Enfrentamiento inicial de las intoxicaciones por medicamentos orales en el servicio de urgencia / Initial management of toxic exposures to oral drugs in the emergency department

Las intoxicaciones en Chile siguen siendo un motivo importante de consulta en el servicio de urgencia (SU). Tanto intoxicaciones accidentales como intencionales constituyen una fuente de morbimortalidad y gasto de recursos monetarios no solo en Chile, si no que en todo el mundo. Debido a los múltiples compuestos que pueden producir una intoxicación grave, sigue siendo un desafío para el equipo de salud su enfrentamiento y manejo oportuno. Los médicos que tratan a estos pacientes deben ser sistemáticos y ordenados en su enfrentamiento, ya que la presentación clínica es variada y depende del agente ingerido, co-ingestas, si es aguda o crónica o concomitante con otras patologías (trauma, infecciones, etc.). El manejo está dirigido a las maniobras básicas de reanimación y soporte vital, prevención de absorción del tóxico y cuando corresponda, la administración del antídoto. La evaluación y tratamiento inicial serán abordados en esta revisión, temas específicos para diferentes drogas serán discutidos de forma separada. Objetivo: entregar las nociones básicas del enfrentamiento y manejo terapéutico inicial de un paciente intoxicado desde la perspectiva de la medicina de urgencias. Método: se realizó una revisión bibliográfica de la literatura científica, presentándose la evidencia actual del manejo e intervenciones terapéuticas utilizadas actualmente de un paciente intoxicado.

In Chile, poisonings are a frequent reason for emergency department visits. Accidental and intentional poisonings constitute an important source of worldwide morbidity, mortality and health care costs. Because of the heterogeneous presentations of poisonings, and the unknown exposure, it is always challenging for healthcare providers. Doctors who treat these patients must remember to be systematic and structured in their evaluation since the clinical presentation is not only determined by the exposure itself but also by co-ingestions, the time of presentation, whether the exposure is acute or chronic, and other concomitant health issues (trauma, hypothermia, comorbidities). The management focuses on basic resuscitation and life support, prevention of absorption of the toxin, and when appropriate, administering an antidote. Initial evaluation and treatment will be addressed in this review, and specific issues for different drugs will be discussed elsewhere. Objective: to describe the basic concepts to assess and manage the initial encounter of a poisoned patient from the perspective of emergency medicine. Methods: a bibliographic review of the scientific literature was carried out, presenting the current evidence of the management and therapeutic interventions currently used in an intoxicated patient.

Escorpionismo en la población amazónica del cantón Taisha en Ecuador / Scorpion stings in the Amazonian population from Taisha Canton in Ecuador

Introducción: En el Ecuador se desconoce la frecuencia, los factores de riesgo, el efecto preciso de las picaduras de escorpión, sus toxinas, la fisiopatología e interacción con la población. Objetivo: Registrar la incidencia de las picaduras de escorpión, el cuadro clínico, su manejo y las limitaciones para la obtención del antídoto en Ecuador. Métodos: Se realizó un estudio de cohorte retrospectivo, en el cual se recolectaron datos como edad, sexo, residencia, sitio corporal de picadura, cuadro clínico, tratamiento, estancia médica, referencia a unidad de mayor complejidad, morbilidad y mortalidad, durante el periodo entre enero de 2016 y noviembre de 2018 en la población amazónica del cantón Taisha, provincia de Morona Santiago, Ecuador. Resultados: Se evaluaron 134 picaduras de escorpión, las cuales predominaron en personas adultas (70,9 %). La región corporal más frecuente de picadura fue en las extremidades superiores e inferiores (92,5 %) y el nivel de intoxicación grave correspondió al 12,7 %. La estacionalidad de las picaduras de escorpión predominó en los meses de octubre, abril, diciembre y marzo. La presentación de la morbilidad anual fue mayor en el año 2017 (52,9 %). Conclusiones: Existe una alta incidencia de picaduras de escorpión en la zona de estudio. En el Ecuador la accesibilidad al antídoto es limitada, por lo que es necesario realizar más investigaciones en el tema, incluyendo intervenciones preventivas y curativas.

Introduction: In Ecuador, the frequency, risk factors, precise effects, toxins, pathophysiology and interaction with the population of scorpion stings are unknown. Objective: To report on the incidence of scorpion stings, its clinical picture and management, and the limitations for obtaining an antidote in Ecuador. Methods: A retrospective cohort study was conducted and data was collected on the age, gender, place of residence, site of sting, clinical picture, treatment, hospital stay, referral to higher complexity unit, morbidity, and mortality from January 2016 to November 2018 in the Amazonian population from Taisha canton, Morona-Santiago province in Ecuador. Results: 134 scorpion stings were evaluated. Most cases were adults (70.9%). The most frequent region stung by scorpions were the upper and lower extremities (92.5%) and severe intoxication level accounted for 12.7% of cases. The highest incidence of scorpion stings occurred in October, April, December and March. Annual morbidity was higher in 2017 (52.9%). Conclusions: There is a high incidence of scorpion Sting in the area under study. Accessibility to an antidote is limited in Ecuador; therefore, further research on this topic and on preventive and curative interventions are necessary.

Research progress of potential anti-tumor and anti-inflammatory target PARP14 / 中国药理学通报

PARP14 is an intracellular single AI)P-ribose transferase member of the superfamily of polyADP-ribose polymerases.PARP14 is associated with a wide range of biochemical transfor-mations in vivo through poly( ADP-ribosylation, PAKs) modifi- cation of target proteins.For example, it plays an important part in eellular transcriptional regulation, stress response, DNA re-pair, RNA splieing, mitoehondrial function, division, and nu- cleosome formation.PAR PI 4 is elosely related to the development and progression of cancers (such as hepatoeellular carcino- ma, multiple myeloma and pancreatic cancer) , metabolie diseases, and inflammatory diseases, making it a potential dnig dis- eovery target.This research reviews the structure and biological functions of PARP14, and summarizes the role of PARP14 in disease, as well as the existing PARP14 small molecule inhibitors and decompressors.It provides a brief update to the research and development of PARP14 inhibitors and decompressors to assist in the development of selective PARP14 inhibitors and decompressors.It provides reference for the research and development of drugs or chemical sensitizers targeting PARP14.

Progress in lipid emulsions as antidotes to reverse drug poisoning / 中国药科大学学报

@#Due to their good safety, wide application scope and quick onset time, lipid emulsions are full of promise to reverse drug poisoning. In this review, a number of clinical case reports were summarized to analyze the detoxification effect of lipid emulsions on local anesthetic, antiarrhythmic, psychotropic and organophosphate poisoning, as well as the possible adverse reactions of lipid emulsions therapy.Meanwhile, the mechanisms underlying lipid emulsions therapy, such as lipid sink theory, enhanced body basal metabolism and positively affected cardiovascular function, were fully interpreted.Besides, a few potential solutions to the problems still existing in lipid emulsions therapy were proposed, in order to consolidate the understanding of lipid emulsions therapy and promote its rational application in reversing drug poisoning.

Manejo agudo de la intoxicación medicamentosa / Acute management of drug intoxication

Resumen Las intoxicaciones o las sobredosis de drogas constituyen una fuente importante de morbilidad, mortalidad y gasto en salud en todo el mundo. Especialmente en adultos menores de 35 años, las intoxicaciones vienen a ser la principal causa de paro cardíaco no traumático, siendofármacos más comunes involucrados, analgésicos, antidepresivos, opioides, sin embargo, esto puede variar. Es importante realizar un abordaje rápido, con base en interrogatorio, información de cualquier testigo y evidencia, además la clínica del paciente. El paro cardíaco debido a toxicidad se maneja de acuerdo conlos estándares actuales de reanimación cardiopulmonar básica y avanzada, siguiendo los principios del A, B, C, D, E. Las manifestaciones clínicas y abordaje clínico pueden variar bastante dependiendo de la sustancia involucrada. Las pruebas de laboratorio casi nunca están disponibles en un marco de tiempo que respalde las decisiones de reanimación tempranas, aún así, es recomendable realizarlas. En general los efectos tóxicos pueden reducirse si se limita la absorción del o los fármacos o se aumenta su eliminación. Además, se puede bloquear efectos farmacológicos no deseados con los llamados antídotos. El uso del carbón activado, algunos antídotos específicos, y tratamientos extracorpóreos también se contemplan en la presente revisión.

Abstract Poisoning or drug overdose is a major source of morbidity, mortality and health expenditure worldwide, especially in adults under 35, where it is the leading cause of non-traumatic cardiac arrest, being more common drugs involved, analgesics, antidepressants, opioids, however, this may vary. It is important to make a quick approach, based on questioning, information from any witness and evidence, and the patient's clinic. Cardiac arrest due to toxicity is managed according to current Basic and Advanced life support standards, following the principles of A, B, C, D, E. Clinical manifestations and clinical approach can vary considerably depending on the substance involved. Laboratory tests are almost never available in a time frame that supports early resuscitation decisions, yet it is advisable to perform them. In general, the toxic effects can be reduced if the absorption of the drugs is limited or their elimination increased. In addition, you can block unwanted pharmacological effects with so-called antidotes. The use of activated charcoal, specific antidotes, and extracorporeal treatments are also covered in this review.

Novel small molecule retrograde transport blocker confers post-exposure protection against ricin intoxication

Ricin is a highly toxic type 2 ribosome-inactivating protein (RIP) which is extracted from the seeds of castor beans. Ricin is considered a potential bioterror agent and no effective antidote for ricin exists so far. In this study, by structural modification of a retrograde transport blocker Retro-2, a series of novel compounds were obtained. The primary screen revealed that compound has an improved anti-ricin activity compare to positive control. pre-exposure evaluation in Madin-Darby Canine Kidney (MDCK) cells demonstrated that is a powerful anti-ricin compound with an EC of 41.05 nmol/L against one LC (lethal concentration, 5.56 ng/mL) of ricin. Further studies surprisingly indicated that confers post-exposure activity against ricin intoxication. An study showed that 1 h post-exposure administration of can improve the survival rate as well as delay the death of ricin-intoxicated mice. A drug combination of with monoclonal antibody mAb4C13 rescued mice from one LD (lethal dose) ricin challenge and the survival rate of tested animals is 100%. These results represent, for the first time, indication that small molecule retrograde transport blocker confers both and post-exposure protection against ricin and therefore provides a promising candidate for the development of anti-ricin medicines.

National Antidote of Poisoning Distribution System: New Initiatives in Saudi Arabia

Objective: To declare the national antidote of poisoning distribution system as new initiatives in the Kingdom of Saudi Arabia. Methods: It is a new initiative project, the national antidote of poisoning distribution system. The project drove the antidote of poisoning distribution guidelines and the international business model, pharmacy project guidelines project management institution guidelines of a new project. The initiative project is written through project management professionals and consisted of several parts, including the initial phase, the planning phase, the execution phase and the monitoring and controlling phase. Results: The antidote of poisoning distribution system with a defined vision, mission and goals was initiated. The services had various advantages with clinical and economic impacts on patients and healthcare services as illustrated in the review. The extension of the project was assured by risk management elements description. Furthermore, the monitoring and controlling of the services was demonstrated. The conversion to operation project though closing project stage was revealed in the analysis. Conclusion: The national antidote of poisoning distribution system is new initiative project and is considered as a part of the management of poisoning. There are multiple locations of antidote distribution services suggested and it is highly required in the Kingdom of Saudi Arabia.

Observational Study On Poison Cases In A Tertiary Care Hospital

Objective: To evaluate the prevalence, pattern, and cause of poisoning. To characterize the poisoning cases admitted in a tertiary care hospital; followed by the outcome and to observe the antidote given for the poison cases. Methods: This observational study was undertaken in emergency departments (EMD) and Medical Record Department (MRD). Totally 557 poison cases was recruited in this study. Grade of poison was assessed by using poison severity score. Statistical analysis was done by using Statistical Package for Social Sciences (SPSS). Results: A total of 557 poison cases were identified in 2, 39, 828 patients out of which 360(64%) were suicidal and 189(34) cases admitted were accidental. The patients who were admitted between 2-5 h after exposed to poison were found to be more followed by 0-1 hr,>1-2 h,>6-24 h,>24 h and>5-6 h. More number of cases were seen in the others (Synthetic cow dung powder and medicine) type of poison 296(53%) followed by household poisoning 93(17%), bites 86 (15%), insecticide poisoning 64(12%) and food poisoning 16(3%). Activated charcoal was the maximum used antidote. Conclusion: Through this study, it was found that suicidal poisoning was the most common type.

Intoxicación por organofosforados / Organophospate poisoning

Resumen La intoxicación por organofosforados es de gran importancia en el campo de la medicina, debido a su uso frecuente en la actividad agrícola, las intoxicaciones producidas por estos agentes pueden ser ocupacionales, accidentales, y con mayor frecuencia por ingesta voluntaria. Una de las mayores repercusiones de los organofosforados es la inhibición del acetil colinesterasa, enzima encargada de hidrolizar el acetil colina. Las manifestaciones clínicas de la intoxicación aguda se deben a la estimulación de receptores muscarínicos y nicotínicos, entre ellas broncorrea, salivación, lagrimeo, broncoespasmo, defecación, emesis, miosis, entre otros. El diagnóstico se realiza mediante la historia clínica y examen físico, de manera adicional con la detección de los niveles en sangre eritrocitaria de acetil colinesterasa o de los metabolitos de los organofosforados. El manejo incluye la descontaminación del agente, la revisión del estado respiratorio y el acceso al soporte ventilatorio, posteriormente se procede con el tratamiento farmacológico que incluye el uso de la atropina, pralidoxima y diazepam. El presente artículo constituye una revisión bibliográfica sobre la intoxicación por organofosforados, sus manifestaciones clínicas, diagnóstico y tratamiento.

Abstract Organophosphorus poisoning is of great importance in the field of medicine due to its frequent use in agriculture, the poisoning by exposure to these agents can be occupational, accidental, and frequently due to voluntary intake. Organophosphorus' intake most notable effects are produced by the inhibition of the acetyl cholinesterase, responsible for hydrolyzing acetyl choline. Clinical manifestations of acute intoxication typically include bronchorrhea, salivation, lacrimation, bronchospasm, defecation, emesis, miosis, among others and they occur due to the stimulation of muscarinic and nicotinic receptors. Diagnosis is made through the interrogation and physical examination, in addition to the detection of acetyl cholinesterase levels or the organophosphates' metabolites in blood testing. Management includes decontamination of the agent, review of respiratory status and access to ventilatory support, followed by pharmacological treatment that includes the use of atropine, pralidoxime and diazepam. The present article constitutes a bibliographic review about the organopho sphorus intoxication, its clinical manifestations, diagnosis and treatment.

A prospective observational study and survival pattern of organo phosphorous poisoning patients with intensive care treatment in a tertiary care hospital

Background: Organophosphate poisoning is poisoning due to organophosphates (OP’s), used in insecticides, medications and nerve agents. It occurs mostly during suicide attempts in the farming areas, developing world and less by accident. The study is to evaluate the drugs used, respiratory conditions, complications occurred during course of treatment.Methods: This was a prospective observational study conducted for 9 months in a tertiary care hospital. The study was conducted in a 500 bedded tertiary care hospital in an intensive care unit. The study was conducted for nine months (September 2016 - May 2017).Results: A total of 234 patients who had consumed OPP with known and unknown agents were admitted in the emergency department. Out of which 180 males and 54 females.Conclusions: This study concluded that the patients consumed poison is mainly due to mental disturbances and financial problems. The stress and burden on the life will shows the effect after consumption, the maximum people suffer with respiratory problems due to poison consumption. If the government should take the measures to avoid consumption of poison and availability of poison to the public may overcome the complications and reduce the deaths due to poison.

Clinical study of the therapeutic efficacy from different dosages of pralidoxime chloride used in patients with acute organophosphorus pesticide poisoning / 中华急诊医学杂志

Objective To investigate the effect of different doses of pralidoxime chloride on clinical outcome including recovery rate and mortality in patients with acute organophosphorus pesticide poisoning.Methods According to the total amount of pralidoxime chloride administered over the first 24 hours or entire duration of hospitalization,a cohort of 163 organophosphorus pesticide poisoning patients,admitted from February 2004 to December 2014 were assigned to different groups followed by a retrospective analysis.Comparisons of recovery rate,mortality rate,mean length of hospital stay,and duration of mechanical ventilation were made among groups.SPSS 18.0 was used to analyze categorical variables between the data of groups with x2 test/Fisher exact probability method and numerical variables with t test or One-way ANOVA,and statistical significance was set as P ＜ 0.05.Results According to the amount of pralidoxime chloride given over the first 24 hours,the recovery rate and the mortality rate were significantly improved in the experimental group (pralidoxime chloride ＞ 2 g) than in the control group (pralidoxime chloride ＜ 2 g) (P =0.04).There was no significant difference in mean length of hospital stay between the experimental group and the control group (P =0.171),and there were statistically significant differences in recovery rate and mortality rate among the four dose-response subgroups (total dosage administered in 24 hours in group A ＜ 1 g,in group B ＜2 g,in group C ＜4 g and in group D ＞4 g) (P =0.034).Based on the total amount of pralidoxime chloride prescribed in the entire duration of hospital stay,the recovery rate and mortality rate were significantly better in the experimental group than those in control group (P =0.002),and among the three dose-response subgroups,the significant difference in recovery rate and mortality rate were also observed (P =0.006).Conclusions Increased amounts of pralidoxime chloride prescribed in the first 24 hours and in the whole hospitalized period can improve the recovery rate and reduce the mortality rate in organophosphorus pesticide poisoning patients.

Antidotal effects of curcumin against neurotoxic agents: An updated review

Curcumin (CUR), the main phenolic composition in turmeric, shows preventive effects in various diseases. CUR is commonly found in the Curcuma species and historically applied in herbal medicine. Numerous studies have indicated that CUR possesses protective effects against toxic agents in the various animal tissues including the brain. This study found that CUR may be effective in nervous system problems induced by neurotoxic agents. However, due to the lack of information on human, more investigations are needed to determine the efficacy of CUR as an antidote matter. The current study aimed to critically review the recent literature data from 2014 to 2016 that regarding the therapeutic aspects of CUR versus neurotoxic agents-induced brain damage and its involved mechanisms.

Antidotal effects of curcumin against neurotoxic agents: An updated review

Curcumin (CUR), the main phenolic composition in turmeric, shows preventive effects in various diseases. CUR is commonly found in the Curcuma species and historically applied in herbal medicine. Numerous studies have indicated that CUR possesses protective effects against toxic agents in the various animal tissues including the brain. This study found that CUR may be effective in nervous system problems induced by neurotoxic agents. However, due to the lack of information on human, more investigations are needed to determine the efficacy of CUR as an antidote matter. The current study aimed to critically review the recent literature data from 2014 to 2016 that regarding the therapeutic aspects of CUR versus neurotoxic agents-induced brain damage and its involved mechanisms.

Study on Current Changes of Atropine Regimen in Organophosphate Pesticides Poisoning / 계명의대학술지

Appropriate early atropinization is important for the recovery and prognosis of the organophosphate pesticides poisoning patient. However, recommended guidelines of atropine regimen in the treatment of organophosphate pesticides poisoning is not present in Korea. The authors analyzed the domestic literatures and books to investigate a trend of the regimen of atropine for organophosphate pesticides poisoning. We found 11 papers and 6 books about organophosphate pesticides poisoning that published in Korea. Then calculates elapsed time for atropinization by the each regimen of atropine. References recommendations varied markedly - atropinization of an average patient, requiring the mean dose of 23.4 mg, would have taken 15 to 432 minutes; atropinization of a very ill patient, requiring maximum dose of 75 mg, would have taken 20 to 1,385 min, Recently, it suggested atropine regimen that doubling the dose for organophosphate pesticides poisoning in Korea. So it needs to study for ensure a higher validity and application of organophosphate pesticides poisoning patients.

Antidote for organophosphate insecticide poisoning: atropine and pralidoxime

Acute organophosphate (OP) poisoning produces cholinergic symptoms resulting from the inhibition of cholinesterase, and the overstimulation of muscarinic and nicotinic receptors in the synapses. The dominant clinical features of acute cholinergic toxicity include bradycardia, miosis, lacrimation, salivation, bronchorrhea, and bronchospasm. All symptomatic patients should receive therapy with oxygen, atropine, and pralidoxime. Atropine works as a physiologic antidote by competitively occupying muscarinic receptor sites, reducing the effects of excessive acetylcholine. Atropine should be immediately administered, and the dose can be titrated according to the severity of OP poisoning. A large dose may be necessary to overcome the excessive cholinergic state in case of severe poisoning. Pralidoxime is a biochemical antidote that reactivates acetylcholinesterase by removing OP from it. It is effective in treating both muscarinic and nicotinic symptoms. After some period of time, the acetylcholinesterase-OP compound undergoes a conformational change, known as aging, which renders the enzyme irreversibly resistant to reactivation by a pralidoxime. There has been a great deal of controversy over the effectiveness of pralidoxime in acute OP poisoning. However, it may be beneficial to administer pralidoxime for a sufficient period in case of severe poisoning with a large quantity of OP, which is common in Korea.

Antidotes of cyanide intoxication

Cyanide poisoning can occur from industrial disasters, smoke inhalation from fire, food, and multiple other sources. Cyanide inhibits mitochondrial oxidative phosphorylation by blocking mitochondrial cytochrome oxidase, which in turn results in anaerobic metabolism and depletion of adenosine triphosphate in cells. Rapid administration of antidote is crucial for life saving in severe cyanide poisoning. Multiple antidotes are available for cyanide poisoning. The action mechanism of cyanide antidotes include formation of methemoglobin, production of less or no toxic complex, and sulfane sulfur supplementation. At present, the available antidotes are amyl nitrite, sodium nitrite, sodium thiosulfate, hydroxocobalamin, 4-dimethylaminophenol, and dicobalt edetate. Amyl nitrite, sodium nitrite, and 4-dimethylaminophenol induce the formation of methemoglobin. Sodium thiosulfate supplies the sulfane sulfur molecule to rhodanese, allowing formation of thiocyanate and regeneration of native enzymes. Hydroxocobalamin binds cyanide rapidly and irreversibly to form cyanocobalamin. Dicobalt edetate acts as a chelator of cyanide, forming a stable complex. Based on the best evidence available, a treatment regimen of 100% oxygen and hydroxocobalamin, with or without sodium thiosulfate, is recommended for cyanide poisoning. Amyl nitrite and sodium nitrite, which induce methemoglobin, should be avoided in victims of smoke inhalation because of serious adverse effects.

Traditional Use of Plants against Snakebite in Sugali tribes of Yerramalais of Kurnool district, Andhra Pradesh, India

Objective: To conduct ethnobotanical survey in Yerramalais forest among Sugali tribes and collect information on medicinal plants to used to in the treatment of snake bite. Snakebite has been a major cause of mortality of tribals and their livestock. Methods: The study was conducted during 2009-2011 visiting regularly Sugali Thandas and Lobais. Following the method of Jain and Goel. First hand information on their traditional medicine was recorded, repeated enquiries were made to understand their knowledge, methods of diagnosis and treatment. Data were collected on the specific part of the plants used collection, method of usage of the drug and dosage of the drug ,dosage of administration. Results: The paper provides information about Ehanobatanical and Scientific evidences of 23 medicinal plants which are used by sugalis as antidote for snake bite. Conclusion: Traditional medicine remains an integral part of the health system in this area Antidote medicinal plants play an important role in health and livelihood of Sugali Tribal people.

Cyanide-induced changes in the levels of neurotransmitters in discrete brain regions of rats and their response to oral treatment with a-ketoglutarate.

Cyanide is a potential suicidal, homicidal and chemical warfare agent. It produces histotoxic hypoxia following inhibition of cytochrome c oxidase, a terminal respiratory chain enzyme. The profound metabolic changes lead to neurotoxicity including alterations in the levels of neurotransmitters. The present study addressed the effect of acute exposure of lethal and sub-lethal doses of potassium cyanide (KCN; 0.75 or 2.0 LD50; po) on the levels of neurotransmitters in discrete brain regions of rats and its response to treatment with a-ketoglutarate (-KG; 0.5 g/kg; po; -10 min) alone or with sodium thiosulphate (STS; 1.0 g/kg; ip; -15 min). KCN significantly decreased norepinephrine, dopamine and 5-hydroxytryptamine levels in different brain regions which were resolved by a-KG and/or STS. Corpus striatum and hippocampus were more sensitive as compared to cerebral cortex and hypothalamus. -KG, a potential cyanide antidote alone or with STS showed neuroprotective effects against cyanide.

Pharmacological agents in the prophylaxis/treatment of organophosphorous pesticide intoxication.

Organophosphorus pesticide poisoning causes tens of thousands of deaths each year across the world. Poisoning includes acute cholinergic crisis as a result of AChE inhibition, intermediate syndrome (IMS) due to neuromuscular necrosis and organophosphate-induced delayed neuropathy (OPIDN) due to inhibition of neuropathy target esterase (NTE). Standard treatment for acute poisoning involves administration of intravenous atropine, oxime 2-PAM to counter AChE inhibition and diazepam for CNS protection. However clinical trials showed ineffectiveness of the standard therapy regimen. Although new oximes that can reactivate both peripheral and cerebral AChE and other prophylactic agents such as human serum butyrylcholinesterase (Hu BChE), sodium bicarbonate, huperzine A (a reversible ChE inhibitor) with imidazenil (a GABAA receptor modulator) have been proved effective in animal models, systematic clinical trials in patients are warranted. For IMS which is non-responsive to standard therapy, supportive therapy specifically artificial respiration followed by recovery is indicated. For OPIDN which has a different target (NTE) than AChE, standard therapy is ineffective. However neuroprotective drugs such as corticosteroids proved partially effective. Pretreatment with protease inhibitor PMSF has been shown to protect the aging of NTE and prevent the development of delayed symptoms in hens. Since the biology of NTE is being explored, new pharmacological agents should be developed in future. OP pesticide poisoning is a serious condition that needs rapid diagnosis and treatment. Since respiratory failure is the major reason for mortality, artificial respiration, careful monitoring, appropriate treatment and early recognition of OP pesticide poisoning may decrease the mortality rate among these patients.

Methylene Blue

Methylene blue is a very effective reducer of drug-induced methemoglobinemia. It has dose-dependent oxidation or reduction properties. In most cases, a dose of 1 to 2 mg/kg IV given over 5 minutes and immediately followed by a 15- to 30-mL fluid flush to minimize the local pain is both effective and relatively safe. The onset of action is quite rapid, and the effects are usually seen within 30 minutes. The dose may be repeated after 30 to 60 minutes and then every 2 to 4 hours as needed. The total dose should not exceed 7 mg/kg as a single dose or 15 mg/kg within 24 hours. Repeated treatment may be needed for treating compounds that have prolonged elimination or those compounds that undergo enterohepatic recirculation (e.g., dapsone). Methylene blue can cause dose-related toxicity. At high doses, methylene blue can also induce an acute hemolytic anemia and rebound methemoglobinemia. The reasons for treatment failure with methylene blue include ineffective GI decontamination, the existence of other forms of hemoglobin (e.g., sulfhemoglobin), a low or high dose of methylene blue and the toxicokinetics of some agents, such as aniline, benzocaine or dapsone.