Reactivation of Plasma Butyrylcholinesterase by Pralidoxime Chloride in Patients Poisoned by WHO Class II Toxicity Organophosphorus Insecticides
Identifieur interne : 001917 ( Pmc/Checkpoint ); précédent : 001916; suivant : 001918Reactivation of Plasma Butyrylcholinesterase by Pralidoxime Chloride in Patients Poisoned by WHO Class II Toxicity Organophosphorus Insecticides
Auteurs : Lisa A. Konickx ; Franz Worek ; Shaluka Jayamanne ; Horst Thiermann ; Nicholas A. Buckley ; Michael EddlestonSource :
- Toxicological Sciences [ 1096-6080 ] ; 2013.
Abstract
Some clinicians assess the efficacy of pralidoxime in organophosphorus (OP) poisoned patients by measuring reactivation of butyrylcholinesterase (BuChE). However, the degree of BuChE inhibition varies by OP insecticide, and it is unclear how well oximes reactivate BuChE
Url:
DOI: 10.1093/toxsci/kft217
PubMed: 24052565
PubMed Central: 3858199
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Reactivation of Plasma Butyrylcholinesterase by Pralidoxime Chloride in Patients Poisoned by WHO Class II Toxicity Organophosphorus Insecticides</title>
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<author><name sortKey="Eddleston, Michael" sort="Eddleston, Michael" uniqKey="Eddleston M" first="Michael" last="Eddleston">Michael Eddleston</name>
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<series><title level="j">Toxicological Sciences</title>
<idno type="ISSN">1096-6080</idno>
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<front><div type="abstract" xml:lang="en"><p>Some clinicians assess the efficacy of pralidoxime in organophosphorus (OP) poisoned patients by measuring reactivation of butyrylcholinesterase (BuChE). However, the degree of BuChE inhibition varies by OP insecticide, and it is unclear how well oximes reactivate BuChE <italic>in vivo</italic>
. We aimed to assess the usefulness of BuChE activity to monitor pralidoxime treatment by studying its reactivation after pralidoxime administration to patients with laboratory-proven World Health Organization (WHO) class II OP insecticide poisoning. Patient data were derived from 2 studies, a cohort study (using a bolus treatment of 1g pralidoxime chloride) and a randomized controlled trial (RCT) (comparing 2g pralidoxime over 20min, followed by an infusion of 0.5g/h, with placebo). Two grams of pralidoxime variably reactivated BuChE in patients poisoned by 2 diethyl OP insecticides, chlorpyrifos and quinalphos; however, unlike acetylcholinesterase reactivation, this reactivation was not sustained. It did not reactivate BuChE inhibited by the dimethyl OPs dimethoate or fenthion. The 1-g dose produced no reactivation. Pralidoxime produced variable reactivation of BuChE in WHO class II OP-poisoned patients according to the pralidoxime dose administered, OP ingested, and individual patient. The use of BuChE assays for monitoring the effect of pralidoxime treatment is unlikely to be clinically useful.</p>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Toxicol Sci</journal-id>
<journal-id journal-id-type="iso-abbrev">Toxicol. Sci</journal-id>
<journal-id journal-id-type="hwp">toxsci</journal-id>
<journal-id journal-id-type="publisher-id">toxsci</journal-id>
<journal-title-group><journal-title>Toxicological Sciences</journal-title>
</journal-title-group>
<issn pub-type="ppub">1096-6080</issn>
<issn pub-type="epub">1096-0929</issn>
<publisher><publisher-name>Oxford University Press</publisher-name>
<publisher-loc>US</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">24052565</article-id>
<article-id pub-id-type="pmc">3858199</article-id>
<article-id pub-id-type="doi">10.1093/toxsci/kft217</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Reactivation of Plasma Butyrylcholinesterase by Pralidoxime Chloride in Patients Poisoned by WHO Class II Toxicity Organophosphorus Insecticides</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" corresp="no"><name><surname>Konickx</surname>
<given-names>Lisa A.</given-names>
</name>
<xref ref-type="aff" rid="AF0001">*</xref>
<xref ref-type="aff" rid="AF0002">†</xref>
</contrib>
<contrib contrib-type="author" corresp="no"><name><surname>Worek</surname>
<given-names>Franz</given-names>
</name>
<xref ref-type="aff" rid="AF0003">‡</xref>
</contrib>
<contrib contrib-type="author" corresp="no"><name><surname>Jayamanne</surname>
<given-names>Shaluka</given-names>
</name>
<xref ref-type="aff" rid="AF0004">§</xref>
<xref ref-type="aff" rid="AF0005">¶</xref>
</contrib>
<contrib contrib-type="author" corresp="no"><name><surname>Thiermann</surname>
<given-names>Horst</given-names>
</name>
<xref ref-type="aff" rid="AF0003">‡</xref>
</contrib>
<contrib contrib-type="author" corresp="no"><name><surname>Buckley</surname>
<given-names>Nicholas A.</given-names>
</name>
<xref ref-type="aff" rid="AF0006">||</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Eddleston</surname>
<given-names>Michael</given-names>
</name>
<xref ref-type="aff" rid="AF0001">*</xref>
<xref ref-type="aff" rid="AF0005">¶</xref>
<xref ref-type="corresp" rid="c1"><sup>1</sup>
</xref>
</contrib>
<aff id="AF0001">*<institution>Department of Pharmacology, Toxicology, and Therapeutics, University/BHF Centre for Cardiovascular Science, University of Edinburgh</institution>
,<addr-line>Edinburgh, EH16 4TJ</addr-line>
,<country>UK</country>
;</aff>
<aff id="AF0002">†<institution>School of Pharmacy, University of Utrecht</institution>
,<addr-line>3508 TC Utrecht</addr-line>
,<country>The Netherlands</country>
;</aff>
<aff id="AF0003">‡<institution>Bundeswehr Institute of Pharmacology and Toxicology</institution>
,<addr-line>80937 Munich</addr-line>
,<country>Germany</country>
;</aff>
<aff id="AF0004">§<institution>Faculty of Medicine, University of Kelaniya</institution>
,<addr-line>Colombo</addr-line>
,<country>Sri Lanka</country>
;</aff>
<aff id="AF0005">¶<institution>South Asian Clinical Toxicology Research Collaboration, University of Peradeniya</institution>
,<country>Sri Lanka</country>
; and</aff>
<aff id="AF0006">||<institution>Medical Professorial Unit, Prince of Wales Hospital Clinical School, University of New South Wales</institution>
,<addr-line>Sydney, NSW 2052</addr-line>
,<country>Australia</country>
</aff>
</contrib-group>
<author-notes><corresp id="c1"><sup>1</sup>
To whom correspondence should be addressed at Department of Pharmacology, Toxicology, and Therapeutics, QMRI E3.20, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. Fax: <fax>131 242 9215</fax>
. E-mail: <email>m.eddleston@ed.ac.uk</email>
.</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>12</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epub"><day>19</day>
<month>9</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>19</day>
<month>9</month>
<year>2013</year>
</pub-date>
<volume>136</volume>
<issue>2</issue>
<fpage>274</fpage>
<lpage>283</lpage>
<history><date date-type="received"><day>23</day>
<month>5</month>
<year>2013</year>
</date>
<date date-type="accepted"><day>10</day>
<month>9</month>
<year>2013</year>
</date>
</history>
<permissions><copyright-statement>© The Author 2013. Published by Oxford University Press on behalf of the Society of Toxicology.</copyright-statement>
<copyright-year>2013</copyright-year>
<license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by/3.0"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/3.0/">http://creativecommons.org/licenses/by/3.0/</ext-link>
), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract><p>Some clinicians assess the efficacy of pralidoxime in organophosphorus (OP) poisoned patients by measuring reactivation of butyrylcholinesterase (BuChE). However, the degree of BuChE inhibition varies by OP insecticide, and it is unclear how well oximes reactivate BuChE <italic>in vivo</italic>
. We aimed to assess the usefulness of BuChE activity to monitor pralidoxime treatment by studying its reactivation after pralidoxime administration to patients with laboratory-proven World Health Organization (WHO) class II OP insecticide poisoning. Patient data were derived from 2 studies, a cohort study (using a bolus treatment of 1g pralidoxime chloride) and a randomized controlled trial (RCT) (comparing 2g pralidoxime over 20min, followed by an infusion of 0.5g/h, with placebo). Two grams of pralidoxime variably reactivated BuChE in patients poisoned by 2 diethyl OP insecticides, chlorpyrifos and quinalphos; however, unlike acetylcholinesterase reactivation, this reactivation was not sustained. It did not reactivate BuChE inhibited by the dimethyl OPs dimethoate or fenthion. The 1-g dose produced no reactivation. Pralidoxime produced variable reactivation of BuChE in WHO class II OP-poisoned patients according to the pralidoxime dose administered, OP ingested, and individual patient. The use of BuChE assays for monitoring the effect of pralidoxime treatment is unlikely to be clinically useful.</p>
</abstract>
<kwd-group><title>Key Words:</title>
<kwd>organophosphorus insecticides</kwd>
<kwd>butyrylcholinest erase</kwd>
<kwd>pralidoxime</kwd>
<kwd>marker</kwd>
<kwd>human poisoning.</kwd>
</kwd-group>
<counts><page-count count="10"></page-count>
</counts>
</article-meta>
</front>
</pmc>
<affiliations><list></list>
<tree><noCountry><name sortKey="Buckley, Nicholas A" sort="Buckley, Nicholas A" uniqKey="Buckley N" first="Nicholas A." last="Buckley">Nicholas A. Buckley</name>
<name sortKey="Eddleston, Michael" sort="Eddleston, Michael" uniqKey="Eddleston M" first="Michael" last="Eddleston">Michael Eddleston</name>
<name sortKey="Jayamanne, Shaluka" sort="Jayamanne, Shaluka" uniqKey="Jayamanne S" first="Shaluka" last="Jayamanne">Shaluka Jayamanne</name>
<name sortKey="Konickx, Lisa A" sort="Konickx, Lisa A" uniqKey="Konickx L" first="Lisa A." last="Konickx">Lisa A. Konickx</name>
<name sortKey="Thiermann, Horst" sort="Thiermann, Horst" uniqKey="Thiermann H" first="Horst" last="Thiermann">Horst Thiermann</name>
<name sortKey="Worek, Franz" sort="Worek, Franz" uniqKey="Worek F" first="Franz" last="Worek">Franz Worek</name>
</noCountry>
</tree>
</affiliations>
</record>
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