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Oncotarget Feb 2017
Topics: Allosteric Site; Anesthetics; Animals; Binding Sites; DNA Mutational Analysis; Etomidate; Humans; Ions; Mutation; Neurotransmitter Agents; Oocytes; Pentobarbital; Propofol; Protein Domains; Protein Isoforms; Receptors, GABA-A; Xenopus
PubMed: 28099926
DOI: 10.18632/oncotarget.14616 -
Anesthesiology Nov 2016Etomidate potently suppresses adrenocortical steroid synthesis with potentially deleterious consequences by binding to 11β-hydroxylase and inhibiting its function. The...
BACKGROUND
Etomidate potently suppresses adrenocortical steroid synthesis with potentially deleterious consequences by binding to 11β-hydroxylase and inhibiting its function. The authors hypothesized that other sedative-hypnotics currently in clinical use or under development (or their metabolites) might bind to the same site at clinically relevant concentrations. The authors tested this hypothesis by defining etomidate's affinity for this site and the potencies with which other sedative-hypnotics (and their metabolites) inhibit etomidate binding.
METHODS
H-etomidate's binding to adrenal membranes from Sprague-Dawley rats was characterized with a filtration assay, and its dissociation constant was defined using saturation and homologous ligand competition approaches. Half-inhibitory concentrations of sedative-hypnotics and metabolites were determined from the reduction in specific H-etomidate binding measured in the presence of ranging sedative-hypnotic and metabolite concentrations.
RESULTS
Saturation and homologous competition studies yielded H-etomidate dissociation constants of 40 and 21 nM, respectively. Half-inhibitory concentrations of etomidate and cyclopropyl methoxycarbonyl metomidate (CPMM) differed significantly (26 vs. 143 nM, respectively; P < 0.001), and those of the carboxylic acid (CA) metabolites etomidate-CA and CPMM-CA were greater than or equal to 1,000× higher than their respective parent hypnotics. The half-inhibitory concentration of dexmedetomidine was 2.2 µM, whereas those of carboetomidate, ketamine, and propofol were greater than or equal to 50 µM.
CONCLUSION
Etomidate's in vitro dissociation constant for 11β-hydroxylase closely approximates its in vivo adrenocortical half-inhibitory concentration. CPMM produces less adrenocortical suppression than etomidate not only because it is metabolized faster but also because it binds to 11β-hydroxylase with lower affinity. Other sedative-hypnotics and metabolites bind to 11β-hydroxylase and inhibit etomidate binding only at suprahypnotic concentrations.
Topics: Adrenal Cortex; Anesthetics, Dissociative; Animals; Etomidate; Hypnotics and Sedatives; Ketamine; Models, Animal; Propofol; Pyrroles; Rats; Rats, Sprague-Dawley; Steroid 11-beta-Hydroxylase; Structure-Activity Relationship
PubMed: 27541316
DOI: 10.1097/ALN.0000000000001304 -
Physiological Research Apr 2023Increased incidence of postoperative cognitive dysfunction (POCD) is observed in elderly patients underwent intravenous anesthesia (TIVA) with endotracheal intubation.... (Randomized Controlled Trial)
Randomized Controlled Trial
Increased incidence of postoperative cognitive dysfunction (POCD) is observed in elderly patients underwent intravenous anesthesia (TIVA) with endotracheal intubation. Modulation of anesthetics compatibility may reduce the severity of POCD. Elderly patients scheduled for TIVA with endotracheal intubation were randomly divided into the control group (1.00?2.00 mg/kg propofol) and the etomidate and propofol combination group (1.00?2.00 mg/kg propofol and 0.30 mg/kg etomidate). Serum cortisol, S100?, and neuron-specific enolase (NSE), interleukin (IL)-6, and IL-10 were monitored during or after the operation. Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were utilized to assess the severity of POCD. 63 elderly patients in the etomidate and propofol combination group and 60 patients in the control group were enrolled, and there was no significant difference in gender, American Society of Anesthesiologists (ASA) physical status, surgical specialty, intraoperative blood loss, and operation time between the two groups. Significantly increased serum cortisol, S100?, NSE, IL-6, and reduced MMSE and MoCA scores were detected in the control group at different time points after the operation (0-72 h post operation) when compared to those before the operation. Similar trends for these observed factors were found in the etomidate and propofol combination group. In addition, the etomidate and propofol combination group showed better effects in reducing the serum levels of cortisol, S100?, NSE, IL-6, and increasing the MMSE and MoCA scores when compared to the control group. The present study demonstrates that the combination of propofol with etomidate could alleviate POCD in elderly patients underwent TIVA with endotracheal intubation anesthesia.
Topics: Aged; Humans; Postoperative Cognitive Complications; Etomidate; Propofol; Anesthesia, Intravenous; Hydrocortisone; Interleukin-6; Anesthesia, General
PubMed: 37159858
DOI: 10.33549/physiolres.934983 -
Hormones & Cancer Dec 2011Due to broader use of conventional imaging techniques, adrenal tumors are detected with increasing frequency comprising a wide variety of different tumor entities.... (Review)
Review
Due to broader use of conventional imaging techniques, adrenal tumors are detected with increasing frequency comprising a wide variety of different tumor entities. Despite improved conventional imaging techniques, a significant number of adrenal lesions remain that cannot be easily determined. A particular diagnostic challenge are lesions in patients with known extra-adrenal malignancy because these patients frequently harbor adrenal metastases. Furthermore, adrenal masses with low fat content and no detectable hormone excess are difficult to diagnose properly. Fine needle biopsy is invasive, often unsuccessful, and puts patients at risk, e. g., in cases of pheochromocytoma or adrenal cancer. Noninvasive characterization using radiotracers has therefore been established in recent years. (18)F-FDG PET helps to differentiate benign from malignant lesions. However, it does not distinguish between adrenocortical or nonadrenocortical lesions (e.g., metastases or adrenocortical carcinoma). More recently, enzyme inhibitors have been developed as tracers for adrenal imaging. Metomidate is most widely used. It binds with high specificity and affinity to CYP11B enzymes of the adrenal cortex. As these enzymes are exclusively expressed in adrenocortical cells, uptake of labeled metomidate tracers has been shown to be highly specific for adrenocortical neoplasia. (11)C-metomidate PET and (123)I-iodometomidate SPECT imaging has been introduced into clinical use. Both tracers not only distinguish between adrenocortical and nonadrenocortical lesions but are also able to visualize metastases of adrenocortical carcinoma. The very specific uptake has recently led to first application of (131)I-iodometomidate for radiotherapy in ACC. In conclusion, metomidate-based imaging is an important complementary tool to diagnose adrenal lesions that cannot be determined by other methods.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Adrenocortical Carcinoma; Animals; Carbon Radioisotopes; Diagnosis, Differential; Early Detection of Cancer; Etomidate; Humans; Neoplasm Metastasis; Pheochromocytoma; Positron-Emission Tomography; Radioactive Tracers; Steroid 11-beta-Hydroxylase; Tomography, Emission-Computed, Single-Photon
PubMed: 22124841
DOI: 10.1007/s12672-011-0093-3 -
Current Opinion in Endocrinology,... Jun 2015Primary aldosteronism is increasingly recognized as a common secondary cause of hypertension. Successful demonstration of a unilateral cause (e.g. a classical 'Conn's... (Review)
Review
PURPOSE OF REVIEW
Primary aldosteronism is increasingly recognized as a common secondary cause of hypertension. Successful demonstration of a unilateral cause (e.g. a classical 'Conn's adenoma') offers the potential for curative adrenalectomy. Adrenal vein sampling (AVS), in conjunction with cross-sectional imaging, remains the 'gold standard' for distinguishing unilateral and bilateral disease, but is technically demanding and frequently unsuccessful or inconclusive. As such, alternative strategies for lateralization, including nuclear medicine techniques, are being developed and brought into clinical practice.
RECENT FINDINGS
Metomidate, a potent ligand of CYP11B1 and CYP11B2, can be C11H3-labelled as a PET tracer and has been shown to offer a rapid noninvasive alternative to AVS for localizing unilateral aldosterone-producing adenomas.
SUMMARY
Increasing experience with 11C-metomidate PET-CT supports its use as an adjunct to AVS when this has failed, is ambiguous, or cannot be undertaken.
Topics: Etomidate; Humans; Hyperaldosteronism; Positron-Emission Tomography
PubMed: 25871964
DOI: 10.1097/MED.0000000000000148 -
Academic Emergency Medicine : Official... Jan 1995
Topics: Adrenal Glands; Anesthesia, Intravenous; Emergencies; Etomidate; Humans; Intubation, Intratracheal
PubMed: 7606618
DOI: 10.1111/j.1553-2712.1995.tb03089.x -
The Journal of ECT Jun 2023Etomidate and methohexital are the 2 commonly used anesthetics for electroconvulsive therapy (ECT) in the United States. The objective of this study was to examine how...
OBJECTIVE
Etomidate and methohexital are the 2 commonly used anesthetics for electroconvulsive therapy (ECT) in the United States. The objective of this study was to examine how anesthetic choice between etomidate and methohexital is associated with real-world clinical outcomes.
METHODS
This naturalistic retrospective cohort study examined longitudinal electronic health records for 495 adult patients who received 2 or more ECT treatments from 2010 to 2019 in Kaiser Permanente North California, a large integrated health care system. Study outcomes included 12-month posttreatment depression remission as measured by the 9-item Patient Health Questionnaire, psychiatric and all-cause emergency department visits, and psychiatric and all-cause hospitalizations.
RESULTS
Anesthetic choice was not significantly related to depression severity, emergency department visits, or psychiatric hospitalizations at 12 months after completing ECT. In exploratory analyses, we found that etomidate compared with methohexital was associated with higher rates of patient discomfort adverse effects-postictal agitation, phlebitis, and myoclonus (2.4% vs 0.4%; P < 0.001).
CONCLUSIONS
We present the first large comparison of etomidate and methohexital as anesthetics for ECT and their associations with real-world outcomes. Our study showed no significant difference on depression remission, emergency department visits, or hospitalizations 12-months posttreatment. Thus, clinicians should focus on other patient or treatment characteristics when deciding on anesthetics for ECT. Further investigation is needed to confirm our exploratory findings that etomidate use was correlated with a higher rate of patient discomfort adverse effects relative to methohexital.
Topics: Adult; Humans; Anesthetics, Intravenous; Etomidate; Methohexital; Electroconvulsive Therapy; Propofol; Retrospective Studies
PubMed: 36729716
DOI: 10.1097/YCT.0000000000000895 -
British Journal of Anaesthesia Sep 2010Although well established in clinical practice, both propofol and midazolam have limitations. New hypnotics with different and potentially superior pharmacokinetics and... (Review)
Review
Although well established in clinical practice, both propofol and midazolam have limitations. New hypnotics with different and potentially superior pharmacokinetics and pharmacodynamics are under development. These include the benzodiazepine receptor agonists CNS7056 and JM-1232 (-), the etomidate-based methoxycarbonyl-etomidate and carboetomidate, the propofol-related structures PF0713 and fospropofol, and THRX-918661/AZD3043. The basic pharmacology and the initial anaesthesia studies for each of these agents are reviewed. Several of the agents (CNS7056, THRX-918661/AZD3043, and fospropofol) have reached the stage of clinical trials. To be successful, novel compounds need to establish clear clinical advantages over existing agents and where possible the new agents are discussed in this context. Computer-controlled drug administration offers the ability to automatically implement infusion schemes too complex for manual use and the possibility of linking patient monitoring to administration to enhance patient safety.
Topics: Anesthesia, Intravenous; Anesthetics, Intravenous; Drug Delivery Systems; Etomidate; GABA-A Receptor Agonists; Humans
PubMed: 20650920
DOI: 10.1093/bja/aeq190 -
Pediatric Endocrinology, Diabetes, and... 2022The purpose of this work was to present the current state of knowledge on the effects of frequently used therapeutic forms, selected pharmacotherapy (including... (Review)
Review
The purpose of this work was to present the current state of knowledge on the effects of frequently used therapeutic forms, selected pharmacotherapy (including glucocorticosteroids, immune checkpoint inhibitors, mitotane, metyrapone, aminoglutetimide, etomidate, ketoconazole, fluconazole), but also radiation therapy on the functioning of the hypothalamic-pituitary-adrenal axis in children and adolescent during and after oncological treatment. The most common pediatric cancers, where complications of adrenal insufficiency occur, are presented. Moreover, current recommendations how to diagnose the function of the adrenal axis in oncological pediatric patients, as well during oncological treatment as after it, including patients treated with steroids and also patients in severe stages, are reported. The rules of the treatment of adrenal dysfunction in those patients are presented. This understanding is of key importance for oncologists and endocrinologists in the process of diagnosing, treating and developing patient health care, as well as during therapy as after it, offering safety and improving the quality of life.
Topics: Adolescent; Adrenal Glands; Child; Etomidate; Fluconazole; Humans; Hypothalamo-Hypophyseal System; Immune Checkpoint Inhibitors; Ketoconazole; Metyrapone; Mitotane; Pituitary-Adrenal System; Quality of Life
PubMed: 36134674
DOI: 10.5114/pedm.2022.118319 -
Anesthesiology Nov 2014
Topics: Anesthetics, Intravenous; Cardiac Surgical Procedures; Etomidate; Female; Humans; Male; Postoperative Complications
PubMed: 25335176
DOI: 10.1097/ALN.0000000000000418