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Related Concept Videos

Cholinesterases: Distribution and Function01:22

Cholinesterases: Distribution and Function

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Cholinesterases are a group of serine hydrolase enzymes that play a crucial role in the breakdown of choline esters. The two primary types of cholinesterases are acetylcholinesterases (AChEs) and butyrylcholinesterase (BuChEs), which differ in their distribution, function, and substrate specificity. AChEs, also known as true cholinesterases, specifically hydrolyze acetylcholine, while BuChEs, often referred to as pseudocholinesterases, can hydrolyze various choline esters, including...
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Anticholinesterase Agents: Poisoning and Treatment01:26

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Anticholinesterases, also known as cholinesterase inhibitors, work by blocking the breakdown of acetylcholine, leading to its accumulation in the synaptic cleft. This accumulation indirectly enhances both muscarinic and nicotinic actions. These agents are classified as reversible or irreversible based on their mechanism of action.     
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
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Indirect-Acting Cholinergic Agonists: Pharmacological Actions01:30

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Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
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Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists01:30

Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists

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Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function.
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Indirect-Acting Cholinergic Agonists: Pharmacokinetics01:22

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Indirect-acting cholinergic agonists, or anticholinesterases, enhance the body's cholinergic activity by inhibiting acetylcholine's breakdown. They are categorized as reversible or irreversible agents based on their mechanism of action. They are further classified into short-acting, intermediate-acting, and long-acting agents based on their duration of action.
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Direct-Acting Cholinergic Agonists: Pharmacokinetics01:31

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Direct-acting cholinergic agonists, such as synthetic choline esters and naturally occurring alkaloids, exert their effects by enhancing the actions of acetylcholine and stimulating the parasympathetic nervous system. Synthetic choline esters share structural similarities with acetylcholine. For example, they have a positively charged quaternary ammonium or onium group, contributing to their hydrophilic characteristics. As a result, they are poorly absorbed in the body through oral...
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A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
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Association between cholinesterase activity and critical illness brain dysfunction.

Christopher G Hughes1, Christina S Boncyk2, Benjamin Fedeles3,4

  • 1Department of Anesthesiology, Division of Anesthesiology Critical Care Medicine and Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, 1211 21st Ave. South, 422 MAB, Nashville, TN, 37212, USA. christopher.hughes@vumc.org.

Critical Care (London, England)
|December 6, 2022
PubMed
Summary

Cholinesterase activity in critically ill patients correlates with delirium but not long-term cognitive outcomes. This finding may shed light on acute brain dysfunction mechanisms in the intensive care unit (ICU).

Keywords:
AcetylcholinesteraseButyrylcholinesteraseCognitive impairmentCritical illnessDelirium

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Area of Science:

  • Neuroscience
  • Critical Care Medicine
  • Biochemistry

Background:

  • Delirium is a common complication in critically ill patients, linked to acute brain dysfunction and cognitive impairment.
  • Neuroinflammation, partly regulated by the cholinergic system, is a proposed mechanism for critical illness-related brain dysfunction.
  • Serum cholinesterase enzyme activity offers a real-time measure of cholinergic activity.

Purpose of the Study:

  • To investigate the association between cholinesterase activity and delirium in intensive care unit (ICU) patients.
  • To determine if cholinesterase activity predicts cognitive impairment after hospital discharge.

Main Methods:

  • Adults with respiratory failure and/or shock had plasma acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity measured on days 1, 3, 5, and 7.
  • Mental status (delirium, coma) was assessed daily using the Richmond Agitation Sedation Scale and Confusion Assessment Method for the ICU.
  • Cognitive function, disability, and quality of life were evaluated up to 6 months post-discharge.

Main Results:

  • Higher daily AChE levels were associated with increased odds of delirium on the same day (OR 1.64 [1.11, 2.43], P=0.045).
  • AChE normalized to hemoglobin (AChE/Hgb) and BChE activity were not linked to delirious mental status.
  • Lower BChE at enrollment correlated with fewer days alive without delirium or coma (P=0.048).
  • No significant association was found between cholinesterase levels and post-discharge cognitive impairment, disability, or quality of life.

Conclusions:

  • Cholinesterase activity during critical illness is linked to the presence of delirium.
  • This association appears specific to the acute phase, as cholinesterase levels did not predict long-term cognitive outcomes.
  • These findings contribute to understanding the mechanisms of acute brain dysfunction in critical illness.