Common Antidote Research Articles

Pharmacological prophylaxis with pyridostigmine bromide against nerve agents adversely impact on airway function in an ex vivo rat precision-cut lung slice model

The carbamate pyridostigmine bromide (PB) is the only fielded pharmacological prophylaxis for military use against nerve agents. Previous studies have shown differences in the PB-pretreatment efficacy for various nerve agents and in the influence of post-exposure treatment with common antidotes. In the present study, the aim was to evaluate the possibility of using an ex vivo rat precision-cut lung slice model to determine the impact of PB pretreatment on VX-induced bronchoconstriction. In addition, the efficacy of post-exposure treatment with atropine sulfate following PB-prophylaxis was investigated. Bronchoconstriction was induced by electric-field stimulation and was significantly aggravated by 10 µM PB. Airway recovery was decreased by both 1 and 10 µM PB. Evaluation of acetylcholineesterese inhibition by PB showed that the lower concentration met the clinical criteria of residual enzyme activity while the higher concentration completely inhibited the activity. Exposure to VX with or without pretreatment demonstrated similar contractions. However, VX-incubation following pretreatment caused decreased airway relaxation compared to pretreatment alone. Atropine treatment following PB- and VX-exposure significantly decreased the maximum airway contraction and increased the relaxation. In conclusion, no beneficial effect of PB-prophylaxis on VX-induced contractions was observed. The atropine efficacy to relax airways was significant demonstrating the importance of efficient post-exposure therapeutics to protect against the life-threatening respiratory contractions.

CONCEPT OF ANTIDOTES V/S PRATIVISHA IN AYURVEDA - A REVIEW ARTICLE

Ayurveda is a traditional system of medicine with historical roots in the Indian subcontinent. It is one of the most technical medical systems in the world with an extended record of scientific experience. Ayurveda tells the way of life and how to live healthily and stay happy. It has eight prime branches of medicine. Agada tantra is one of the specialized divisions of Ayurveda that offer scrupulously thorough information about animate and non-animated poisons and methods of removal of these poisons from the body. It chiefly advocates different antidotes for equip- ment that are poisonous to the human body. There are various ancient books which have relation regarding the Toxicology Agada tantra in which we can get references regarding the above mentioned and treated as such with Antidotes. Antidotes are the substances used to counteract or deactivate the effects of poison. Poison may be by plant, or through animal bites like snake bites etc., agricultural poisons, poisonous metals and minerals etc. There are mainly two types of poison mentioned in Ayurveda, are Sthavar visha and Jangham visha., Common antidote in Ayurveda is Swarna, Ghrita, Godudha and Madhu etc. antidote plays important role in the treatment of poisoning which we can see in the current paper, the main moto of doctor is to save the patient's life. In Ayurveda, our Achar- yas mentioned the different types of poisonous substances and their antidote under Visha Chikitsa references. The concept of Prativisha which is existed since ancient time needs to be supplemented, explained, refurbish and narrate for proper treatment. So, this article aims to collect the references of curative and preventive measures of poisoning. Keywords: Visha, Antidotes, Vagbhatta, Vishavaidyajyotsnika

Beyond city limits: infrastructural regionalism in rural Montana, USA

ABSTRACT Regional infrastructures are a main object of governance questions in urban contexts, yet similar phenomena in rural areas are underexplored. Rural public institutions serve small populations dispersed across large geographical areas, making regional collaborations a common antidote to inherent challenges in rural governance. This paper engages with the nascent dialogue surrounding infrastructural regionalism to interpret the governance and political dimensions of the regional approach to rural infrastructure development. We use qualitative methods to analyse a rural regional water system in Montana, USA, that will deliver drinking water across a 31,000 km2 agricultural region via 480 km of networked pipelines. We find two key characteristics of the institution’s rural context and regional scope are in tension, leaving the geographical extent of the pipeline, and ultimately the spatiality of the region, uncertain. Namely, a set of centrifugal forces that result from unruly hyperlocal politics contrast a centripetal energy that results from the process of building the political capital needed to make the project possible. By revealing the unique governance pressures facing rural regional infrastructure governance, we counterbalance the urban bias in infrastructure and regional studies and contribute to ongoing debates in rural policy and public service provision.

Examination of the Efficacy and Cross-Reactivity of a Novel Polyclonal Antibody Targeting the Disintegrin Domain in SVMPs to Neutralize Snake Venom.

Snake envenomation can result in hemorrhage, local necrosis, swelling, and if not treated properly can lead to adverse systemic effects such as coagulopathy, nephrotoxicity, neurotoxicity, and cardiotoxicity, which can result in death. As such, snake venom metalloproteinases (SVMPs) and disintegrins are two toxic components that contribute to hemorrhage and interfere with the hemostatic system. Administration of a commercial antivenom is the common antidote to treat snake envenomation, but the high-cost, lack of efficacy, side effects, and limited availability, necessitates the development of new strategies and approaches for therapeutic treatments. Herein, we describe the neutralization ability of anti-disintegrin polyclonal antibody on the activities of isolated disintegrins, P-II/P-III SVMPs, and crude venoms. Our results show disintegrin activity on platelet aggregation in whole blood and the migration of the SK-Mel-28 cells that can be neutralized with anti-disintegrin polyclonal antibody. We characterized a SVMP and found that anti-disintegrin was also able to inhibit its activity in an in vitro proteolytic assay. Moreover, we found that anti-disintegrin could neutralize the proteolytic and hemorrhagic activities from crude Crotalus atrox venom. Our results suggest that anti-disintegrin polyclonal antibodies have the potential for a targeted approach to neutralize SVMPs in the treatment of snakebite envenomations.

Common antidotes used in the ICU

In Brief When ingested, some common household products can be poisonous, and, when taken improperly, both prescription and over-the-counter medications can result in overdoses. This article describes several common toxicities encountered in the ICU and their respective antidotes. When ingested, some common household products can be poisonous, and, when taken improperly, both prescription and over-the-counter medications can result in overdoses. This article describes several common toxicities encountered in the ICU and their respective antidotes.

A synthetic heparin mimetic that allosterically inhibits factor XIa and reduces thrombosis in vivo without enhanced risk of bleeding

BackgroundHuman factor XIa (FXIa) is an actively pursued target for development of safer anticoagulants. Our long‐standing hypothesis has been that allosterism originating from heparin‐binding site(s) on coagulation enzymes is a promising approach to yield safer agents. ObjectivesTo develop a synthetic heparin mimetic as an inhibitor of FXIa so as to reduce clot formation in vivo but not carry high bleeding risk. MethodsWe employed a gamut of methods involving synthetic chemistry, biophysical biochemistry, enzyme assays, blood and plasma coagulation assays, and in vivo thrombosis models in this work. ResultsSulfated chiro‐inositol (SCI), a non‐saccharide mimetic of heparin, was synthesized in three steps in overall yields of >50%. SCI inhibited FXIa with potency of 280 nmol/L and preferentially engaged FXIa's heparin‐binding site to conformationally alter its active site. SCI inhibition of FXIa could be rapidly reversed by common antidotes, such as protamine. SCI preferentially prolonged plasma clotting initiated with recalcification, rather than thromboplastin, alluding to its intrinsic pathway‐based mechanism. Human blood thromboelastography indicated good ex vivo anticoagulation properties of SCI. Rat tail bleeding and maximum‐dose‐tolerated studies indicated that no major bleeding or toxicity concerns for SCI suggesting a potentially safer anticoagulation outcome. FeCl3‐induced arterial and thromboplastin‐induced venous thrombosis model studies in the rat showed reduced thrombus formation by SCI at 250 μg/animal, which matched enoxaparin at 2500 μg/animal. ConclusionsOverall, SCI is a highly promising, allosteric inhibitor of FXIa that induces potent anticoagulation in vivo. Further studies are necessary to assess SCI in animal models mimicking human clinical indications.

Pralidoxime administered during cardiopulmonary resuscitation facilitates successful resuscitation in a pig model of cardiac arrest.

Pralidoxime is a common antidote for organophosphate poisoning; however, studies have also reported pralidoxime's pressor effect, which may facilitate the restoration of spontaneous circulation (ROSC) after cardiac arrest by improving coronary perfusion pressure (CPP). We investigated the immediate cardiovascular effects of pralidoxime in anaesthetised normal rats and the effects of pralidoxime administration during cardiopulmonary resuscitation (CPR) in a pig model of cardiac arrest. To evaluate the immediate cardiovascular effects of pralidoxime, seven anaesthetised normal rats received saline or pralidoxime (20mg/kg) in a randomised crossover design, and the responses were determined using the conductance catheter technique. To evaluate the effects of pralidoxime administration during CPR, 22 pigs randomly received either 80mg/kg of pralidoxime or an equivalent volume of saline during CPR. In the rats, pralidoxime significantly increased arterial pressure than saline (P=.044). The peak effect on arterial pressure was observed in the first minute. In a pig model of cardiac arrest, CPP during CPR was higher in the pralidoxime group than in the control group (P=.002). ROSC was attained in three animals (27.3%) in the control group and nine animals (81.8%) in the pralidoxime group (P=.010). Three animals (27.3%) in the control group and eight animals (72.2%) in the pralidoxime group survived the 6-hour period (P=.033). In conclusion, pralidoxime had a rapid onset of pressor effect. Pralidoxime administered during CPR led to significantly higher rates of ROSC and 6-hour survival by improving CPP in a pig model.

A Common Antidote for an Uncommon Indication.

A Common Antidote for an Uncommon Indication.

A CASE OF DAPSONE-INDUCED METHEMOGLOBINEMIA

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Dapsone is an antibiotic used with relative frequency for dermatological illnesses and opportunistic infection prophylaxis. A known complication of this drug is methemoglobinemia, a condition that can be both difficult to identify and potentially fatal. Here we present the case of a patient diagnosed with and treated for dapsone-induced methemoglobinemia. CASE PRESENTATION: A 40-year-old Caucasian female with a history of depression complicated by past suicide attempt and chronic autoimmune urticaria treated with dapsone presented to the emergency department with suicidal ideation. She reported taking 45 pills of 100mg dapsone and 27 pills of 300mg gabapentin prior to arrival. Physical exam was remarkable for cyanosis noted in the perioral area. Her initial course was complicated by oxygen desaturation to 83% with no identified pulmonary process. She was found to have methemoglobinemia with initial methemoglobin level of 39.9% on VBG. She was treated with 50mg IV methylene blue in the Emergency Department then transferred to the Intensive Care Unit. Throughout her admission, she was given a total of 300mg IV methylene blue with eventual resolution of methemoglobinemia and symptoms. DISCUSSION: Acquired methemoglobinemia is thought to be due exposure to oxidizing agents such as dapsone and other commonly used medications. These agents accelerate the oxidization of hemoglobin at a rate that overwhelms endogenous reduction capacities. This results in an inability of hemoglobin to bind oxygen, ultimately leading to reduced oxygen delivery throughout the body and diffuse tissue hypoxia. Methylene blue, a common antidote to methemoglobinemia, works within the NADH-Methemoglobin reductase system to reduce methemoglobin to hemoglobin. Clinically, cyanosis resistant to oxygen therapy will typically occur at methemoglobin levels of 15% or higher. As methemoglobin levels increase, symptoms such as headache, fatigue and tachycardia become more common. Arrhythmias, seizures and coma typically occur at levels above 60%, with death possible over 70%. Diagnosis of methemoglobinemia can be somewhat challenging and requires a degree of clinical suspicion. Standard pulse oximetry does not detect methemoglobin and can reflect a falsely elevated or falsely decreased oxygen saturation depending on concentration. Co-oximetry can help with diagnosis but is not as definitive as arterial blood gas in the hospital setting. Patients diagnosed with methemoglobinemia should be treated with high-dose oxygen as well as methylene blue for fractions greater than 30% or symptomatic hypoxia. For patients with G6PD deficiency, however, methylene blue is contraindicated. Hyperbaric oxygen and exchange transfusions are safe alternatives and useful for severe or refractory cases. CONCLUSIONS: Methemoglobinemia is a potentially life-threatening condition. Clinicians should be aware of the signs, symptoms and treatment options. Reference #1: Pereira, R.O. and Costa, J., 2008. Methemoglobinemia: from diagnosis to treatment. Revista brasileira de anestesiologia, 58(6), pp.651-664. Reference #2: Longo, D. and Fauci, A., 2013. Poisoning and drug overdose. Harrison's manual of medicine. (pp. 177). McGraw Hill Professional. Reference #3: Marino, P. (2014). Oximetry and capnometry. The ICU Book (pp. 409-413). Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams & Wilkins. DISCLOSURES: No relevant relationships by Abigail Go, source=Web Response No relevant relationships by Stephen Osmon, source=Web Response No relevant relationships by Maria Srour, source=Web Response

Analysis of the Safety Profile of Commonly Used Procoagulants Using the FDA Adverse Event Reporting System

Introduction:Though less commonly used than their anticoagulant counterparts, procoagulants have an important role in the reversal of anticoagulation. Four-factor prothrombin complex concentrate (4PCC) is now approved by the U.S. Food & Drug Administration (FDA) for the reversal of major bleeding associated with warfarin, and is often used off-label to reverse direct oral anticoagulants. Three-factor concentrate (3PCC) and off-label use of recombinant activated factor VII (rFVIIa) have filled this role in the past. Vitamin K is also used as a common antidote for warfarin-induced coagulopathy. Comparative data evaluating the safety profiles and relative thrombotic risks of the PCCs and rFVIIa is limited. In order to better evaluate their comparative safety we calculated the rate of adverse events reported to the FDA of each procoagulant.Methods:We evaluated the FDA Adverse Event Reporting System (FAERS) database, which compiles drug-related adverse events reported to the FDA from 1969 onwards, to assess the rate of adverse events reported with various procoagulants. Safety profiles were assessed using proportional reporting ratios (PRR) with the total number of reported cases as the denominator. Adverse events data for each drug (vitamin K, rFVIIa, 3PCC, 4PCC) was gathered from FAERS. Both generic and brand names were used to query the database. Adverse events data was filtered by including only events reported by healthcare professionals. Specific adverse events were chosen apriori based on hypothesized potential complications and included hemorrhagic and thrombotic complications. The PRR with 95% confidence interval was generated for each event, with a cut-off of 2 being used to identify associations.Results:As shown in Table 1 and Figure 1, rFVIIa was associated with increased reports of mortality while 4PCC was associated with ischemic stroke, and all but rFVIIa were associated with high INR. 3PCC displayed an increased association with reports of intracranial hemorrhage (ICH), although there was a low rate of reports for 3PCC. Lesser associations were found between rFVIIa and myocardial infarction (MI), 3PCC and deep-vein thrombosis (DVT), and 4PCC and DVT and ICH. In general, vitamin K had the weakest associations among adverse events.Conclusions:Our analysis found that the rate of reports of death and MI were higher with rFVIIa than other procoagulants, while reports of ischemic stroke and intracranial hemorrhage were more common with PCCs. rFVIIa has been associated with cardiovascular before, a finding reiterated by our study. There are notable limitations of this type of analysis, including the reliance on the accurate reporting of adverse events to the FDA, possibility of duplications of reports in the FAERS database, and the importance of not conflating correlation with causation as it relates to these events. The association between rFVIIa and increased death may be due to rFVIIa's history of off-label use in trauma patients and other patient groups at higher risk for mortality. While 4PCC may be the procoagulant of the present, it does not have a perfect safety profile, and further study is needed to better characterize the complications of 4PCC and ensure that it is used in such a way as to not under- or over-treat the condition. DisclosuresNo relevant conflicts of interest to declare.

The Current State of Poison Control Centers in Pakistan and the Need for Capacity Building.

Chemical exposure is a major health problem globally. Poison control centers (PCCs) play a leading role both in developed and developing countries in the prevention and control of poisonous chemical exposures. In this study, we aimed to assess the current state of PCCs in Pakistan and highlight capacity building needs in these centers. A cross-sectional survey of the two registered PCCs was done during August - December 2011. Necessary services of the PCCs were evaluated and the data were recorded on a predesigned checklist. Both PCCs are affiliated to a tertiary care hospital. Clinical services to poisoned patients were available 24 hours a day / 7 days a week. Information on common local products was available to poison center staff. Both centers were involved in undergraduate and post graduate teaching. Telephone poison information service was not available in either of centers. There was a limited capacity for qualitative and analytical toxicology. Common antidotes were available. There were limited surveillance activities to capture toxic risks existing in the community and also a deficiency was observed in chemical disaster planning. PCCs in Pakistan need capacity building for specialized training in toxicology, toxicovigilance, chemical disaster planning, analytical laboratory tests and telephone service for consultation in poisoning cases.

The Toxicology Investigators Consortium Case Registry—The 2012 Experience

In 2010, the American College of Medical Toxicology (ACMT) established its Case Registry, the Toxicology Investigators Consortium (ToxIC). All cases are entered prospectively and include only suspected and confirmed toxic exposures cared for at the bedside by board-certified or board-eligible medical toxicologists at its participating sites. The primary aims of establishing this Registry include the development of a realtime toxico-surveillance system in order to identify and describe current or evolving trends in poisoning and to develop a research tool in toxicology. ToxIC allows for extraction of data from medical records from multiple sites across a national and international network. All cases seen by medical toxicologists at participating institutions were entered into the database. Information characterizing patients entered in 2012 was tabulated and data from the previous years including 2010 and 2011 were included so that cumulative numbers and trends could be described as well. The current report includes data through December 31st, 2012. During 2012, 38 sites with 68 specific institutions contributed a total of 7,269 cases to the Registry. The total number of cases entered into the Registry at the end of 2012 was 17,681. Emergency departments remained the most common source of consultation in 2012, accounting for 61% of cases. The most common reason for consultation was for pharmaceutical overdose, which occurred in 52% of patients including intentional (41%) and unintentional (11%) exposures. The most common classes of agents were sedative-hypnotics (1,422 entries in 13% of cases) non-opioid analgesics (1,295 entries in 12% of cases), opioids (1,086 entries in 10% of cases) and antidepressants (1,039 entries in 10% of cases). N-acetylcysteine (NAC) was the most common antidote administered in 2012, as it was in previous years, followed by the opioid antagonist naloxone, sodium bicarbonate, physostigmine and flumazenil. Anti-crotalid Fab fragments were administered in 109 cases or 82% of cases in which a snake envenomation occurred. There were 57 deaths reported in the Registry in 2012. The most common associated agent alone or in combination was the non-opioid analgesic acetaminophen, being reported in 10 different cases. Other common agents and agent classes involved in death cases included ethanol, opioids, the anti-diabetic agent metformin, sedatives-hypnotics and cardiovascular agents, in particular amlodipine. There were significant trends identified during 2012. Abuse of over-the-counter medications such as dextromethorphan remains prevalent. Cases involving dextromethorphan continued to be reported at frequencies higher than other commonly abused drugs including many stimulants, phencyclidine, synthetic cannabinoids and designer amphetamines such as bath salts. And, while cases involving synthetic cannabinoids and psychoactive bath salts remained relatively constant from 2011 to 2012 several designer amphetamines and novel psychoactive substances were first reported in the Registry in 2012 including the NBOME compounds or "N-bomb" agents. LSD cases also spiked dramatically in 2012 with an 18-fold increase from 2011 although many of these cases are thought to be ultra-potent designer amphetamines misrepresented as "synthetic" LSD. The 2012 Registry included over 400 Adverse Drug Reactions (ADRs) involving 4% of all Registry cases with 106 agents causing at least 2 ADRs. Additional data including supportive cares, decontamination, and chelating agent use are also included in the 2012 annual report. The Registry remains a valuable toxico-surveillance and research tool. The ToxIC Registry is a unique tool for identifying and characterizing confirmed cases of significant or potential toxicity or complexity to require bedside care by a medical toxicologist.

In VitroandIn VivoEvaluation of Polyherbal Formulation against Russell’s Viper and Cobra Venom and Screening of Bioactive Components by Docking Studies

The present study emphasizes to reveal the antivenom activity of Aristolochia bracteolata Lam., Tylophora indica (Burm.f.) Merrill, and Leucas aspera S. which were evaluated against venoms of Daboia russelli russelli (Russell's viper) and Naja naja (Indian cobra). The aqueous extracts of leaves and roots of the above-mentioned plants and their polyherbal (1 : 1 : 1) formulation at a dose of 200 mg/kg showed protection against envenomed mice with LD50 doses of 0.44 mg/kg and 0.28 mg/kg against Russell's viper and cobra venom, respectively. In in vitro antioxidant activities sample extracts showed free radical scavenging effects in dose dependent manner. Computational drug design and docking studies were carried out to predict the neutralizing principles of type I phospholipase A2 (PLA2) from Indian common krait venom. This confirmed that aristolochic acid and leucasin can neutralize type I PLA2 enzyme. Results suggest that these plants could serve as a source of natural antioxidants and common antidote for snake bite. However, further studies are needed to identify the lead molecule responsible for antidote activity.

‘Do you know where your cyanide kit is?’: a study of perceived and actual antidote availability to emergency departments in the South West of England

ObjectiveThe authors set out to investigate perceived and actual availability of antidotes recommended for stocking in emergency departments (EDs) by the College of Emergency Medicine in EDs in the South...

Possible role of Mg2+ ion in the reaction of organophosphate (dichlorvos) with serine

▸Proposed mechanism for catalytic role of magnesium ion in nucleophic attack of serine to DDVP. ▸Magnesium reduces the pKa of serine hydroxyl group and favors the reaction of serine with DDVP. ▸It is proposed that magnesium acts through a ion radical mechanism. Abstract Organophosphate pesticides (OPs) inhibit both true and pseudo-cholinesterases by reaction with the hydroxyl group of serine in their active sites. Poisoning with OPs is commonly seen in clinics. A common antidote for OP poisoning is atropine but, after ageing and OP dealkylation, even oximes could not be effective. It has been shown that oximes are not always useful in management of OP poisoning. On the other hand, magnesium has been found effective in both clinical and experimental studies. Studies to find more effective antidotes for OP poisoning are in progress. Presently, the possible role of magnesium ion in catalysis of reaction of dichlorvos (2,2-dichlorovinyl dimethyl phosphate, DDVP), a water-soluble OP, with serine is proposed. The hydroxyl group of serine could be a target to which DDVP can react. Nucleophilic attack of pralidoxime to DDVP was previously investigated. To confirm the idea, data were derived from recent and previous research on the role of magnesium in phosphoryl group transfer reactions. Possible reactions of serine and pralidoxime with DDVP in the absence and the presence of magnesium ion were separately investigated theoretically. We propose that the chemical reaction of serine with DDVP exclusively occurs in the presence of a magnesium divalent cation, whereas the reaction of pralidoxime with DDVP occurs independent of the presence of the magnesium ion. The role of the dissociation constant (p K a ) of functional groups in these reactions seems important. It is suggested that application of serine in combination with the magnesium cation can become a more efficient antidote for treatment of OP poisoning.

The Toxicology Investigators Consortium Case Registry—The 2010 Experience

The American College of Medical Toxicology Case Registry was established in 2010 as a method of identifying cases cared for by medical toxicologists at participating institutions. The Registry allows for the extraction of information from medical records making it the most robust multicenter database on chemical toxicities in existence. The current report is a summary of the data collected in 2010. All cases seen by medical toxicologists at participating institutions were entered on a database. Information characterizing patients entered in 2010 was tabulated. Over the course of 2010, the number of institutions contributing cases grew from 4 to 50. Three thousand nine hundred forty-eight cases were entered. Emergency departments were the most common source of consultations, accounting for approximately 50% of the cases. The most common reason for consultations was for pharmaceutical overdoses, which occurred in 42% of the patients. The most common classes of agents were non-opioid analgesics (14%), sedative/hypnotics/muscle relaxants (10%), ethanol (8%), and opioids (8%). N-acetylcysteine was the most common antidote used, followed by opioid antagonists, sodium bicarbonate, and physostigmine. Anti-crotalidae Fab fragments were administered in 72% of the cases in which an antivenin was used. Signals were detected suggesting the possibility that amlodipine and metoprolol were associated with greater toxicity than had been previously recognized. The Registry can identify and characterize patients who have sufficient toxicity to require a consultation by a medical toxicologist. Hypotheses for further investigation emerged from the data. The Registry appears to be a potentially powerful tool for toxicovigilance and research.

Diagnosis and Management of the Poisoned Child

Pediatric toxic ingestions are treated commonly by pediatricians and emergency physicians. Significant injury after these ingestions is infrequent, but identifying the dangerous ingestion is sometimes a difficult task. By performing a detailed history, focused physical examination, and directed laboratory evaluation, an estimation of risk can be developed. This article introduced the term "toxic triage" to describe this process. The toxic triage estimation allows the clinician to make thoughtful decontamination and treatment decisions. Familiarity with the literature supporting or refuting each decontamination method allows educated decisions to be made. Supportive care is an integral part of treatment for all poisonings, from asymptomatic to life-threatening. Most antidotes are used rarely in clinical practice, but familiarity with common antidotes benefits those patients with specific hazardous ingestions. Prevention efforts have the potential to decrease the incidence of pediatric poisonings. The universal poison control center number provided should be distributed and posted in homes, clinics, and emergency departments.

Nerve Agent Destruction by Recyclable Catalytic Magnetic Nanoparticles

Organophosphorus pesticides and warfare agents are not readily hydrolyzed in aqueous media without applying extremes of pH, heat, or bleach. We show that suspensions of magnetite (Fe3O4) nanoparticles modified with a common antidote, 2-pralidoxime (PAM) or its polymeric analogue, poly(4-vinylpyridine-N-phenacyloxime-co-acrylic acid), catalyze the hydrolysis of an organophosphate (OP) compound serving as a model of the warfare nerve agents, at neutral pH. The oxime-modified magnetite particle serves as a nanosized particulate carrier with a powerful α-nucleophile, the oximate group, immobilized on its surface. The rates of OP hydrolysis by the PAM-modified magnetite are comparable to those of the most potent copper-based catalysts. The oxime-modified magnetite nanoparticles are colloidally stable at neutral pH and are readily recovered for reuse from the aqueous milieu by high-gradient magnetic separation methods with no loss of catalytic activity.

On-site availability of selected antidotes: Results of a survey of Massachusetts hospitals

Hospital pharmacies in Massachusetts were surveyed to determine their patterns of stocking antidotes. Mailed questionnaires were completed by hospital pharmacy directors at 82 of 93 acute care institutions (87% response rate). Results confirmed great variability in on-site accessibility of antidotes. Only 8 of the 82 hospitals (9.8%) stocked all of 14 common antidotes inventoried by the survey. Even fewer hospital pharmacies stocked specific antidotes (eg, Crotalid anti-venin, digoxin-specific Fab antibodies, pyridoxine) in an adequate quantity to treat one poisoned adult. Larger hospitals and those with a 24-hour pharmacy were more likely to have certain antidotes than smaller institutions. We conclude that Massachusetts hospitals do not carry complete inventories of 14 common antidotes. It is important that poisoned patients be referred to medical centers with adequate toxicological care. Improved guidelines for the accessibility of antidotes need to be developed and made available to hospital pharmacies and emergency departments.

1978. Ametryne disposal by the rat: Oliver, W. H., Born, G. S. & Ziemer, P. L. (1969). Retention, distribution, and excretion of ametryne (2-methylmercapto-4-ethylamino-6-isopropylamino- s-triazine) in the rat. J. agric. Fd Chem.17, 1207

Organophosphate pesticides (OPs) inhibit both true and pseudo-cholinesterases by reaction with the hydroxyl group of serine in their active sites. Poisoning with OPs is commonly seen in clinics. A common antidote for OP poisoning is atropine but, after ageing and OP dealkylation, even oximes could not be effective. It has been shown that oximes are not always useful in management of OP poisoning. On the other hand, magnesium has been found effective in both clinical and experimental studies. Studies to find more effective antidotes for OP poisoning are in progress. Presently, the possible role of magnesium ion in catalysis of reaction of dichlorvos (2,2-dichlorovinyl dimethyl phosphate, DDVP), a water-soluble OP, with serine is proposed. The hydroxyl group of serine could be a target to which DDVP can react. Nucleophilic attack of pralidoxime to DDVP was previously investigated. To confirm the idea, data were derived from recent and previous research on the role of magnesium in phosphoryl group transfer reactions. Possible reactions of serine and pralidoxime with DDVP in the absence and the presence of magnesium ion were separately investigated theoretically.We propose that the chemical reaction of serine with DDVP exclusively occurs in the presence of a magnesium divalent cation, whereas the reaction of pralidoxime with DDVP occurs independent of the presence of the magnesium ion. The role of the dissociation constant (pKa) of functional groups in these reactions seems important.It is suggested that application of serine in combination with the magnesium cation can become a more efficient antidote for treatment of OP poisoning.