Neuromuscular conduction

The mechanism of diethyxime therapeutic action on the neuromuscular conduction in poisonings with anti-cholinesterase... 

Paralysis of the respiratory musculature develops as a result of impairing neuromuscular conduction and is mainly observed with the exposure to high doses of OPC. At that, along with the anti-cholinesterase mechanism of blockade development, direct influence of chemicals on CR plays a significant role as well as a rise in sensitivity of the transversal striated muscles to ACh. 

Advantages of alloxime over ChR, such as dipiroxime and isonitrosine, consist in more pronounced antidotic-and-therapeutic power at the expense of its ability to penetrate the hematoencephalic barrier and restore activity of cerebral ChE. In addition, it reactivates well activity of blood ChE. The central effect of alloxime is characterized by fast restoration of patients consciousness and improvement in bioelectrical cerebral activity. Its peripheral effects consist in restoration of neuromuscular conduction, normalization of cytochrome P-450 content in the liver and kidneys. Alloxime, similarly to all quaternary oximes of the first generation, is a sufficiently toxic compound. DL50 for the intravenous administration to rats and cats amounts to 135 mg/kg and 126 mg/kg, respectively. 

In conclusion, the following summarizes possible correlative biological markers of early carbon disulfide poisoning (1) electromyographical indications of neural lesions (2) decreased neuromuscular conduction... 

A further enzyme of practical interest is cholinesterase. Cholinesterase, normally involved in the prtx ess of neuromuscular conduction, incidentally hydrolyses succinylcholine, a muscle-relaxing drug used in anaesthesia. Patients with abnormal cholinesterase may fail to hydrolyze the drug normally and as a result suffer prolonged paralysis after anaesthesia. This is called scoline apnoea. Cholinesterase measurements are afso useful in thediagnosisof poisoning with pesticides which are cholinesterase inhibitors. 

Magnesium Decreases uterine contraction. Decreases neuromuscular conduction, X acetylcholine release, vasodilation, respiratory depression at high doses. Premature onset of labor, preeclampsia, eclampsia. ... 

Fig. 5-1. Diagram of neuromuscular conduction, (a) Nerve fiber with axon terminal in synaptic trough of muscle. (b) Close-up of axon terminal in trough, with synaptic vesicles indicated. (c) Acetylcholine synthesis from acetate and choline and storage of acetylcholine in synaptic vesicles, (d) Release of acetylcholine from synaptic vesicles after an action potential. (e) Acetylcholine stimulation of endplate at receptor for site, (f) Hydrolysis of acetylcholine by membrane-bound acetylcholinesterase. Reprinted with permission from Clinical Symposia. 1(1, 8) 162, Plate 3118. West Caldwell, NJ CIBA GEIGY Medical Education Division.

Axonal Injury Myelin injury Neuromuscular conduction defect Myopathy... 

Examples of injuries and deficits axonal injury, critical illness myopathy myelin injury, Guillain-Barre neuromuscular conduction defect, myasthenia, prolonged neuromuscular blockade myopathy, critical illness myopathy. 

R = / -C H ), in low doses, exhibits the former behavior and is used primarily as an extradural agent in obstetrics. The lowest effective extradural concentration of etidocaine (21, X = CH, R = R = 2H, R = / -C H ), however, shows both adequate sensory and profound motor blockade so that it is useful in surgical situations where maximum neuromuscular blockade is necessary. In an isolated nerve preparation, bupivacaine blocks unmyelinated C fibers which are mainly responsible for pain perception at a much greater extent than the myelinated A fibers which carry motor impulses. It is postulated that absorption of bupivacaine by the vasculature at the site of injection, combined with the slow diffusion of this agent, results in an insufficient amount of the drug penetrating the large A fibers to cause motor conduction blockade. Clinically, motor block can be observed in some procedures. 

Goodgold J, Eberstein A. 1983. Motor and sensory nerve conduction measurements. In Electrodiagnosis of neuromuscular diseases. 3rd ed. Baltimore, MD Williams and Wilkins, 104-153. 

Baclofen appears to affect the neuromuscular axis by acting directly on sensory afferents, y-motor neurons, and collateral neurons in the spinal cord to inhibit both monosynaptic and polysynaptic reflexes. The principal effect is to reduce the release of excitatory neurotransmitters by activation of presynaptic GABAg receptors. This seems to involve a G protein and second-messenger link that either increases K+ conductance or decreases Ca conductance. 

A 45-year-old man in otherwise good health complains of muscle weakness early in the morning but says it is less of a problem as the day goes on. The neurologist performs electromyography and notes no alteration in nerve conduction velocity but does observe facilitation in the compound action potential with repetitive 50-Hz stimulation. This indicates a defect at the prejunctional side of the neuromuscular junction. Which of the following is a possible cause ... 

Holmes and Robins reported that 2-PAM I overcame neuromuscular blockade induced by DFP, TEPP, or sarin, but this could be demonstrated with the Isolated phrenic nerve-diaphragm preparation from the rat only after washing away excess OP compound. Intravenous injection of 2-PAM I overcame slowly neuromuscular blockade induced by OP compounds. The oxime, they found, also had a direct toxic action on muscle, reducing the ability of muscle to shorten and decreasing the ability of muscle fibers to conduct impulses. The same investigators reported that V (intraperltoneally at 150 mg/kg) had little, if any, effect on a sarin-induced blockade of neuromuscular transmission. 

Carbamazepine overdose first leads to neuromuscular disturbances, such as nystagmus, myoclonus, and hyperreflexia, with later progression to seizures and coma. Cardiac conduction changes are possible. Nausea, vomiting, and urinary retention also may occur. Treatment should include induction of vomiting, gastric lavage, and supportive care. After a serious overdose, blood pressure and respiratory and kidney function should be monitored for several days. 

The generation of action potentials by muscle and nerve results from changes in the conductance of their membranes to sodium and potassium, and normal neuromuscular function depends on the maintenance of the correct ratio between intracellular and extracellular ionic concentrations. 

Mild hypothermia has been easily incorporated into the overall care of patients in various clinical settings. However, there is a potential for multisystem complications when it is used. Although mild hypothermia (32-34°C) is not usually responsible for cardiac dysrhythmias, it has been associated with electrical conduction disturbances secondary to its potentiation of other drugs, particularly neuromuscular blocking agents (4,45,46). There is a tendency to develop atrial fibrillation at temperatures below 32°C (47). During periods of mild hypothermia,... 

Discussion of vulnerability of the axon and its terminal to toxicants must be based on an appreciation of specialized aspects of the metabolism of the neuron. This cell type has been discussed in the chapter dealing with the CNS. The concepts of chemically mediated neurotransmission, second messenger systems, specialized ion channels, and conduction of waves of depolarization with consequent high demand for energy to restore Na+ and K+ ion gradients are applicable to the PNS as well as the CNS. Of particular relevance is the fact that the neuromuscular junction is cholin-... 

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