<abstract xmlns="http://www.w3.org/1999/xhtml"><p>Respiratory failure is the predominant cause of death in humans and animals poisoned with anticholinesterases. Organophosphorus and carbamate anticholinesterases inhibit acetylcholinesterase irreversibly and reversibly, respectively. Some of them contain a quaternary atom that makes them lipophobic, limiting their action at the periphery, i.e. outside the central nervous system. They impair respiratory function primarily by inducing a desensitization block of nicotinic receptors in the neuromuscular synapse. Lipophilic anticholinesterases inhibit the acetylcholinesterase both in the brain and in other tissues, including respiratory muscles. Their doses needed for cessation of central respiratory drive are significantly less than doses needed for paralysis of the neuromuscular transmission. Antagonist of muscarinic receptors atropine blocks both the central and peripheral muscarinic receptors and effectively antagonizes the central respiratory depression produced by anticholinesterases. To manage the peripheral nicotinic receptor hyperstimulation phenomena, oximes as acetylcholinesterase reactivators are used. Addition of diazepam is useful for treatment of seizures, since they are cholinergic only in their initial phase and can contribute to the occurrence of central respiratory depression. Possible involvement of central nicotinic receptors as well as the other neurotransmitter systems – glutamatergic, opioidergic – necessitates further research of additional antidotes.</p></abstract>

Respiratory failure is the predominant cause of death in humans and animals poisoned with anticholinesterases. Organophosphorus and carbamate anticholinesterases inhibit acetylcholinesterase irreversibly and reversibly, respectively. Some of them contain a quaternary atom that makes them lipophobic, limiting their action at the periphery, i.e. outside the central nervous system. They impair respiratory function primarily by inducing a desensitization block of nicotinic receptors in the neuromuscular synapse. Lipophilic anticholinesterases inhibit the acetylcholinesterase both in the brain and in other tissues, including respiratory muscles. Their doses needed for cessation of central respiratory drive are significantly less than doses needed for paralysis of the neuromuscular transmission. Antagonist of muscarinic receptors atropine blocks both the central and peripheral muscarinic receptors and effectively antagonizes the central respiratory depression produced by anticholinesterases. To manage the peripheral nicotinic receptor hyperstimulation phenomena, oximes as acetylcholinesterase reactivators are used. Addition of diazepam is useful for treatment of seizures, since they are cholinergic only in their initial phase and can contribute to the occurrence of central respiratory depression. Possible involvement of central nicotinic receptors as well as the other neurotransmitter systems – glutamatergic, opioidergic – necessitates further research of additional antidotes.

Mechanism and Clinical Importance of Respiratory Failure Induced by Anticholinesterases

Department of Internal Medicine, Faculty of Medical Sciences

Department of Anatomy and Forensic Medicine, Faculty of Medical Sciences

Neurology Clinic, University Clinical Centre of Republic of Srpska, Medical Faculty

Institute for Physical Medicine and Rehabilitation „Dr Miroslav Zotovic“

Department of Pharmacology, Toxicology & Clinical Pharmacology, Medical Faculty

Experimental and Applied Biomedical Research (EABR)

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Respiratory failure is the predominant cause of death in humans and animals poisoned with anticholinesterases. Organophosphorus and carbamate...

Mechanism and Clinical Importance of Respiratory Failure Induced by Anticholinesterases

Publié en ligne: 29 déc. 2017

Pages: 349 - 355

Reçu: 24 mai 2016

Accepté: 14 juin 2016

DOI: https://doi.org/10.1515/sjecr-2016-0047

Mots clés
Anticholinesterase, Acetylcholinesterase, Acetylcholine, Atropine, Oxime, Diazepam, Respiratory depression, Muscarinic receptors, Nicotinic receptors

© 2017 Anita Ivosevic et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Mechanism and Clinical Importance of Respiratory Failure Induced by Anticholinesterases

Publié en ligne: 29 déc. 2017

Pages: 349 - 355

Reçu: 24 mai 2016

Accepté: 14 juin 2016

DOI: https://doi.org/10.1515/sjecr-2016-0047

Mots clésAnticholinesterase, Acetylcholinesterase, Acetylcholine, Atropine, Oxime, Diazepam, Respiratory depression, Muscarinic receptors, Nicotinic receptors

© 2017 Anita Ivosevic et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Mots clés
Anticholinesterase, Acetylcholinesterase, Acetylcholine, Atropine, Oxime, Diazepam, Respiratory depression, Muscarinic receptors, Nicotinic receptors