Organophosphorus Poisoning: an Overview

International Journal of Health Sciences and Research www.ijhsr.org ISSN: 2249-9571

Review Article

Organophosphorus Poisoning: An Overview

Singh Yatendra1, Subhash Chandra joshi2, Makrand Singh2, Arun Joshi2, Jainendra Kumar3

1Assistant Professor, 2Associate Professor, 3Post Graduate Resident, Department of Medicine, Government Medical College, Haldwani, Uttarakhand (India).

Corresponding Author: Singh Yatendra

Received: 24/06//2014 Revised: 23/07/2014 Accepted: 24/07/2014

ABSTRACT

Organophosphorus pesticides are used widely for agriculture, vector control, and domestic purposes. Despite the apparent benefits of these uses acute organophosphorus pesticide poisoning is an increasing worldwide problem, particularly in rural areas. Their toxicity has been recognised since the 1930s, when they were also developed for use as chemical warfare agents. Our aim is to provide an evidence based review of the pathophysiology, diagnosis and management of acute organophosphorus pesticide poisoning. We emphasize that in future, especially in developing countries, Government authorities should be encouraged to control organophosphate product licensing, manufacture, storage, import, methods of use and delivery, food contamination and disposal.

Key words: Atropine, Organophosphorus poisoning, Pesticide, pralidoxime

Key Messages: In developing countries, especially in India, organophosphorus pesticide use is widespread as most population is mainly rural with farming as a major occupation. Acute poisoning is a medical emergency. It is important to know the nature, severity and outcome of acute poisoning cases in order to take up appropriate planning, prevention and management techniques.

INTRODUCTION octomethyl pyrophosphotetramide (OMPA). Organophosphorus (OP) compounds [2-4] Some OP esters are still used to treat have been widely used for a few decades in glaucoma (Ecothiopate). In addition to these agriculture for crop protection and pest beneficial agricultural, veterinary, and control, thousands of these compounds have medical uses, some highly potent OP been screened and over one hundred of them anticholinesterase compounds, including have been marketed for these purposes. [1] tabun, sarin, soman, and VX have been used Some have also been used in the medical as “nerve gases” in chemical warfare. They treatment of myasthenia gravis, e.g. are also been used as plasticizers, stabilizers diisopropyl phosphorofluoridate (DFP), in lubricating and hydraulic oils, flame tetraethyl pyrophosphate (TEPP) and retardants, and gasoline additives. [5]

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Acute poisoning is an important management of organophosphorous cause of morbidity and mortality in poisoning with emphasis on optimization developing countries like India. In medical and monitoring of usage of OP compounds. emergency 10% of admissions are due to Epidemiology: poisoning and organophosphorus poisoning The organophosphate compounds are contributes to nearly 50% of it. [6] most commonly associated with serious Acute poisoning with human toxicity, accounting for more than organophosphate compounds is common in 80% of pesticide-related hospitalizations. [11] northwest India and is generally as a result In contrast to the past, when chlorinated of suicidal ingestion. In India, hydrocarbon compounds such as DDT were Organophosphorus compounds (OPCs) are commonly used, organophosphate freely available in shops and widely used as insecticides have become increasingly insecticides in agriculture and at home. In popular for both agricultural and home use the past, a high mortality was reported but in because their unstable chemical structure recent years, with intensive care, mortality leads to rapid hydrolysis and little long-term has considerably declined. [7] accumulation in the environment. [12] A Organophosphates cause poisoning recent national survey in Bangladesh by inhibition of the enzyme cholinesterase showed that 14% of all deaths (3971 of with subsequent accumulation of 28,998) of women between 10 and 50 years acetylcholine and symptoms relating to of age were due to self-poisoning, the overactive cholinergic action. The majority with pesticides. [13] mechanism of inhibition is phosphorylation The importance of pesticides in India of the esteratic locus on the enzyme with the can be understood from the fact that formation of a stable chemical complex agriculture is a major component of the which is biologically inactive. Indian economy: It contributes 22% of the In parts of developing world nation’s GDP and is the livelihood of nearly pesticide poisoning causes more deaths than 70% the country’s workforce. Globally, due infectious diseases. [7] Organophosphate to consolidation in the agrochemical insecticides account for more than 50% of industry, the top five multinational all acute poisoning in hospital practice, the companies control almost 60% of the majority of patients are younger than 30 yrs. market. [8] In teenagers and adults the poisoning is Overexposure to pesticides can occur generally due to suicidal intention although before spraying– because of easy access for accidental poisoning during spraying can children, lack of adequate labeling and also occur. [9] during mixing – during spraying and after Mortality ranges from 4% to 38% in spraying operations. Spray operators and Indian studies. The most common cause of bystanders can be affected. Having cheap death is respiratory failure. Early recognition and easily available highly hazardous and prompt ventilator support may improve pesticides at hand increases the incidence of the survival rate. The common use of intentional pesticide poisonings. [14] insecticides in public health and agricultural The effective number of cases of schedules has caused severe environmental pesticide poisoning occurring in India pollution and potential health hazards annually has been estimated by G. Ravi et al including severe acute and chronic cases of 2007 to be up to 76 000, much higher than human and animal poisonings. [10] So our the figure of NCRB. Furthermore, Gunell et aim is to discuss the clinical features and al, 2007 calculate that the number of International Journal of Health Sciences & Research (www.ijhsr.org) 246 Vol.4; Issue: 8; August 2014 intentional cases alone reaches some serum cholinesterase 126,000 cases annually. [15] The reasons for (pseudocholinesterase). [19] the suicide in males may include lack of Normally the cholinesterases rapidly employment, poverty, urbanization and hydrolyze the neurotransmitter acetylcholine various other stress related factors. In into inactive fragments of choline and acetic females, it may be due to marital acid after the completion of neurochemical disharmony. [16] transmission. The neurotransmitter CLASSIFICATION AND BIOLOGICAL acetylcholine is present in the terminal ASPECTS OF ORGANOPHOSPHORUS endings of all postganglionic COMPOUNDS: parasympathetic nerves, at myoneural Classification [9,17] junctions, and at both parasympathetic and Organophosphorus compounds are classified sympathetic ganglia. The major toxicity of as organophosphate compounds is the covalent I. By chemical structure: binding of phosphate radicals to the active A. Alkyl phosphates: HETP (Hexaethyl tetra sites of the cholinesterases, transforming phosphate), TEPP (tetraethyl them into enzymatically inert proteins. [19,20] pyrophosphate) tetron, fosvex etc Organophosphates thus act as irreversible B. Aryl phosphates : Paroxon (0,0, diethyl- cholinesterase inhibitors because the o-p-nitrophenyl phosphate) –E 600- organophosphate-cholinesterase bond is not mintacol, Parathion (0,0, diethyl-o-p- spontaneously reversible without nitrophenyl thiosulphate or diethyl pharmacological intervention. The inhibition thiophosphoric ester of p-nitrophenol-folidol of cholinesterase activity leads to the (bayer), Eketox (sandoz), kilphos, niran, accumulation of acetylcholine at synapses, rhyntox, oriental Bug’s bait etc. causing overstimulation and subsequent II. By toxicity [18] disruption of transmission in both the central Highly toxic (< D50 < 50mg/kg): and peripheral nervous systems. Exposure to Azinophos-methyl (Cruthion), Bomyl organophosphate compounds will, therefore, (Swat) interfere with synaptic transmission Carbophenthion (Trithion) etc. peripherally at muscarinic neuroeffector Moderate Toxicity (αD50 = 50-1000mg/kg): junctions and nicotinic receptors within Acephate (Orthene), Bensulide (Betasan), sympathetic ganglia and at skeletal Chloropyrofos (Durshan, Lorsban) etc. myoneural junctions. This is accomplished Low toxicity (αD50 = > 1000mg/kg) : by an overstimulation of acetylcholine Bromophos (Nexagan), Etrimfos (Ekanet), receptor sites that leads to a variety of Iodofenphos (Nuvanol N) etc. physiologic and metabolic derangements. (αD50 = lethal dose in experimental Disruption of transmission also will occur at animals) the acetylcholine receptor sites within the central nervous system. [20] MECHANISM OF ACTION: Organophosphate compounds avidly MODE OF INTOXICATION: [18,20,21] bind to cholinesterase molecules and Most OP compounds are extremely share a similar lipophilic. They are therefore readily chemical structure. In human beings, the two absorbed by passive diffusion across lung principal cholinesterases are RBC, or true and gastrointestinal system or skin. cholinesterase (acetylcholinesterase), and Deliberate ingestion is common with suicidal intensions in developing countries, International Journal of Health Sciences & Research (www.ijhsr.org) 247 Vol.4; Issue: 8; August 2014 where they are readily available and cheap. administration. Metabolism is mainly due to Dermal and mucous membrane absorption is oxidation, by cytocrome-p-450 system and slower but clinical poisoning can occur after hydrolysis of ester bonds mediated by prolonged exposure. Inhalation by accident various esterases or paroxonases. may occur during spraying in improper Elimination mainly occurs via urine and conditions. Intoxication by inhalation may faeces. occur during chemical warfare and Urinary and faecal elimination is following accidents during storage usually rapid, 80-90% of most compounds particularly when stock catch fire. being eliminated within 48 hrs.A very small Kora etal 2011 found that The proportion of OP compounds and their commonest route of poisoning was oral in active forms are excreted unchanged in the suicidal cases and there were 6 urine. Some compounds remain longer in accidental poison cases with 3 cases of body like fenthion and Fenithrothion. inhalational OP poisoning, in which one These compounds and their active required ventilator support. The reasons for metabolites cause toxicity by inhibiting the the suicide in males may include lack of function of acetylcholinesterase, the enzyme employment, poverty, urbanization and responsible for hydrolysing and inactivating various other stress related factors. In the neurotransmitter acetylcholine. They females, it may be due to marital also inhibit number of enzymes belonging to disharmony. [16] the group of carboxyl-esterases. The Distribution and Storage: biological effects of OP compounds are a Following absorption, OP result of accumulation of endogenous acetyl compounds accumulate rapidly in fat, liver, choline at sites of cholinergic transmission. kidneys and salivary glands. The Ion binding is by which enzyme phosphorothioates (P=S), for example AChE is inhibited, but eventually diazonin, parathion, and bromophos, are progressively phosphorelated by covalent more lipophilic than phosphates (P=O), for bonding a process normally takes 24-48 hrs. example dichlorvos, and are therefore stored This process is called “Ageing” and extensively in fat which may account for the this period is known as the “critical interval” prolonged intoxication and clinical relapse because during this time administration of after apparent recovery which has been antidote is still effective in reversing the observed in poisoning from these OP process. Once ageing is completed the insecticides. OP compounds generally are enzyme cannot be reactivated. Plasma AChE lipophilic and therefore cross the blood / recovers quickly within 4 weeks. Red cell brain barrier in most cases. [22] AChE takes longer and may not be restored. Affected AChE recovers at the rate of ~ 1% ORGANOPHOSPHORUS COMPOUND per day. METABOLISM: [8,18,20,23,24] Restoration of AChE activity occurs After absorption in skin, GI tract or by slow denovo synthesis of free enzyme inhalation, the insecticides and their and also to some extent as a result of metabolites gets distributed quickly spontaneous dephosphorylation of the especially in liver kidneys, adipose tissue inhibited enzyme. The inactivation and tissues rich in lipids. The plasma half (phosphorylation) and reactivation life after a single administration is from few (Dephosphorylation) vary considerably with minutes to several hours which depends on different OP compounds, which accounts for type of compound and rate and amount of differences in toxicity. Ageing has an International Journal of Health Sciences & Research (www.ijhsr.org) 248 Vol.4; Issue: 8; August 2014 important bearing on toxicity and treatment ingestion symptoms appear within 30-90 outcome. Organophosphorus compounds minutes and a maximum of 24 hrs in case of inhibit number of other enzymes such as compounds which are highly lipophilic and lipases, trypsin and chymotrypsin which are which require metabolic bioactivation. [18] phosphorylated by these compounds. The Local Effects: rate of reaction is slower compared to AChE GI symptoms appear first before the onset of and clinical consequences are not known. systemic symptoms. In inhalation typically They also affect, central nervous system, exhibits respiratory effects. After ocular cardiovascular system, metabolic and exposure symptoms generally begins in the endocrine system including reproduction eyes. and neuromuscular system. Systemic Effects: The acceptable daily intake: Three well defined clinical phases are The amount of chemical which can be observed- consumed every day for an individual life 1) Initial cholinergic phase. span with the practiced certainty based on 2) The intermediate syndrome (IMS) valuable evidence that no harms will result 3) Delayed polyneuropathy for humans. This is 0.02 mg/kg for THE CHOLINERGIC PHASE [25-31] malathion, and 0.004 mg/kg for parathion. It is mainly due to accumulation of Ach at [20] the cholinergic synapses and may be classified into CLINICAL MANIFESTATIONS: 1) Muscarinic (all postganglionic nerve The clinical manifestation of OP endings) poisoning depends on the agent, quantity 2) Nicotinic (Autonomic ganglia and and route of entry. Ingestion and inhalation skeletal muscle end plates). result in more rapid development of 3) CNS manifestations (synapses in CNS) symptoms than dermal exposure. After

1) Muscarinic manifestations Anatomic site of action Physiological effects a) Bronchial tree Dyspnea, increased bronchial secretions, cough, wheezing and tightness in chest b) GI system Vomiting, diarrhoea, nausea abdominal tightness, cramps tenesmus, faecal incontinence. c) Sweat glands Increased sweating d) Pupils Miosis, occasionaly unequal e) Lacrimal glands Increased lacrimation f) Salivary glands Increased salivation g) Cardiovascular system Hypotension, Bradycardia h) Bladder Frequency, urinary incontinence i) Ciliary body Blurring of vision

2) Nicotinic manifestations : Anxiety, restlessness, giddiness, Of sympathetic ganglia Pallor, Tachycardia emotional liability, slurred speech, ataxia, Hypertension seizures, drowsiness, confusion, difficulty in Of striated muscle Muscle twitchings concentration, headache, nightmare, Cramps Weakness insomnia, excessive dreaming, apathy, Fasciculation tremor, depression, generalized weakness, coma, absence of reflexes, Cheyne – Stokes 3) Central nervous system manifestations:

International Journal of Health Sciences & Research (www.ijhsr.org) 249 Vol.4; Issue: 8; August 2014 respiration, depression of respiratory and Tachycardia and increased blood pressure circulatory centres with Dyspnea, occurs in initial stage and Bradycardia and Hypotension, cyanosis. The combination of low blood pressure in the later stage. symptoms may vary. Commonest effect observed was The predominant clinical finding are tachycardia. usually muscurinic which is followed by 2. Respiratory system [33,34] CNS and then nicotinic manifestations GI Respiratory arrest a common terminal symptoms are first to appear after ingestion. manifestation of OP poisoning is produced [28] by over stimulation of 3 types of receptors. The intermediate syndrome (IMS): It can be recalled that muscarinic action After apparent recovery from produces increased bronchial secretions, cholinergic crisis muscle paralysis occurs, Bronchoconstriction leading to pulmonary but before the expected onset of the delayed oedema and chest tightness. On other hand polyneuropathy has been identified as nicotinic action produce intercostal muscle “Intermediate syndrome (IMS). This is type paralysis and respiratory muscle weakness II paralysis first described by Wadia et al. leading to respiratory paralysis. [21] In 1974 and later christened as 3. Altered immunity to infection [35] “Intermediate syndrome” (IMS) by The immunosuppression is associated with Senanayake, Karalliedde L. [22] The severe cholinergic stimulation either from a syndrome is of Acute onset, seen within 24- direct action of acetylcholine on the immune 96 hrs (1-4 days) after poisoning, affecting system or secondary to toxic chemical stress conscious patients without fasciculations or associated with cholinergic poisoning. other cholinergic manifestations. The 4. Gastrointestinal system [36] cardinal features of this syndrome is muscle After ingestion of organophosphate weakness affecting predominantly proximal compound the initial symptoms may be limb muscles and neck flexors. [24,25] increased salivation, nausea, vomiting, Delayed polyneuropathy [8,20,25,27] abdominal tightness and cramps are the Though uncommon in India the commonest. Other muscarinic neuropathy develops following a latent manifestations include diarrhea, tenesmus period of 2-4 weeks after the cholinergic and faecal incontinence. crisis. The main clinical features are 5. Effects on reproduction weakness of distal muscles of feet and hand. Following organophosphorus poisoning in The weakness is preceded by pain and females abortions were being reported. parasthesia of limbs. Wasting of distal In late 20th century, several experimental muscles of particularly small muscles of the and epidemiological studies regarding hand and those of anterior and peroneal hormonal imbalance especially sex compartments of the leg is an inevitable hormones leading to adverse developmental consequence. In some patients pyramidal outcomes related to pesticide exposure, tract signs appear after a few weeks or few including foetal death, intrauterine growth months. Recovery is variable. restriction, congenital malformations and The phosphorylation of an enzyme male / female fertility have been published. neuropathy target esterase in nervous tissue 6. Effects on temperature regulation [20] is considered to be responsible for the It has been noted in several case studies with polyneuropathy. incidence of 7% of derangement of OTHER EFFECTS OF OP POISONING temperature regulation in the form of 1. Cardiovascular system [29-32] International Journal of Health Sciences & Research (www.ijhsr.org) 250 Vol.4; Issue: 8; August 2014 hypothermia. Some may experience fever distinguishes the IMS from the delayed lasting for many days a biphasic response. polyneuropathy, which appears 2-3 weeks 7. Vocal card paralysis [20] after poisoning. In few patients vocal card paralysis was 3) Delayed polyneuropathy reported within 2 days. History of intoxication with OP agents and 8. Effects on other systems [20] the time of onset and distribution of muscle Eyes : myopia and pigmentary degeneration weakness differentiate from other causes of of retina. acute polyneuropathy. Joints : arthritis, cerebellar ataxia. Interference with mitochondrial oxidative MANAGEMENT metabolism. 1. ACUTE CHOLINERGIC CRISIS [20,24] 9. Changes in metabolism and endocrine All patients should be managed as activity [37,38] emergencies in hospital. Transient hyperglycaemia and glycosuria are A. First aid often found in severe OP poisoning. B. Prevent further absorption of insecticide Absence of acetone bodies differentiates C. Specific antidote therapy from diabetic coma, except for coma in • Anticholinergic medication diabetic patients due to hyperosmolarity • Reactivation of Acetylcholine-oximes from excessive blood glucose. D. Benzodiazepines A. First Aid: DIAGNOSIS a) Remove patient from the contaminated 1) Acute cholinergic crisis [24,39-41] – made environment. on b) Remove contaminated clothing • History of ingestion of the compound c) Wash skin with soap and water and eyes • Signs and symptoms with water • Improvement after atropine and oxime d) Assess breathing and circulation therapy e) Resuscitate if necessary • Inhibition of cholinesterase activity f) Support vital functions if necessary Organophosphate poisoning is generally • O2 inhalation diagnosed clinically based on the • Lung ventilation characteristic symptoms and the history of • Ionotropes exposure to OP agents. When diagnosis is g) Control of convulsions not evident, a depressed serum or RBC h) Monitor ECG, blood pressure, O2 cholinesterase level is helpful (<50%). If OP saturation, ventilation, level of poisoning is suspected therapy should never consciousness. be withheld pending confirmation of lab B. Prevent further absorption of values. insecticide: 2) Intermediate syndrome a) Gastric lavage: The diagnosis is clinical and should be Gastric lavage is often the first intervention suspected when a patient who is recovering poisoned patients receive on presentation to from the cholinergic crisis develops hospital, sometimes at the expense of respiratory difficulty. The presence of resuscitation and giving antidote. No muscle weakness in the absence of muscle evidence shows any form of gastric fasciculations and other cholinergic features decontamination to benefit patients poisoned differentiates it from cholinergic crisis. The with OP. gastric decontamination should early onset of muscle weakness only be done after the patient has been International Journal of Health Sciences & Research (www.ijhsr.org) 251 Vol.4; Issue: 8; August 2014 stabilized and treated with oxygen, atropine maintain this effect for at least 24-48hrs, and an oxime. [42] carefully withdrawn once the patient is Performed using largest possible oro-gastric adequately stabilized, observed for 72 hrs tubes with 50-100ml of fluid / lavage, following termination of atropine before preferably within one hour of ingestion discharge from the hospital. protect airway in patients with impaired The patient should be oxygenated prior to consciousness. atropine administration in order to prevent b) Administer activated charcoal: ventricular dysarrhythmias associated with dose initial 60-100gms, followed by hypoxia. The end point of anticholinergic 0.25gms to 0.50gms/kg every 1-4 hrs. treatment is clearing of secretions from C. Specific antidotal therapy: tracheobronchial tree and drying of most Treatment aims: secretions. a) Reversal of synaptic biochemical Pupillary dilatation is an early response to abnormalities atropine, but it is not a therapeutic end point. b) Reversal of cholinesterase blockade Tachycardia is not a contraindication to This is achieved by administering sufficient atropine. Diaphragmatic muscle weakness is quantity of two complimentary medications. important contributor to hypoventilation and i) Anticholinergic medications – atropine or it is not reversible with atropine. glycopyrrolate Atropine crosses the blood brain barrier and ii) Reactivation of AChE – oximes may cause severe toxic effects such as i) Anticholinergic medications: confusion, psychosis, coma, seizures, Atropine [6,20,23,41,43,44,45,47] delirium, hallucinations, fever tachycardia It is a tertiary amine, a competitive and ileus. antagonist of acetylcholine at muscuranic The studies concluded that patient who post synaptic membrane and in the CNS. In receive aggressive heavy dose of atropine, symptomatic poisoned adults, atropine is survived more frequently than those who given as 1-2mg IV or IM (0.02 – 0.05mg/kg received inadequate doses or none at all. in children). If there is no effect within 10 Also studies observed that continuous high minutes, the dose is doubled every 5 to 10 dose atropine infusion is more effective than minutes, until muscurinic symptoms are intermittent bolus doses. relieved. The action of 2mg atropine Glycopyrrolate [43,46,48,49] sulphate begins 1 to 8 minutes after IV, IM, It is a quaternary ammonium compound may administration, respectively and it is be substituted for atropine in patients with a maximal at 6 to 15 minutes. Half life clear sensorium, with no evidence of central elimination is 2-5 hrs. toxicity. It has many advantages over Alternatively atropine can also be given by atropine such as Better control of secretions, continuous infusion. Atropine 30mg in Lesser tachycardia, Fewer CNS side effects 200ml of NS-at the rate of 0.02-0.08 and Fewer respiratory infections . Dose 0.05 mg/kg/hour – titrate against the important mg/kg Or given at increments of 0.25mg parameters for adequate atropinization, repeated every 5-10 minutes until supplemented by giving additional IV anticholinergic over activity is reversed or boluses of atropine 1-5mg to regain quick upto maximum of 2.5mg/d. control of secretions or severe bradycardia ii) Reactivation of AChE – OXIMES when indicated. [20,23,50,51] Once signs of adequate atropinization Derivatives of hydroxamic acid and a occurs the dose should be adjusted to number of other oximes were shown to International Journal of Health Sciences & Research (www.ijhsr.org) 252 Vol.4; Issue: 8; August 2014 reactivate cholinesterase inhibited by Recognition of OPP and correct initial organophosprus compounds. WHO treatment in hospitals and by general recommends that oxime is given to all practitioners, with early referral of serious symptomatic patients who need atropine. cases can be of vital importance in Mode of action determining prognosis. Treatment of 1) Functions by nucleophilic attack on the seriously ill patients in an ICU is important phosphorylated enzyme, removing the bulky for many reasons, including good phosphate moiety and completely restoring observation to assess the need for ventilator normal acetylcholinesterase activity. support and intensive nursing care. [53] 2) Direct reaction and detoxification and Patients with moderate to severe unbound the OP molecules. organophosphorus pesticide poisoning 3) Endogenous anticholinergic effect in usually require management in an intensive normal doses. care unit. Mortality from severe poisoning is Dose- 1gm every 8-12 hrs IV in adults and high (10%) compared with the overall 25-50mg/kg in children. mortality from pharmaceuticals (0.5%). Maintenance and duration of treatment: Current evidence suggests that prompt and Average duration of treatment 5 to7days. [8] appropriate management optimises The therapeutic concentration of the oximes outcomes. [54] should be maintained to regenerate as much Patients with moderate or severe active enzyme activity as possible until the organophosphorus poisoning should be OP compound has been eliminated. [20] admitted to an intensive care unit after OP residues that are present may bind the resuscitation to allow careful titration of circulatory free PAM and lower its serum antidotes, intubation, ventilation, and concentrations. Therefore PAM should be inotropes or vasopressors if required. [55] continued as long as nicotinic symptoms 3. MANAGEMENT OF DELAYED persist, [28] those who develop the IMS are POLYNEUROPATHY given the drug for longer periods until they .No specific drug therapy is useful. are weaned from ventilatory care. [8] Role of antioxidants in OP poisoning: The Delayed clinical manifestations occur with toxicity of OP compounds is mediated by fat soluble organophosphates like fenthion, generation of nitric oxide and other free chlorfenthion and parathion. Cardiac and radicals. These toxic molecules can be respiratory arrest have known to occur. [30,41] counteracted by antioxidants such as Cardiac monitoring and blood pressure vitamins C and E, spin traps, melatonin and monitoring are advised during and for low molecular weight thiols. The latter several hours after the infusion of oximes. compounds can also increase the synthesis Rapid infusion can cause tachycardia, of glutathione, which can both ameliorate laryngospasm, muscle rigidity and the OP induced oxidative stress and enhance weakness. [49,52] OP detoxification. [8,57] D. Benzodiazepines: Hence, it is suggested to include They are used when the patients are agitated antioxidants in the prescription of the and who develop seizures. Diazepam patients with OP poisoning. appears to counteract some aspects of CNS- derived symptoms, which are not affected MORTALITY: by atropine. [20] The commonest cause of death in acute organophosphorus poisoning was respiratory 2. INTENSIVE CARE MANAGEMENT failure. Singh et al reported cardiac arrest as International Journal of Health Sciences & Research (www.ijhsr.org) 253 Vol.4; Issue: 8; August 2014 cause of death in 10% of cases. Namba  Do not transfer pesticides to other reported that death in untreated cases containers that children may mistake occurred within 24 hours and was delayed for cold drink or sweets container. up to 10 days in treated cases. Complete  Never pour pesticides or household recovery usually occurred in 10 days. chemicals down the drain, into the Mortality rate varied depending on poison toilet or storm water drains, rivers or used, duration after exposure, and dams. atropinisation of all the toxins. In Indian studies mortality rate ranged between 4 to CONCLUSION 38%. This mortality was similar to other Acute organophosphorus poisoning developing countries like Srilanka, and may induce multisystem toxicity leading to [30,56] unlike the west where it was < 1%. severe toxicity and death .Poisoning is diagnosed on the basis of history and Prevention of OP Poisoning [42] clinical examination; biochemical Due to the toxicity of pesticides and the risk investigations can have a role for confirming involved in treatments, there was general the diagnosis.Management consists of agreement that emphasis should be on prompt resuscitation, antidotes as required preventing pesticide illness rather than (particularly atropine, oximes, relying on treatment. benzodiazepines), and selective  Ensure that there was always decontamination .Ongoing monitoring and adequate ventilation when using or high quality supportive care are essential applying pesticides in the home or on Healthcare staff treating exposed patients pets, i.e. keep the doors and windows should exercise standard precautions. open at all times.  Do not use pesticides indoors if they REFERENCES were only designed to be used 1. 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How to cite this article: Yatendra S, Joshi SC, Singh M et. al. Organophosphorus poisoning: an overview. Int J Health Sci Res. 2014;4(8):245-257.

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