scholarly journals Mechanism and Clinical Importance of Respiratory Failure Induced by Anticholinesterases

2017 ◽  
Vol 18 (4) ◽  
pp. 349-355
Author(s):  
Anita Ivosevic ◽  
Natasa Miletic ◽  
Maja Vulovic ◽  
Zoran Vujkovic ◽  
Snjezana Novakovic Bursac ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Respiratory Depression ◽  
Muscarinic Receptors ◽  
Nicotinic Receptors ◽  
Neuromuscular Synapse ◽  
Clinical Importance ◽  
Respiratory Muscles ◽  
Respiratory Drive ◽  
The Central Nervous System ◽  
Central Nicotinic Receptors

AbstractRespiratory 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.

Effect of agonists and antagonists of cholinergic neurotransmission on growth hormone release in the dog

1983 ◽  
Vol 103 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Felipe F. Casanueva ◽  
Roberto Betti ◽  
Silvano G. Cella ◽  
Eugenio E. Müller ◽  
Paolo Mantegazza
Keyword(s):  
Growth Hormone ◽  
Muscarinic Receptors ◽  
Nicotinic Receptors ◽  
Anticholinergic Drug ◽  
Complete Suppression ◽  
Butyl Bromide ◽  
Clear Cut ◽  
The Central Nervous System ◽  
Pre Treatment ◽  
Releasing Effect

Abstract. In unanaesthetized dogs iv administration of the cholinesterase inhibitor eserine (0.5 mg) or the cholinergic muscarinic receptor agonist oxotremorine (0.25 mg) induced a clear-cut rise in plasma canine growth hormone (cGH) levels. Complete suppression of the GH-releasing effect of eserine and oxotremorine was induced by blockade of cholinergic muscarinic receptors by atropine (80 or 20 μg/kg, 30 min before) but not by scopolamine-N-butyl bromide (0.8 mg/dog, 30 min before), an anticholinergic drug which does not cross the blood brain barrier (BBB). In contrast, activation of cholinergic nicotinic receptors by nicotine (6 mg) failed to alter resting cGH concentrations, and pre-treatment with the nicotinic receptor blocker mecamylamine (5 mg, 30 min before) did not counteract the GH-releasing effect of eserine. Other cholinomimetic drugs, e.g. pilocarpine, 4-aminopyridine, carbachol and bethanechol failed to induce a rise in plasma cGH concentrations. These data indicate that: 1) cholinergic muscarinic but not nicotinic receptors located in the central nervous system (CNS) inside the BBB play a facilitatory role in tonic cGH release; 2) pharmacologically distinct muscarinic receptors may exist in the CNS.

N-acetylcysteine administration alters the response to inspiratory loading in oxygen-supplemented rats

1997 ◽  
Vol 82 (4) ◽  
pp. 1119-1125 ◽  
Author(s):  
G. S. Supinski ◽  
D. Stofan ◽  
R. Ciufo ◽  
A. Dimarco
Keyword(s):  
Free Radical ◽  
Respiratory Failure ◽  
Respiratory Muscles ◽  
Treated Group ◽  
Respiratory Arrest ◽  
Saline Group ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Resistive Load ◽  
Loaded Breathing

Supinski, G. S., D. Stofan, R. Ciufo, and A. DiMarco. N-acetylcysteine administration alters the response to inspiratory loading in oxygen-supplemented rats. J. Appl. Physiol. 82(4): 1119–1125, 1997.—Based on recent studies, it has been suggested that free radicals are elaborated in the respiratory muscles during strenuous contractions and contribute to the development of muscle fatigue. If this theory is correct, then it should be possible to attenuate the development of diaphragm fatigue and/or delay the onset of respiratory failure during loaded breathing by administering a free radical scavenger. The purpose of the present experiment was, therefore, to examine the effect of N-acetylcysteine (NAC), a free radical scavenger and glutathione precursor, on the evolution of respiratory failure in decerebrate unanesthetized rats breathing against a large inspiratory resistive load. We compared the inspiratory volume and pressure generation over time in animals pretreated with either saline or NAC (150 mg/kg) and then loaded until respiratory arrest. After arrest, the diaphragm was excised, and samples were assayed for reduced (GSH) and oxidized glutathione. As a control, we also assessed respiratory function and glutathione concentrations in groups of nonloaded saline- and NAC-treated animals. We found that NAC-treated animals were able to tolerate loading better than the saline-treated group, maintaining higher inspiratory pressures and sustaining higher inspired volumes. Administration of NAC also increased the time that animals could tolerate loading before the development of respiratory arrest. In addition, although saline-treated loaded animals had significant reductions in diaphragmatic GSH levels compared with unloaded controls, the magnitude of this reduction was blunted by NAC administration (i.e., GSH averaged 965 ± 113, 568 ± 83, 907 ± 39, and 784 ± 61 nmol/g for unloaded-saline, loaded-saline, unloaded-NAC, and loaded-NAC groups, P< 0.05, with the value for the loaded-saline group lower than the values for the two unloaded groups; GSH for the loaded-NAC group was not different, however, from unloaded controls). These data demonstrate that administration of NAC, a free radical scavenger, slows the rate of development of respiratory failure during inspiratory resistive loading.

Characterization of Central Nicotinic Receptors

1987 ◽  
Vol 505 (1 Myasthenia Gr) ◽  
pp. 764-766 ◽  
Author(s):  
C. GOTTI ◽  
D. FORNASARI ◽  
M. BOZZI ◽  
F. CLEMENTI
Keyword(s):  
Nicotinic Receptors ◽  
Central Nicotinic Receptors

scholarly journals Fatal Nemaline Myopathy in Infancy

1984 ◽  
Vol 11 (2) ◽  
pp. 305-309 ◽  
Author(s):  
Joseph B. McMenamin ◽  
Bernadette Curry ◽  
Glen P. Taylor ◽  
Laurence E. Becker ◽  
E. Gordon Murphy
Keyword(s):  
Respiratory Failure ◽  
Peripheral Nerves ◽  
Neonatal Period ◽  
Nemaline Myopathy ◽  
Clinical Findings ◽  
Neural Basis ◽  
Limb Muscles ◽  
The Central Nervous System ◽  
Severe Hypotonia ◽  
Clinical Stability

ABSTRACT:The clinical and neuropathological findings in two infants with congenital nemaline myopathy are described. One patient presented at birth with severe hypotonia, respiratory failure and contractures and died shortly after the neonatal period. The other presented at age two months with hypotonia and, following a period of clinical stability, died at age seven months from respiratory failure. Pathological findings in the fatal neonatal case revealed numerous rod bodies in lingual, pharyngeal, diaphragm and limb muscles, correlating with clinical findings. Significant, but less rod body involvement was found in the diaphragm and limb muscles of the second patient. Although a neural basis has been suggested for this disorder, no abnormalities were found in the central nervous system or in the peripheral nerves of these two severely affected patients.

Cardiac nicotinic receptors show β-subunit dependent compensatory changes

2021 ◽  
Author(s):  
Katarina Targosova ◽  
Matej Kucera ◽  
Zuzana Kilianova ◽  
Lubica Slobodova ◽  
Kristina Szmicsekova ◽  
...  
Keyword(s):  
Heart Rate ◽  
Muscarinic Receptors ◽  
Nicotinic Receptors ◽  
Isolated Heart ◽  
High Dose ◽  
Β Subunit ◽  
Adrenergic Stimulation ◽  
Relative Expression ◽  
Isolated Hearts ◽  
Heart Functions

Nicotinic receptors (NR) play an important role in the cholinergic regulation of heart functions, and converging evidence suggests a diverse repertoire of NR subunits in the heart. A recent hypothesis about the plasticity of β NR subunits suggests that β2 and β4 subunits may substitute for each other. In our study, we assessed the hypothetical β subunit interchangeability in the heart at the level of mRNA. Using two mutant mice strains lacking β2 or β4 NR subunits, we examined the relative expression of NR subunits and other key cholinergic molecules. We investigated the physiology of isolated hearts perfused by Langendorff's method at basal conditions and after cholinergic and/or adrenergic stimulation. Lack of β2 NR subunit was accompanied with decreased relative expression of β4 and α3 subunits. No other cholinergic changes were observed at the level of mRNA, except for increased M3 and decreased M4 muscarinic receptors. Isolated hearts lacking β2 NR subunit showed different dynamics in heart rate response to indirect cholinergic stimulation. In hearts lacking β4 NR subunit, increased levels of β2 subunits were observed together with decreased mRNA for acetylcholine-synthetizing enzyme and M1 and M4 muscarinic receptors. Changes in the expression levels in β4-/- hearts were associated with increased basal heart rate and impaired response to a high dose of acetylcholine upon adrenergic stimulation. In support of the proposed plasticity of cardiac NRs, our results confirmed subunit-dependent compensatory changes to missing cardiac NRs subunits with consequences on isolated heart physiology.

scholarly journals Intravenous Sedation in Arnold-Chiari Malformation With Respiratory Failure

2019 ◽  
Vol 66 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Yoshiki Shionoya ◽  
Eishi Nakamura ◽  
Takahiro Goi ◽  
Kiminari Nakamura ◽  
Katsuhisa Sunada
Keyword(s):  
Respiratory Failure ◽  
Respiratory Depression ◽  
Chiari Malformation ◽  
Dental Treatment ◽  
Anesthetic Management ◽  
Cranial Nerves ◽  
Intravenous Sedation ◽  
Type Ii ◽  
Neck Extension ◽  
Arnold Chiari Malformation

Type II Arnold-Chiari malformation (ACM) is an abnormality in which the cerebellum, pons, and medulla oblongata are displaced downward into the spinal cord. Type II ACM is often complicated by respiratory depression, sleep-disordered breathing, and deglutition disorder as a result of medullary dysfunction and impairment of the lower cranial nerves. Bending and stretching of the neck is restricted, and anesthetic management is problematic in patients with the disorder. We performed dental treatment twice under intravenous sedation in a patient with intellectual disability with type II ACM complicated by hypercapnic respiratory failure. Propofol was used for the first sedation procedure. Repeated bouts of respiratory depression occurred on that occasion, so the airway was managed manually by lifting the jaw. However, aspiration pneumonitis occurred postoperatively. A combination of dexmedetomidine and midazolam was used for sedation on the second occasion, and the intervention was completed uneventfully without any respiratory depression. Our experience with this patient highlights the need for selection of an agent for intravenous sedation that does not require neck extension and has minimal effect on respiration in patients with type II ACM, who are at high risk of respiratory depression and pulmonary aspiration.

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