Acetylcholine clinical effects

Local anesthetics have poorly understood effects on inflammation at sites of injury, and these anti-inflammatory effects may contribute to improved pain control in some chronic pain syndromes. At the concentrations used in spinal anesthesia, local anesthetics can inhibit transmission via substance P (neurokinin-1), NMDA, and AMPA receptors in the secondary afferent neurons (Figure 26-1). These effects may contribute to the analgesia achieved by subarachnoid administration. Local anesthetics can also be shown to block a variety of other ion channels, including nicotinic acetylcholine channels in the spinal cord. However, there is no convincing evidence that this mechanism is important in the acute clinical effects of these drugs. High concentrations of local anesthetics in the subarachnoid space can interfere with intra-axonal transport and calcium homeostasis, contributing to potential spinal toxicity. 

Following nerve agent exposure, inhibition of the tissue enzyme blocks its ability to hydrolyze the neurotransmitter acetylcholine at the cholinergic receptor sites. Thus, acetylcholine accumulates and continues to stimulate the affected organ. The clinical effects of nerve agent exposure are caused by excess acetylcholine. 

The clinical effects of nerve agents are, to a large extent, those of acetylcholine accumulation and the effects of all of the nerve agents are similar. Those differences that have been observed are presumably due to a combination of different rates of inactivation and reactivation of the enzymes, together with different rates of ageing of the inhibited enzyme and differences in absorption, distribution, metabolism and... 

The toxic effects of nerve agents are due primarily to their inhibition of acetylcholinesterase and the resulting accumulation of acetylcholine.8 Other biological activities of these agents have been described, but the relation of these activities to clinical effects has not been recognized. For example, some nerve agents affect ionic channels,9 and all... 

The empiric dose for suspected botulism is one to two vials. Guanidine increases the release of acetylcholine at the nerve terminal, but has not been shown to be clinically effective. 

This makes choline an important nutritional substance. It is also of great physiological interest because one of its esters, acetylcholine [51-84-3] appears to be responsible for the mediation of parasympathetic nerve impulses and has been postulated to be essential to the transmission of all nerve impulses. Acetylcholine and other more stable compounds that simulate its action are pharmacologically important because of their powerful effect on the heart and on smooth muscle. Choline is used clinically in Hver disorders and as a constituent in animal feeds. 

Organophosphate Ester Hydraulic Fluids. The biomarkers of effects after exposure to organophosphate ester hydraulic fluids are well established in cases of delayed neuropathy (clinical signs of peripheral neuropathy). Further study would be helpful to determine whether certain effects (such as diarrhea after oral exposure) are due to direct action of the toxic agent on the target organ or to inhibition of acetylcholinesterase at the acetylcholine nerve receptor site on the organ. 

Unlike the muscarinic receptors, repeated exposure of the neuronal receptors to nicotine, both in vivo and in vitro, results in an increase in the number of receptors similar changes are reported to occur after physostigmine is administered directly into the cerebral ventricles of rats. These changes in the density of the nicotinic receptors are accompanied by an increased release of acetylcholine. Following the chronic administration of physostigmine, however, a desensitization of the receptors occurs. Functionally nicotinic receptors appear to be involved in memory formation in clinical studies it has been shown that nicotine can reverse the effects of scopolamine on short-term working memory and both... 

Irreversible anticholinesterases include the organophosphorus inhibitors and ambenonium, which irreversibly phosphorylate the esteratic site. Such drugs have few clinical uses but have been developed as insecticides and nerve gases. Besides blocking the muscarinic receptors with atropine sulphate in an attempt to reduce the toxic effects that result from an accumulation of acetylcholine, the only specific treatment for organopho-sphate poisoning would appear to be the administration of 2-pyridine aldoxime methiodide, which increases the rate of dissociation of the organophosphate from the esteratic site on the enzyme surface. 

Citicoline (cytidinediphosphate-choline/CDP-choline 26) is an intermediate in the biosynthesis of acetylcholine. It has been extensively used for the treatment of neurodegenerative disorders associated with head trauma, stroke, brain aging, and AD. Studies in mice have indicated a protective effect of citicohne against memory impairment induced by adverse environments. A human study recruited 30 patients with mild to moderate AD in a double-blind, randomized and placebo-controlled clinical trial... 

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