How general anesthetics work: from the perspective of reorganized connections within the brain

Shin, Teo Jeon; Kim, Pil-Jong; Choi, Bernard

doi:10.4097/kja.22078

Cited by 4 publications

(3 citation statements)

References 114 publications

(227 reference statements)

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“…The primary inhibitory neurotransmitter in the brain and spinal cord is GABA. Anxiolytic effects at low doses and sedative/hypnotic effects at high dosages are the result of the dosage-dependent action of BZDs on GABA receptors [ 9 ]. There is no specific organ that is required for its rapid metabolism and high clearance rate.…”

Section: Reviewmentioning

confidence: 99%

The Rise of Remimazolam: A Review of Pharmacology, Clinical Efficacy, and Safety Profiles

Dessai,

Ninave,

Bele

2024

Cureus

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Anesthesiologists often use benzodiazepines (BZDs) due to their remarkable amnestic and anxiolytic capabilities. Because of this, they are perfect for use during the perioperative phase, when patients' anxiety levels are already high. Remimazolam has replaced certain commonly used intravenous (IV) anesthetics due to its excellent safety profile, rapid onset of action, and short half-life. The four classes of BZDs, 2-keto-benzodiazepines, 3-hydroxy-benzodiazepines, triazolobenzodiazepines, and 7-nitro-benzodiazepines based on chemical structure, provide various levels of drowsiness, forgetfulness, and anxiolysis. Based on their elimination half-life, short-acting BZDs typically have a half-life ranging from one to 12 hours, e.g., oxazepam; intermediate-acting BZDs have an average elimination half-life of 12 to 40 hours, e.g., alprazolam; and long-acting BZDs have an average elimination half-life of more than 40 hours, e.g., diazepam. The chloride ion channel is conformationally shifted by the benzodiazepine molecule resulting in central nervous system (CNS) inhibition and hyperpolarization. Each type of benzodiazepine has a favored use. For example, diazepam is used to treat anxiety. Midazolam is used for its anxiolytic and anterograde amnestic effects during the perioperative phase. Anxiety and epilepsy are two conditions that lorazepam effectively treats. There are now phase II and III clinical studies investigating remimazolam. It is not sensitive to alterations in its surroundings and has a brief half-life so that it may be removed rapidly, even after extensive infusion. Being a soft drug means the body easily breaks it down via metabolism, which explains many features. Remimazolam is hydrolyzed into methanol and its carboxylic acid metabolite CNS 7054 by esterase metabolism. Therefore, remimazolam has a shorter onset time and faster recovery than other BZDs. Remimazolam is metabolized independently of any particular organ. Patients with hepatic and renal problems will not see any changes in metabolism or excretion since the drug's ester moiety makes it a substrate for general tissue esterase enzymes. Like its predecessor, midazolam, it has a high potential for addiction. Some side effects that could occur during infusion include headaches and drowsiness. In clinical trials, hypotension, respiratory depression, and bradycardia were noted in participants. BZDs are helpful when used in conjunction with anesthesia. Remimazolam stands out, thanks to its unique pharmacokinetics, pharmacodynamics, safety profile, and potential medical applications. Its desirable properties make it a potential surgical premedication and sedative in the critical care unit. Anesthesiologists and other doctors could have access to more consistent and safer medication. However, additional comprehensive clinical trials are necessary to understand remimazolam's advantages and disadvantages.

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Section: Reviewmentioning

confidence: 99%

The Rise of Remimazolam: A Review of Pharmacology, Clinical Efficacy, and Safety Profiles

Dessai,

Ninave,

Bele

2024

Cureus

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“…While the introduction of general anesthesia was a revolutionary achievement in medical history, the mechanism of action of anesthetic agents is still not fully understood. The concept that anesthetic agents produce neuro-depression in specific areas of the central nervous system by enhancing the effect of inhibitory neurotransmitters (especially GABA), reducing the effect of excitatory neurotransmitters, and suppressing specific neuronal network activity necessary for consciousness and arousal has been generally accepted [ 1 , 2 ]. The GABA receptor system is the main inhibitory receptor population in the human central nervous system and the main target receptor for intravenous anesthetic agents that induce general anesthesia [ 1 ].…”

Section: Basic Knowledge On Intravenous Anesthetic Agentsmentioning

confidence: 99%

“…The concept that anesthetic agents produce neuro-depression in specific areas of the central nervous system by enhancing the effect of inhibitory neurotransmitters (especially GABA), reducing the effect of excitatory neurotransmitters, and suppressing specific neuronal network activity necessary for consciousness and arousal has been generally accepted [ 1 , 2 ]. The GABA receptor system is the main inhibitory receptor population in the human central nervous system and the main target receptor for intravenous anesthetic agents that induce general anesthesia [ 1 ]. Most intravenous anesthetic agents, such as barbiturates, BZDs, propofol, and etomidate, bind to GABA type A receptors, except for ketamine, which mainly acts via the N-methyl-D-aspartate (NMDA) receptor along with other receptor types.…”

Section: Basic Knowledge On Intravenous Anesthetic Agentsmentioning

confidence: 99%

Remimazolam – current knowledge on a new intravenous benzodiazepine anesthetic agent

Kim

Fechner

2022

Korean J Anesthesiol

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Intravenous anesthetic agents such as midazolam, propofol, and ketamine are routinely used to provide anesthesia and sedation. They have been shown to effectively induce and maintain amnesia, sedation, and hypnosis in various patient groups and clinical settings. However, all anesthetic agents have the potential to cause unwanted side effects such as hemodynamic instability, respiratory depression, or slow recovery due to prolonged post-procedural sedation. Remimazolam, a recently approved benzodiazepine for general anesthesia and procedural sedation in Korea, has been successfully used for these purposes. To date, inconclusive knowledge has been obtained regarding the use of remimazolam in different patient populations and under various surgical conditions. With respect to the specific pharmacokinetic and pharmacodynamic characteristics of remimazolam, the use of remimazolam is expected to increase providing safe general anesthesia and sedation. This review aims to provide an overview of the basic and clinical pharmacology of remimazolam and to compare it with midazolam and propofol.

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Development and validation of an HPLC-MS/MS assay for the quantitative analysis of remimazolam in critically ill patients

Chen

Xiao³

et al. 2023

International Journal of Mass Spectrometry

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How general anesthetics work: from the perspective of reorganized connections within the brain

Abstract: This article has been accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination, and proofreading processes, which may lead to differences between this version and the version of record.

Cited by 4 publications

References 114 publications

The Rise of Remimazolam: A Review of Pharmacology, Clinical Efficacy, and Safety Profiles

The Rise of Remimazolam: A Review of Pharmacology, Clinical Efficacy, and Safety Profiles

Remimazolam – current knowledge on a new intravenous benzodiazepine anesthetic agent

Development and validation of an HPLC-MS/MS assay for the quantitative analysis of remimazolam in critically ill patients

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