high selectivity, low background signal, large stokes shift, and emission in the biologically favorable deep-red region make the studied assembly a promising platform for Pr sensing. As of our knowledge it is the first ever Pr sensory platform, using a very common surfactant (SDS), which is economically affordable and very easily available in the market. This innovative approach can replace the expensive, exotic and specialized chemicals considered for the purpose and thus showcase its potential in practical applications.

Assessing the impact of a new medical toxicology service on the treatment of paracetamol overdose at a large tertiary care hospital.

BACKGROUND: Paracetamol overdose is the most common cause of acute liver failure in the United States. Administration of acetylcysteine is the standard of care for this intoxication. Laboratory values and clinical criteria are used to guide treatment duration, but decision-making is nuanced and often complex and difficult. The purpose of this study was to evaluate the effect of the introduction of a medical toxicology service on the rate of errors in the management of paracetamol overdose. METHODS: This was a single center, retrospective, cohort evaluation. Patients with suspected paracetamol overdose were divided into two groups: those attending in the 1 year period before and those in the 1 year after the introduction of the medical toxicology service. The primary outcome was the frequency of deviations from the established management of paracetamol intoxication, using international guidelines as a reference. RESULTS: Fifty-four patients were eligible for the study (20 pre-toxicology-service, 34 post-toxicology-service). The frequency of incorrect therapeutic decisions was significantly lower in the post-toxicology service implementation versus the pre-implementation group (P = 0.005). DISCUSSION: Our study suggests that a medical toxicology service reduces the incidence of management errors, including the number of missed acetylcysteine doses in patients with paracetamol overdose. The limitations include the retrospective study design and that the study was conducted at a single center, which may limit generalizability. CONCLUSIONS: The implementation of a medical toxicology service was associated with a decrease in the number of errors in the management of paracetamol overdose.

Uncharged mono- and bisoximes: In search of a zwitterion to countermeasure organophosphorus intoxication.

The current study imposes a new class of organophosphorus (OP)-inhibited cholinesterase reactivators by conceptualizing a family of asymmetric bisoximes with various reactivating scaffolds. Several novel nucleophilic warheads were investigated, putting forward 29 novel reactivating options, by evaluating their nucleophilicity and ability to directly decompose OP compounds. Adopting the so-called zwitterionic strategy, 17 mono-oxime and nine bisoxime reactivators were discovered with major emphasis on the bifunctional-moiety approach. Compounds were compared with clinically used standards and other known experimentally highlighted reactivators. Our results clearly favor the concept of asymmetric bisoximes as leading reactivators in terms of efficacy and versatility. These top-ranked compounds were characterized in detail by reactivation kinetics parameters and evaluated for potential CNS availability. The highlighted molecules 55, 57, and 58 with various reactivating warheads, surpassed the reactivating potency of pralidoxime and several notable uncharged reactivators. The versatility of lead drug candidate 55 was also inspected on OP-inhibited butyrylcholinesterase, revealing a much higher rate compared to existing clinical antidotes.