Medical treatment of acute poisoning with organophosphorus and carbamate pesticides

Academy of Sciences and Arts of Republic Srpska, Banja Luka, Republic Srpska, Bosnia and Herzegovina.
Toxicology Letters (Impact Factor: 3.26). 08/2009; 190(2):107-15. DOI: 10.1016/j.toxlet.2009.07.025
Source: PubMed


Organophosphorus compounds (OPs) are used as pesticides and developed as warfare nerve agents such as tabun, soman, sarin, VX and others. Exposure to even small amounts of an OP can be fatal and death is usually caused by respiratory failure. The mechanism of OP poisoning involves inhibition of acetylcholinesterase (AChE) leading to inactivation of the enzyme which has an important role in neurotransmission. AChE inhibition results in the accumulation of acetylcholine at cholinergic receptor sites, producing continuous stimulation of cholinergic fibers throughout the nervous systems. During more than five decades, pyridinium oximes have been developed as therapeutic agents used in the medical treatment of poisoning with OP. They act by reactivation of AChE inhibited by OP. However, they differ in their activity in poisoning with pesticides and warfare nerve agents and there is still no universal broad-spectrum oxime capable of protecting against all known OP. In spite of enormous efforts devoted to development of new pyridinium oximes as potential antidotes against poisoning with OP only four compounds so far have found its application in human medicine. Presently, a combination of an antimuscarinic agent, e.g. atropine, AChE reactivator such as one of the recommended pyridinium oximes (pralidoxime, trimedoxime, obidoxime and HI-6) and diazepam are used for the treatment of OP poisoning in humans. In this article the available data related to medical treatment of poisoning with OP pesticides are reviewed and the current recommendations are presented.

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    • "Many articles about organophosphate and carbamate intoxication have been published, but data has been limited because it was only a part of intoxication of agricultural chemicals or overall drugs or a part of death statistics [10,11]. Clinical studies have been based on a single hospital or targeted areas [16] and mainly in regards to the treatment in hospital or prognostic factors [17-19]. There also has been a lack of research on the effects of hospitals and departments. "
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    ABSTRACT: This study considered whether there could be a change of mortality and length of stay as a result of inter-hospital transfer, clinical department, and size of hospital for patients with organophosphates and carbamates poisoning via National Patients Sample data of the year 2009, which was obtained from Health Insurance Review and Assessment Services (HIRA). The utility and representativeness of the HIRA data as the source of prognosis analysis in poisoned patients were also evaluated. Organophosphate and carbamate poisoned patients' mortality and length of stay were analyzed in relation to the initial and final treating hospitals and departments, as well as the presence of inter-hospital transfers. Among a total of 146 cases, there were 17 mortality cases, and the mean age was 56.8 ± 19.2 years. The median length of stay was 6 days. There was no inter-hospital or inter-departmental difference in length of stay. However, it significantly increased when inter-hospital transfer occurred (transferred 11 days vs. non-transferred 6 days; p = 0.037). Overall mortality rate was 11.6%. The mortality rate significantly increased when inter-hospital transfer occurred (transferred 23.5% vs. non-transferred 7.0%; p = 0.047), but there was no statistical difference in mortality on inter-hospital and inter-department comparison at the initial treating facility. However, at the final treating facility, there was a significant difference between tertiary and general hospitals (5.1% for tertiary hospitals and 17.3% for general hospitals; p = 0.024), although there was no significant inter-departmental difference. We demonstrated that hospital, clinical department, length of stay, and mortality could be analyzed using insurance claim data of a specific disease group. Our results also indicated that length of stay and mortality according to inter-hospital transfer could be analyzed, which was previously unknown.
    Healthcare Informatics Research 12/2013; 19(4):278-85. DOI:10.4258/hir.2013.19.4.278
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    • "Nerve agents are not easy to detect prior to the appearance of human casualties when misused in chemical warfare or chemical terrorism. Experiences from the Tokyo subway attack point to the necessity of fast countermeasures [9,10]. Detection of the agents is needed for initiation of the provision of suitable prophylactic and therapeutic care. "
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    ABSTRACT: The enzyme acetylcholinesterase (AChE) is an important part of cholinergic nervous system, where it stops neurotransmission by hydrolysis of the neurotransmitter acetylcholine. It is sensitive to inhibition by organophosphate and carbamate insecticides, some Alzheimer disease drugs, secondary metabolites such as aflatoxins and nerve agents used in chemical warfare. When immobilized on a sensor (physico-chemical transducer), it can be used for assay of these inhibitors. In the experiments described herein, an AChE- based electrochemical biosensor using screen printed electrode systems was prepared. The biosensor was used for assay of nerve agents such as sarin, soman, tabun and VX. The limits of detection achieved in a measuring protocol lasting ten minutes were 7.41 × 10-12 mol/L for sarin, 6.31 × 10-12 mol /L for soman, 6.17 × 10-11 mol/L for tabun, and 2.19 × 10-11 mol/L for VX, respectively. The assay was reliable, with minor interferences caused by the organic solvents ethanol, methanol, isopropanol and acetonitrile. Isopropanol was chosen as suitable medium for processing lipophilic samples.
    Sensors 09/2013; 13(9):11498-506. DOI:10.3390/s130911498 · 2.25 Impact Factor
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    • "AChE is a target for many drugs and toxins. Organophosphorus pesticides, carbamate pesticides and nerve agents are examples of toxic compounds inhibiting AChE [6,7]. Huperzine and its derivative, ZT-1, donepezil, galantamine and rivastigmine can be mentioned as drugs for Alzheimer disease inhibiting AChE [8–10]. "
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    ABSTRACT: Caffeine is an alkaloid with a stimulant effect in the body. It can interfere in transmissions based on acetylcholine, epinephrine, norepinephrine, serotonin, dopamine and glutamate. Clinical studies indicate that it can be involved in the slowing of Alzheimer disease pathology and some other effects. The effects are not well understood. In the present work, we focused on the question whether caffeine can inhibit acetylcholinesterase (AChE) and/or, butyrylcholinesterase (BChE), the two enzymes participating in cholinergic neurotransmission. A standard Ellman test with human AChE and BChE was done for altering concentrations of caffeine. The test was supported by an in silico examination as well. Donepezil and tacrine were used as standards. In compliance with Dixon's plot, caffeine was proved to be a non-competitive inhibitor of AChE and BChE. However, inhibition of BChE was quite weak, as the inhibition constant, Ki, was 13.9 ± 7.4 mol/L. Inhibition of AChE was more relevant, as Ki was found to be 175 ± 9 µmol/L. The predicted free energy of binding was -6.7 kcal/mol. The proposed binding orientation of caffeine can interact with Trp86, and it can be stabilize by Tyr337 in comparison to the smaller Ala328 in the case of human BChE; thus, it can explain the lower binding affinity of caffeine for BChE with reference to AChE. The biological relevance of the findings is discussed.
    International Journal of Molecular Sciences 05/2013; 14(5):9873-9882. DOI:10.3390/ijms14059873 · 2.86 Impact Factor
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