Neuroleptic Malignant Syndrome: Mechanisms, Interactions, and Causality
Identifieur interne : 001F30 ( Main/Exploration ); précédent : 001F29; suivant : 001F31Neuroleptic Malignant Syndrome: Mechanisms, Interactions, and Causality
Auteurs : P. Ken Gillman [Australie] ; Mrc Psych [Australie]Source :
- Movement disorders [ 0885-3185 ] ; 2010.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
This review focuses on new data from recent publications concerning how compounding interactions between different thermoregulatory pathways influence the development of hyperthermia and/or neuroleptic malignant syndrome (NMS), and the fundamental issue of the presumed causal role of antipsychotic drugs. The formal criteria for substantiating cause-effect relationships in medical science, established by Hill, are applied to NMS and, for comparison, also to malignant hyperthermia and serotonin toxicity. The risk of morbidities related to hyperthermia is reviewed from human and experimental data: temperatures in excess of 39.5°C cause physiological and cellular dysfunction and high mortality. The most temperature-sensitive elements of neural cells are mitochondrial and plasma membranes, in which irreversible changes occur around 40°C. Temperatures of up to 39°C are "normal" in mammals, so, the term hyperthermia should be reserved for temperatures of 39.5°C or greater. The implicitly accepted presumption that NMS is a hypermetabolic and hyperthermic syndrome is questionable and does not explain the extensive morbidity in the majority of cases, where the temperature is less than 39°C. The thermoregulatory effects of dopamine and acetylcholine are outlined, especially because they are probably the main pathways by which neuroleptic drugs might affect thermoregulation. It is notable that even potent antagonism of these mechanisms rarely causes temperature elevation and that multiple mechanisms, including the acute phase response, stress-induced hyperthermia, drugs effects, etc., involving compounding interactions, are required to precipitate hyperthermia. The application of the Hill criteria clearly supports causality for drugs inducing both MH and ST but do not support causality for NMS.
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Ken Gillman</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Psycho Tropical Research</s1><s2>Queensland</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Psycho Tropical Research</wicri:noRegion></affiliation></author><author><name sortKey="Psych, Mrc" sort="Psych, Mrc" uniqKey="Psych M" first="Mrc" last="Psych">Mrc Psych</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Psycho Tropical Research</s1><s2>Queensland</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Psycho Tropical Research</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">10-0446281</idno><date when="2010">2010</date><idno type="stanalyst">PASCAL 10-0446281 INIST</idno><idno type="RBID">Pascal:10-0446281</idno><idno type="wicri:Area/PascalFrancis/Corpus">000934</idno><idno type="wicri:Area/PascalFrancis/Curation">002385</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000946</idno><idno type="wicri:doubleKey">0885-3185:2010:Ken Gillman P:neuroleptic:malignant:syndrome</idno><idno type="wicri:Area/Main/Merge">002533</idno><idno type="wicri:Area/Main/Curation">001F30</idno><idno type="wicri:Area/Main/Exploration">001F30</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Neuroleptic Malignant Syndrome: Mechanisms, Interactions, and Causality</title><author><name sortKey="Ken Gillman, P" sort="Ken Gillman, P" uniqKey="Ken Gillman P" first="P." last="Ken Gillman">P. Ken Gillman</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Psycho Tropical Research</s1><s2>Queensland</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Psycho Tropical Research</wicri:noRegion></affiliation></author><author><name sortKey="Psych, Mrc" sort="Psych, Mrc" uniqKey="Psych M" first="Mrc" last="Psych">Mrc Psych</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Psycho Tropical Research</s1><s2>Queensland</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Psycho Tropical Research</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Causality</term><term>Induced hyperthermia</term><term>Interaction</term><term>Malignant syndrome</term><term>Morbidity</term><term>Nervous system diseases</term><term>Neuroleptic</term><term>Treatment</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Syndrome malin</term><term>Pathologie du système nerveux</term><term>Interaction</term><term>Causalité</term><term>Neuroleptique</term><term>Traitement</term><term>Hyperthermie provoquée</term><term>Morbidité</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">This review focuses on new data from recent publications concerning how compounding interactions between different thermoregulatory pathways influence the development of hyperthermia and/or neuroleptic malignant syndrome (NMS), and the fundamental issue of the presumed causal role of antipsychotic drugs. The formal criteria for substantiating cause-effect relationships in medical science, established by Hill, are applied to NMS and, for comparison, also to malignant hyperthermia and serotonin toxicity. The risk of morbidities related to hyperthermia is reviewed from human and experimental data: temperatures in excess of 39.5°C cause physiological and cellular dysfunction and high mortality. The most temperature-sensitive elements of neural cells are mitochondrial and plasma membranes, in which irreversible changes occur around 40°C. Temperatures of up to 39°C are "normal" in mammals, so, the term hyperthermia should be reserved for temperatures of 39.5°C or greater. The implicitly accepted presumption that NMS is a hypermetabolic and hyperthermic syndrome is questionable and does not explain the extensive morbidity in the majority of cases, where the temperature is less than 39°C. The thermoregulatory effects of dopamine and acetylcholine are outlined, especially because they are probably the main pathways by which neuroleptic drugs might affect thermoregulation. It is notable that even potent antagonism of these mechanisms rarely causes temperature elevation and that multiple mechanisms, including the acute phase response, stress-induced hyperthermia, drugs effects, etc., involving compounding interactions, are required to precipitate hyperthermia. The application of the Hill criteria clearly supports causality for drugs inducing both MH and ST but do not support causality for NMS.</div></front></TEI><affiliations><list><country><li>Australie</li></country></list><tree><country name="Australie"><noRegion><name sortKey="Ken Gillman, P" sort="Ken Gillman, P" uniqKey="Ken Gillman P" first="P." last="Ken Gillman">P. 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