Suicidal Poisoning Research Articles

Efficacy and safety of pulse immunosuppressive therapy with glucocorticoid and cyclophosphamide in patients with paraquat poisoning: A meta-analysis

Paraquat (PQ) is widely used in developing countries. Accidental or suicidal PQ poisoning is a public health concern due to lack of effective treatment. Because the role of pulse immunosuppressive therapy with glucocorticoid and cyclophosphamide for PQ poisoning is uncertain, we performed a meta-analysis to investigate the efficacy and safety of the therapy. A systematic literature search for randomized controlled trials (RCTs) and other clinical studies was performed in Pub Med, Embase, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature and Retrieval System, and Chinese Medical Current Contents. We estimated pooled relative risk ratios (RRs) and 95% confidence intervals (CIs) using a fixed effect model or random effect model. Outcomes included mortality, incidence of acute renal failure (ARF) and hypoxia, and leucopenia. Five studies (three RCTs) involving 332 PQ poisoning patients met the criteria. The mortality of moderate to fulminant poisoning patients receiving the pulse therapy was lower than that of the controls (60.4% vs. 85.3%; RR 0.71, 95% CI: 0.59, 0.86, P=0.0004). The therapy also reduced the mortality of patients with moderate to severe PQ poisoning (45.1% vs. 79.1%, RR 0.45; 95% CI: 0.28, 0.75, P=0.002). However, the therapy did not decrease the incidence of ARF and hypoxia. In addition, the pulse therapy caused more leucopenia than the controls (36.9% vs. 2.6%; RR: 9.12; 95% CI: 3.65, 22.81, P<0.00001). Pulse immunosuppressive therapy with glucocorticoid and cyclophosphamide may reduce the mortality of PQ poisoning patients, although the therapy may cause leucopenia.

Development and Structural Modifications of Cholinesterase Reactivators against Chemical Warfare Agents in Last Decade: A Review.

Organophosphate (OP) pesticides and nerve agents are responsible for suicidal and accidental poisonings. The acute toxicity of nerve agents leads to progressive inhibition of the enzyme acetylcholinesterase (AChE) by phosphylation of serine residue at the active site of gorge. The recent massive destruction of Syrian civilians by nerve gas sarin, has again renewed the research attention of global science fraternity towards nerve agents, their mode of action and most prominently their therapeutic treatment. This review is principally focused on nerve agent intoxication. The common approach to deal with OP-intoxication is, application of antimuscarinic drug (atropine), anticonvulsant drug (diazepam) and clinically used oximes (pralidoxime, trimedoxime, obidoxime and asoxime). However, the existing therapeutic approach is arguable and has several failings to cure all kinds of nerve agent poisonings. Considering this issue, numerous oximes have been synthesized and screened through various in-vitro and in-vivo studies in last decade to overcome the downsides. At present, only a few oximes (bis pyridinum-oximes) exhibit sound efficacy against selective OPs. In spite of extensive efforts, till date no oxime is available as a universal antidote against all the classes of OPs. This review is centered on the recent developments and structural modification of AChE reactivators against nerve agent toxicity. In particular, a deeper look has been taken into chemical modifications of the reactivators by incorporation of different structural moieties targeted towards the increased reactivation affinity and improved blood brain barrier (BBB) penetration.

Ventricular bigeminy in acute organophorous poisoning – A rare ECG finding

India being a land of farmer, the pesticides are freely and easily available and therefore organophosphorous poisoning is one of the major health issues. Suicidal poisoning is more common than accidental poisoning. Cardiac manifestations of organophosphorous poisoning are well known. It results in various electrocardiographic changes from sinus tachycardia to ST elevation. We hereby present a rare ECG finding of ventricular bigeminy in a case of acute organophosphorous poisoning.

Organophosphorus poisoning: A social calamity

Poisoning with organophosphorus (OP) compounds is a global public health problem. According to World Health Organization (WHO), 3 million cases of pesticide (mainly OP compounds) poisoning occur every year, resulting in an excess of 250,000 deaths. Of these, about 1 million are accidental, and 2 million are suicidal poisonings. The incidence has steadily increased in the recent past and has reached a level in the developing countries, where it can be called a social calamity. Diagnosis is mainly on clinical grounds. The wellknown antidotes of OP poisonings are atropine and oximes. However, investigations over the recent years have introduced new adjunct therapy and cheap medications such as sodium bicarbonate and magnesium sulfate as well as antioxidants that should be considered for the management of OP poisoning. While efficacy of atropine is clinically proven, clinical experience with pralidoxime has been controversial. A lot of new modalities of management like K-oximes, hemoperfusion, and Fresh frozen plasma are under evaluation. Prevention still appears to be the best modality of management. Appropriate legislations and pesticides control are recommended for the developing countries to prevent occupational, accidental, and intentional poisonings.

The Study of CNS Manifestations in Aluminium Phosphide Poisoning

With rapid development in the field of science & technology and green revolution in the agricultural sector, the problem of acute aluminium phosphide poisoning leading to morbidity and mortality is spreading like a wild fire. Different disciplines of medical science are working on various aspects both from treatment as well as preventive point of view. Aluminium Phosphide is a very toxic, cheap, ideal suicidal and lethal protoplasmic poison involving all generations and organ systems of the body. Although its incidence was unknown before 1980 but now it has surpassed every other poisoning in India especially in the northern states and has created havoc with the human lives. Our study showed that males (1.94:1) are the major sufferer with high mortality rate (76%). The freshness of tablet and lack of specific antidote are directly related to its poor prognosis. Major CNS manifestations are dizziness (52%) and headache (44%). Loss of consciousness is only the terminal event and sufficient time is available to record the dying declaration. Magnesium sulphate has some role in its management.

Rapid method for determination of selected organophosphorus pesticides in post Mortem Tissues by GC-NPD

A method for determination of selected organophosphorus pesticides (OPs) along with their degradation products in post mortem tissues is reported in the paper. Malathion, Dimethoate and Phorate are frequently found organophosphates in homicidal or suicidal poisoning cases. The separation of these pesticides along-with their oxon degradation products Malaoxon, Omethoate and Phorate-sulfone respectively is achieved by a programmed temperature capillary column gas chromatography coupled with a nitrogenphosphorus detector (NPD). Prior to analysis, pesticide residues were extracted by QuEChERS extraction method. Matrix matched calibration curves were linear with coefficients of correlation better than 0.995 for concentration range from 0.5 to 20 μg/gm while the limits of detection ranged from 0.05 to 0.85 μg/gm for all compounds. The method is simple, rapid and was used to detect the oxon degradation products of the original OP which otherwise were not detectable by other conventional methods used for routine analysis of post-mortem tissues in poisoning cases.

Clinical and Laboratory Profile of Patients Admitted with Cleistanthus Collinus Poisoning in a Tertiary Care Hospital

Cleistanthus collinus (Oduku) is a common suicidal poison used in rural southern India. There is paucity of information on human studies about this poisoning at global level. We conducted a cross-sectional observatory study to analyse clinical and laboratory profile of patients admitted with Oduku poisoning in Department of General Medicine, Government medical college, Thrissur over a period of one year from 1st January 2013 to 31st December 2013.Out of the 143 cases of plant poisoning, study population consisted of76 (53%)patients who consumed Oduku. Mean age of the population was 33.5 years (+/-SD 16.10). 43 patients (57.33%) were asymptomatic; among those with symptoms, 41 patients (54.67%). had nausea, 33 patients (44.00%) had vomiting, 7 patients (9.33%) had abdominal pain, 1 patient (1.33%) had palpitation and altered sensorium. Hypokalemia was found in 15 patients (19.74%) on admission, 7 patients (9.33%) after 24 hours and 8 patients (10.67%) after 48 hours. ECG changes observed were ST depression (23.68%), T inversion (23.68%) and u waves (17.11%). Mortality rate of Oduku poisoning found in this study was 2.63% (n=2) and expired patients showed persistent hypokalemia despite treatment. Oduku plant constitutes a major agent of DSH among the plant poisons in South India. Gastrointestinal, cardiovascular and neurological symptoms are common with oduku poisoning. Hypokalemia and ECG changes are seen, but mortality rate is low.

Uncontrolled seizures and unusual rise in leucocyte counts: transfluthrin, liquid mosquito repellent suicidal poisoning.

Transfluthrin is being used as fast acting insecticide and liquid mosquito repellent. This is a case report of poisoning with transfluthrin (90 ml liquid containing 792 mg of transfluthrin) by a 25-year-old female. Tonic-clonic convulsions were not controlled with conventional drugs. In intensive care unit, patient was managed with muscle paralysis by neuromuscular blocking drug vecuronium and elective mechanical ventilation for more than 48 h under care of the anaesthesiologist with uneventful recovery.

Why lifespans are more variable among blacks than among whites in the United States.

Lifespans are both shorter and more variable for blacks than for whites in the United States. Because their lifespans are more variable, there is greater inequality in length of life-and thus greater uncertainty about the future-among blacks. This study is the first to decompose the black-white difference in lifespan variability in America. Are lifespans more variable for blacks because they are more likely to die of causes that disproportionately strike the young and middle-aged, or because age at death varies more for blacks than for whites among those who succumb to the same cause? We find that it is primarily the latter. For almost all causes of death, age at death is more variable for blacks than it is for whites, especially among women. Although some youthful causes of death, such as homicide and HIV/AIDS, contribute to the black-white disparity in variance, those contributions are largely offset by the higher rates of suicide and drug poisoning deaths for whites. As a result, differences in the causes of death for blacks and whites account, on net, for only about one-eighth of the difference in lifespan variance.

Prevalent Poisonings in Adolescents and Adults in Dubai: A Compendium from Rashid Hospital

Background: Profile of acute poisonings varies from country to country depending on the ease of availability of substances and socio-economic condition of people; however, very little information from the United Arab Emirates (UAE) have been published, so far. This study was designed to find out the most common causes of overdose and poisoning in patients admitted to the emergency department of Rashid Hospital (RH), Dubai, UAE. Methods: In this retrospective cross sectional study, medical records of poisoned patients admitted to RH from 1st January 2012 to 31st December 2012 were reviewed. Demographic data, types of substances used, intention, length of hospital stay and outcomes were recorded in pre-designed checklists. Results: Overall, 163 patients were studied that among them gender distribution was relatively equal (male: female = 1.04: 1). Mean age of patients was 30.3 ± 11.5 and most patients were in the age group of 20 to 29 years age old (41.7%). Rgarding the type of poisons, the majority of patients were poisoned with pharmaceuticals (55.8%) followed by chemical substances (23.3%). In pharmaceutical poisonings, most cases were due to multi-drug ingestion (22.6%), followed by ingestion of paracetamol (14.1%) and benzodiazepines (4.3%). Considering the gender distribution, women were significantly more involved with pharmaceutical poisoning (P = 0.046), while venomous envenomation occurred only in men indicating a significant difference (P = 0.004). In chemical poisoning, most cases were due to ingestion of corrosive agents (19%). Suicidal poisoning was significantly more common in women (P < 0.001), while abuse was significantly more common in men (P < 0.001). Length of hospital stay averaged on 8.1 days. Only 3 patients died during the admission (mortality rate: 1.8%). Conclusion: Study on, training for and prevention of poisoning should receive more attention in the UAE. Over-the-counter drugs especially paracetamol should be prescribed in a more controlled manner.

PROFILE OF ACUTE POISONING CASES TREATED IN A TERTIARY CARE HOSPITAL: A STUDY IN NAVI MUMBAI

Background: Periodic epidemiological studies are necessary to understand the pattern of poisoning in each region. This study was designed to evaluate the pattern of acute poisoning cases treated in a tertiary care hospital in Navi Mumbai, India. Methods: This cross sectional study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre during July 2012 to July 2013. All cases of poisoning admitted to the hospital were included in this study. The patients’ data were obtained from medical records and were documented on a pre-structured proforma. Results: A total of 74 cases of acute poisoning were studied, of which 51.4% were men. Most of the patients aged 20 to 29 years (44.6%). In majority of cases, the route of exposure to poison was oral (86.5%). Most of the patients reside in urban areas (52.7%). Most of the patients were Hindus (85.1%) followed by Muslims (14.9%). The exposure mostly occurred between 6:00 pm to 12:00 am (30% of cases). The majority of poisonings (44.6%) was due to consumption of household products followed by pesticides (14.9%) and pharmaceutical agents (13.5%). Neurologic manifestations were the most common clinical findings (64.8%) followed by gastrointestinal manifestations (37%). All patients were treated successfully with no mortality. There was a significant correlation between gender and intention of poisoning (P < 0.001), as the suicidal attempts were higher in women (69.4%). Moreover, a significant relationship existed between marital status and intention of poisoning (P = 0.016) as the suicidal poisonings were most common among married individuals (45.7%). Conclusion:The trend in poisoning is never static. Household products were identified as the main cause of poisoning in urban areas of India. Educational programs with more emphasis on preventive measures are necessary to create awareness among the general public. How to cite this article: Patil A, Peddawad R, Verma VCS, Gandhi H. Profile of Acute Poisoning Cases Treated in a Tertiary Care Hospital: a Study in Navi Mumbai. Asia Pac J Med Toxicol 2014;3:36-40.

Activation of PI3K/Akt signaling in rostral ventrolateral medulla impairs brain stem cardiovascular regulation that underpins circulatory depression during mevinphos intoxication

As the most widely used pesticides in the globe, the organophosphate compounds are understandably linked with the highest incidence of suicidal poisoning. Whereas the elicited toxicity is often associated with circulatory depression, the underlying mechanisms require further delineation. Employing the pesticide mevinphos as our experimental tool, we evaluated the hypothesis that transcriptional upregulation of nitric oxide synthase II (NOS II) by NF-κB on activation of the PI3K/Akt cascade in the rostral ventrolateral medulla (RVLM), the brain stem site that maintains blood pressure and sympathetic vasomotor tone, underpins the circulatory depressive effects of organophosphate poisons. Microinjection of mevinphos (10nmol) bilaterally into the RVLM of anesthetized Sprague-Dawley rats induced a progressive hypotension that was accompanied sequentially by an increase (Phase I) and a decrease (Phase II) of an experimental index for the baroreflex-mediated sympathetic vasomotor tone. There were also progressive augmentations in PI3K or Akt enzyme activity and phosphorylation of p85 or Akt(Thr308) subunit in the RVLM that were causally related to an increase in NF-κB transcription activity and elevation in NOS II or peroxynitrite expression. Loss-of-function manipulations of PI3K or Akt in the RVLM significantly antagonized the reduced baroreflex-mediated sympathetic vasomotor tone and hypotension during Phase II mevinphos intoxication, and blunted the increase in NF-κB/NOS II/peroxynitrite signaling. We conclude that activation of the PI3K/Akt cascade, leading to upregulation of NF-κB/NOS II/peroxynitrite signaling in the RVLM, elicits impairment of brain stem cardiovascular regulation that underpins circulatory depression during mevinphos intoxication.

Comparative analysis of suicidal poisoning autopsied at the Institute of forensic medicine in Belgrade

Number of poisons which surround the modern man is constantly on the rise and hence therefore the frequency of intoxication. The aim of the study was to determine the type of poison which causes the suicidal poisoning, sex, age, occupation, place of poisoning, events and seasonal distribution of poisoned. This paper analyzes the suicidal poisoning, autopsied at the Institute of Forensic Medicine in Belgrade in two periods (1965-1969) and (2000-2004) years . To test for statistical significance was used Pearson's X2 test. Comparative analysis of the obtained results shows that a significantly more frequent suicidal poisoning in the first analyzed period (1965-1969), P<0.01 compared to the second (2000-2004) In the first research period, the suicidal purposes are often used caustic poisons (44.0%) and drugs (36.4%) with a slight dominance of the older age groups among the poisoned. According to the frequency of poisoning drugs no statistically significant differences in the analyzed periods (x2=0.248 , df=1, p=0.6) . In second research period, significantly dominated by males (79.5%) (x2=33.911 , df=1, p<0.0001), younger age groups (20-49 years , 86.99%), which were poisoned significantly more frequent in spring and summer (55%) compared to the first period. In both studied periods had no significant statistical difference in relation to occupation, place of poisoning and the clinical picture. The highest percentage of deaths (servants and housewives) in both periods were without clinical picture, because they were found dead in their own homes. Length of outliving period of several hours is significantly higher in the second examined period, because of application of more sophisticated, more toxic and simple to use poisons.

Acute poisoning in children; changes over the years, data of pediatric clinic department of toxicology

ObjectiveTo present the frequency, etiology, changes over the years of acute poisoning in children admitted to Pediatric Clinic of Pristina and to determine the extent and characteristics of the problem, according to which related preventive measures can be taken. MethodsRetrospectively we have analyzed the epidemiology of accidental and suicidal poisonings in children hospitalization in Pediatric Clinic Department of Toxicology during the year 2012. Our data we compared with data from previous studies on acute poisoning in children in the Pediatric Clinic conducted during the years 1976–1985 and 2001. ResultsDuring the year 2012, in Pediatric Clinic of Pristina 5 723 children were hospitalized, 136 of them or 2.3% were treated due to acute poisoning in Department of Toxicology, 82 of them was boys and 54 was girls, rate boys girls was 1.5:1. The majority of cases 101 or 74.2% were under five years with peak age three and 35% or 25.7% were over five years. The most of the cases was accidentally 97% and only 2.9% was suicidal and all of them were over the age of ten. Drugs were the most common agent causing the poisoning 71 (52.2%) followed by house cleaning products 38 (27.9%), food 10 (5.8%), pesticides 7 (5.14%), rare agent that caused poisoning were: narcotic substances, plant, heavy metals, alcohol, carbon monoxide, carburant. Poisoning occurred mostly in spring and the peak was observed in May, (1.17% of all patients). January was the month of lowest rate of poisoning. During the years 1976–1985, in Pediatric Clinic of Pristina 900 children were hospitalized due to acute poisoning, 44.11% were from drugs, 15.88% from pesticides, 65 (7.2%), while during 2001 in the unit care intensive were hospitalized 66 children due to acute poisoning, among them 51.5% were poisoning from drugs, 30.03 from pesticides, 12.2% from cleaning products. ConclusionIn our study drugs and house cleaning products are the most frequent agents causing accidental poisoning in children less than 5 years-old, this age of children is the most susceptible in terms of morbidity. Compared with the previous studies in Pediatric Clinic of Pristina, drugs are still the most frequent cause of acute poisoning in children; the number of poisoning with pesticides has fallen but has increased the number of poisoning with cleaning products. All preventive measures against poisoning should be taken including preventive strategies of education at national level especially in drug and household product storage.

Clinical profile of celphos poisoning in central India

Background: Celphos poisoning (trade name of aluminium phosphide) is a large, though under-reported, problem in the Indian subcontinent. Methods: The study was conducted at the Intensive Care Unit (ICU) of a tertiary care teaching hospital of central India. Data were collected by a retrospective chart review of all patients admitted from February 2010 to February 2014 with a diagnosis of celphos poisoning. Results: Fifty patients (32 females, 18 males) were registered from the 967 patients of poisoning admitted to the ICU during the same period, of whom 44 (88%) had died (non-survivors) and the remaining 6 (12%) had survived. Forty five cases were of suicidal poisoning, and 5 were of accidental poisoning. Majority [42/50 (84%)] were from rural background. The ingested dose was 7.23 ± 1.28 gram among non-survivors and 3.3 ± 1.9 gram among survivors. Conclusion: Strict implementation of nationwide pesticide regulation, including restricting the availability of poison, being aware of its toxicity and providing improved medical management in consultation with regional or national poison control centers could further reduce the mortality due to ALP toxicity as there is no antidote available presently.

Identifying probable suicide clusters in wales using national mortality data.

BackgroundUp to 2% of suicides in young people may occur in clusters i.e., close together in time and space. In early 2008 unprecedented attention was given by national and international news media to a suspected suicide cluster among young people living in Bridgend, Wales. This paper investigates the strength of statistical evidence for this apparent cluster, its size, and temporal and geographical limits.Methods and findingsThe analysis is based on official mortality statistics for Wales for 2000–2009 provided by the UK's Office for National Statistics (ONS). Temporo-spatial analysis was performed using Space Time Permutation Scan Statistics with SaTScan v9.1 for suicide deaths aged 15 and over, with a sub-group analysis focussing on cases aged 15–34 years. These analyses were conducted for deaths coded by ONS as: (i) suicide or of undetermined intent (probable suicides) and (ii) for a combination of suicide, undetermined, and accidental poisoning and hanging (possible suicides). The temporo-spatial analysis did not identify any clusters of suicide or undetermined intent deaths (probable suicides). However, analysis of all deaths by suicide, undetermined intent, accidental poisoning and accidental hanging (possible suicides) identified a temporo-spatial cluster (p = 0.029) involving 10 deaths amongst 15–34 year olds centred on the County Borough of Bridgend for the period 27th December 2007 to 19th February 2008. Less than 1% of possible suicides in younger people in Wales in the ten year period were identified as being cluster-related.ConclusionsThere was a possible suicide cluster in young people in Bridgend between December 2007 and February 2008. This cluster was smaller, shorter in duration, and predominantly later than the phenomenon that was reported in national and international print media. Further investigation of factors leading to the onset and termination of this series of deaths, in particular the role of the media, is required.

Correlation between Cholinesterase and Paraoxonase 1 Activities:Case Series of Pesticide Poisoning Subjects.

Acute exposure to pesticide due to suicidal poisoning is the most extensive cause of pesticide exposure, compared with all other causes including agricultural or industrial exposure. Organophosphate (OP) and carbamate group of pesticides can inhibit acetylcholinesterase; on the other hand, paraoxonase1 can detoxify organophosphate poisoning by hydrolyzing organophosphate metabolites. We have compared the serum paraoxonase1 status and cholinesterase activity of subjects who attempted to commit suicide by consuming OP pesticide. Cholinesterase and paraoxonase1 activity were measured spectrophotometrically using butyrylthiocholine and phenyl acetate as substrates, respectively. A positive correlation was found between serum paraoxonase1 activity and cholinesterase activity among pesticide consumed subjects. Our results suggest that subjects with higher paraoxonase1 activity may have a better chance of detoxifying the lethal effect of acute organophosphate poisoning.

Suicides par intoxication dans la région de Souss-Massa-Drâa au Maroc

Deliberate self-poisoning is a serious problem in Morocco, including in the Souss-Massa-Drâa region. However, our understanding of the problem of suicidal poisoning remains limited. This paper aims to describe the characteristics of patients, toxic substances and poisoning and to identify the risk factors influencing patient outcomes. A retrospective study was conducted of all cases of deliberate self-poisoning recorded between 1981 and 2007 by the Centre Anti-Poison et de Pharmacovigilance du Maroc. 1,130 cases of self-poisoning were identified. The mean age was 25 ± 10.1 years and the sex ratio was 0.4. Paraphenylenediamine was the most common cause of death (48 deaths), followed by hydrochloric acid (15 deaths). A close relationship was found between progression to healing and female adolescents and between progression to death and men in other age groups. The study also found that patients who used paraphenylenediamine were twelve times more likely to die (CI95%: 7.4%-19.2%) than those who used other substances. Patients with respiratory and cardiovascular conditions had a relative risk of 9.8 (CI95%: 6.3%-16%) and 3.6 (CI95%: 2.3%-5.7%). Of the 937 cases with known outcome, 89 died (9.5%).

Parasuicidal poisoning by intramuscular injection of insecticide: A case report

Suicidal poisoning by ingestion of organophosphate (OP) insecticides represents a serious emergency with a high mortality rate. However, attempted suicide via the parenteral route has rarely been reported. The present study reports a case of parasuicide by self-injection of an organophosphorus insecticide (phoxim, phenylglyoxylonitrile oxime O,O-diethyl phosphorothioate) into the distal region of the left arm. The patient developed necrosis at the injection site and an abscess of the affected limb following injection. A fasciotomy and surgical debridement resulted in the symptoms of the patient disappearing within a few days and were vital in shortening the course of the disease.

Transition From Oxidative Stress to Nitrosative Stress in Rostral Ventrolateral Medulla Underlies Fatal Intoxication Induced by Organophosphate Mevinphos

As the most widely used pesticides in the world, fatal incidence of suicidal poisoning by organophosphate compounds is high and is often associated with cardiovascular toxicity. Using the pesticide mevinphos as our tool, we investigated the roles of oxidative stress and nitrosative stress at the rostral ventrolateral medulla (RVLM), the brain stem site that maintains arterial pressure (AP) and sympathetic vasomotor tone, in the cardiovascular depressive effects of organophosphate poisons. Microinjection of mevinphos (10 nmol) into the RVLM of anesthetized Sprague-Dawley rats induced progressive hypotension that was accompanied by an increase (phase I), followed by a decrease (phase II) of an experimental index of baroreflex-mediated sympathetic vasomotor tone, with a fatality rate of 35%. During phase I, there was a preferential upregulation of angiotensin type I receptor (AT1R) messenger RNA (mRNA) and protein that leads to activation of NADPH oxidase (Nox) and increase in superoxide at the RVLM. Pharmacological antagonism of these signals exacerbated fatality and shorted survival time by eliminating baroreflex-mediated sympathetic vasomotor tone, AP, and heart rate. During phase II, there was a progressive upregulation of angiotensin type II receptor (AT2R) mRNA and protein that leads to increase in peroxynitrite in the RVLM, blockade of both sustained brain stem cardiovascular regulation and improved survival. We further found that AT1R and AT2R cross-interacted at transcriptional and signaling levels in the RVLM. We conclude that a transition from AT1R-mediated oxidative stress to AT2R-mediated nitrosative stress in the RVLM underlies the shift from sustained to impaired brain stem cardiovascular regulation that underpins cardiovascular fatality during mevinphos intoxication.