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https://www.readbyqxmd.com/read/29155148/functional-properties-and-mechanism-of-action-of-pptq-an-allosteric-agonist-and-low-nanomolar-positive-allosteric-modulator-at-gabaa-receptors
#1
Nawid Madjroh, Emma Rie Olander, Christoffer Bundgaard, Pella Cecilia Söderhielm, Anders A Jensen
The former sedative-hypnotic and recreational drug methaqualone (Quaalude) is a moderately potent, non-selective positive allosteric modulator (PAM) at GABAA receptors (GABAARs) (Hammer et al., 2015). In the present study, we have identified a novel methaqualone analog, 2-phenyl-3-(p-tolyl)quinazolin-4(3H)-one (PPTQ), in a screening of 67 analogs at five αβ2γ2S GABAAR subtypes and delineated its functional properties and mechanism of action at wild-type and mutant GABAARs expressed in Xenopus oocytes by two-electrode voltage clamp electrophysiology...
November 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29149702/an-hplc-tandem-mass-spectrometry-for-quantification-of-et-26-hcl-and-its-major-metabolite-in-plasma-and-application-to-a-pharmacokinetic-study-in-rats
#2
Xu Chen, Wensheng Zhang, Sandy Rios, Miriam B Morkos, Xiaoli Ye, Gen Li, Xuehua Jiang, Zhijun Wang, Ling Wang
ET-26-HCl is a new analog of etomidate, a short-acting anesthetic drug, with less adrenal cortex inhibition. The pharmacokinetics of ET-26-HCl in rats needs to be determined for future clinical trials in human subjects. In order to facilitate the pharmacokinetic study, a liquid chromatography based tandem mass spectrometric (HPLC-MS/MS) method was developed and validated for quantification of ET-26-HCl and its major metabolite, ET-26-acid. These two compounds and gabapentin (internal standard) were extracted using a protein precipitation method with methanol and detected by Multiple Reaction Monitoring of m/z transition of 275...
November 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29147790/-etomidate-for-intravenous-induction-of-anaesthesia
#3
C Dumps, D Bolkenius, E Halbeck
The pharmacological and historical knowledge about the currently available intravenous induction hypnotics form the basis for the daily work of anesthetists. Side effects of using hypnotic induction agents must be anticipated and adequately treated. Decades of experience with using intravenous induction hypnotics have led to theoretical requirements for an ideal narcotic agent with a best possible side effect profile. In the absence of this optimal hypnotic induction agent, a careful selection of one or a combination of narcotic drugs is necessary to meet the needs of the respective risk constellation of the patient...
November 16, 2017: Der Anaesthesist
https://www.readbyqxmd.com/read/29064259/the-cardiovascular-implications-of-sedatives-in-the-cardiac-intensive-care-unit
#4
Sammy Zakaria, Helaine J Kwong, Jonathan E Sevransky, Marlene S Williams, Nisha Chandra-Strobos
Patients admitted to the cardiac intensive care unit frequently develop multi-organ system dysfunction associated with their cardiac disease. In many cases, invasive mechanical ventilation is required, which often necessitates sedation for patient-ventilator synchrony, reduction of work of breathing, and patient comfort. In this paper, we describe the use of common sedatives available in the endotracheally intubated critically ill patient and emphasize the clinical and cardiovascular effects. We review γ-aminobutyric acid agonists such as etomidate, benzodiazepines, and propofol, the centrally acting α2-agonist dexmedetomidine, and the N-methyl-D-aspartate receptor antagonist ketamine...
February 1, 2017: European Heart Journal. Acute Cardiovascular Care
https://www.readbyqxmd.com/read/29046518/pretreatment-with-oxycodone-simultaneously-reduces-etomidate-induced-myoclonus-and-rocuronium-induced-withdrawal-movements-during-rapid-sequence-induction
#5
Xiaoxia An, Caixia Li, Zayd Sahebally, Xiaohong Wen, Bing Zhao, Xiangming Fang
BACKGROUND Etomidate and rocuronium are often paired in rapid-sequence anesthesia induction. However, the effect of pretreatment with oxycodone on myoclonic and withdrawal movements has not been previously investigated. The aim of this study was to evaluate the effects of oxycodone on the incidence and severity of etomidate-induced myoclonus and rocuronium-induced nociceptive withdrawal movements during rapid-sequence anesthesia induction. MATERIAL AND METHODS We randomly divided 120 patients into the saline group (group S) and the oxycodone group (group O) (n=60 in each group)...
October 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29039138/the-role-of-gaba-receptor-agonists-in-anesthesia-and-sedation
#6
REVIEW
Janette Brohan, Basavana G Goudra
GABA (γ-aminobutyric acid) receptors, of which there are two types, are involved in inhibitory synapses within the central nervous system. The GABAA receptor (GABAAR) has a central role in modern anesthesia and sedation practice, which is evident from the high proportion of agents that target the GABAAR. Many GABAAR agonists are used in anesthesia practice and sedation, including propofol, etomidate, methohexital, thiopental, isoflurane, sevoflurane, and desflurane. There are advantages and disadvantages to each GABAAR agonist currently in clinical use...
October 2017: CNS Drugs
https://www.readbyqxmd.com/read/28974833/comparing-hemodynamic-responses-to-diazepam-propofol-and-etomidate-during-anesthesia-induction-in-patients-with-left-ventricular-dysfunction-undergoing-coronary-artery-bypass-graft-surgery-a-double-blind-randomized-clinical-trial
#7
Aria Soleimani, Neda Heidari, Mohammad Reza Habibi, Farshad Hasanzadeh Kiabi, Mohammad Khademloo, Amir Emami Zeydi, Fatemeh Bozorg Sohrabi
BACKGROUND: Anesthesia induction is often accompanied by a period of hemodynamic instability, which could be deleterious in patients with coronary artery disease (CAD) and left ventricular dysfunction undergoing coronary artery bypass graft (CABG) surgery. The aim of this study was to compare the hemodynamic responses to propofol, etomidate, and diazepam following anesthesia induction, laryngoscopy and intubation in CABG surgery patients with low ejection fraction (EF). METHODS: A double-blind randomized, clinical study was performed on 150 patients with CAD and left ventricular dysfunction (EF≤35%) scheduled for elective CABG surgery with Cardiopulmonary bypass (CPB)...
June 2017: Medical Archives
https://www.readbyqxmd.com/read/28971155/comparison-of-ketamine-propofol-ketofol-and-etomidate-fentanyl-etofen-combinations-for-procedural-sedation-and-analgesia-in-the-emergency-department-an-observational-study
#8
Erkman Sanri, Sinan Karacabey, Haldun Akoglu, Bora Kaya, Ozlem Guneysel
OBJECTIVES: The primary aim of this study was to report the vital signs, hemodynamic parameters and pain scores of the patients who have received procedural sedation and analgesia (PSA) with either ketofol (combination of ketamine and propofol) or etofen (combination of etomidate and fentanyl) and compare the proportion of patients with airway or respiratory adverse events (AEs) requiring an intervention and calculate the relative risk of AEs with each combination. METHODS: This study is a prospective observational study with survey analysis...
September 2017: Turkish Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28890850/minimum-infusion-rate-and-adrenocortical-function-after-continuous-infusion-of-the-novel-etomidate-analog-et-26-hcl-in-rats
#9
Junli Jiang, Bin Wang, Zhaoqiong Zhu, Jun Yang, Jin Liu, Wensheng Zhang
BACKGROUND: Because etomidate induces prolonged adrenal suppression, even following a single bolus, its use as an infused anesthetic is limited. Our previous study indicated that a single administration of the novel etomidate analog methoxyethyletomidate hydrochloride (ET-26-HCl) shows little suppression of adrenocortical function. The aims of the present study were to (1) determine the minimum infusion rate of ET-26-HCl and compare it with those for etomidate and cyclopropyl-methoxycarbonylmetomidate (CPMM), a rapidly metabolized etomidate analog that is currently in clinical trials and (2) to evaluate adrenocortical function after a continuous infusion of ET-26-HCl as part of a broader study investigating whether this etomidate analog is suitable for long infusion in the maintenance of anesthesia...
2017: PeerJ
https://www.readbyqxmd.com/read/28883852/a-randomized-clinical-trial-comparing-hemodynamic-responses-to-ketamine-propofol-combination-ketofol-versus-etomidate-during-anesthesia-induction-in-patients-with-left-ventricular-dysfunction-undergoing-coronary-artery-bypass-graft-surgery
#10
Afshin Gholipour Baradari, Abbas Alipour, Mohammad Reza Habibi, Sajedeh Rashidaei, Amir Emami Zeydi
INTRODUCTION: Anesthesia induction is often accompanied by a period of hemodynamic instability, which could be a significant problem in patients with compromised ventricular function. The aim of this study is to compare the hemodynamic responses to etomidate versus a combination of ketamine and propofol (ketofol) for anesthetic induction in patients with left ventricular dysfunction undergoing coronary artery bypass graft (CABG) surgery. MATERIAL AND METHODS: In a double-blind randomized clinical study, a total of 84 patients with ischemic left ventricular dysfunction (EF < 40%) were randomly assigned to two groups (A and B)...
August 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28882766/pharmacologic-studies-on-et-26-hydrochloride-in-a-rat-model-of-lipopolysaccharide-induced-sepsis
#11
Bin Wang, Junli Jiang, Jun Yang, Jun Chen, Zhaoqiong Zhu, Jin Liu, Wensheng Zhang
BACKGROUND: ET-26 hydrochloride (ET-26 HCl) is a promising sedation-hypnotic compound with stable hemodynamic features that elicits virtually no adrenocortical suppression. However, whether it preserves better pharmacologic characteristics in a rat model of sepsis is not known. This study compared the survival rate, levels of corticosterone and pro-inflammatory cytokines, and histologic injury in the lungs and kidneys of rats suffering from sepsis treated with ET-26 HCl, etomidate, or normal saline (NS)...
September 4, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28857763/competitive-antagonism-of-anesthetic-action-at-the-%C3%AE-aminobutyric-acid-type-a-receptor-by-a-novel-etomidate-analog-with-low-intrinsic-efficacy
#12
Celena Ma, Ervin Pejo, Megan McGrath, Selwyn S Jayakar, Xiaojuan Zhou, Keith W Miller, Jonathan B Cohen, Douglas E Raines
BACKGROUND: The authors characterized the γ-aminobutyric acid type A receptor pharmacology of the novel etomidate analog naphthalene-etomidate, a potential lead compound for the development of anesthetic-selective competitive antagonists. METHODS: The positive modulatory potencies and efficacies of etomidate and naphthalene-etomidate were defined in oocyte-expressed α1β3γ2L γ-aminobutyric acid type A receptors using voltage clamp electrophysiology. Using the same technique, the ability of naphthalene-etomidate to reduce currents evoked by γ-aminobutyric acid alone or γ-aminobutyric acid potentiated by etomidate, propofol, pentobarbital, and diazepam was quantified...
November 2017: Anesthesiology
https://www.readbyqxmd.com/read/28855151/florida-executes-prisoner-with-etomidate-despite-drug-maker-s-concerns
#13
Owen Dyer
No abstract text is available yet for this article.
August 30, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28826968/-comparison-of-granisetron-and-lidocaine-on-reducing-injection-pain-of-etomidate-a-controlled-randomized-study
#14
Alireza Saliminia, Omid Azimaraghi, Amir Javadi, Maryam Abdoulahpoor, Ali Movafegh
BACKGROUND AND OBJECTIVES: Reducing pain on injection of anesthetic drugs is of importance to every anesthesiologist. In this study we pursued to define if pretreatment by granisetron reduces the pain on injection of etomidate similar to lidocaine. METHODS: Thirty patients aged between 18 and 50 years of American Society of Anesthesiologists physical status class I or II, whom were candidates for elective laparoscopic cholecystectomy surgery were enrolled in this study...
August 18, 2017: Revista Brasileira de Anestesiologia
https://www.readbyqxmd.com/read/28826547/etomidate-coming-to-an-endoscopy-unit-near-you
#15
EDITORIAL
John J Vargo
No abstract text is available yet for this article.
September 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/28814247/fluid-and-medication-considerations-in-the-traumatized-patient
#16
Amita Misir
This article reviews fluid therapy and medications in pediatric trauma. For resuscitation in the setting of hemorrhagic shock, isotonic crystalloid solution is the first-line agent of choice. Colloid solutions offer no additional benefit, introduce possible increased risks and cost more than crystalloids. Blood products, starting with pRBCs, should be introduced after 20-40 ml/kg of crystalloid has been administered if there is ongoing need for volume replacement. The use of a massive transfusion protocol of 1:1:1 (if >30 kg) or 30:20:20 (if <30 kg) of pRBCs:FFP:platelets is suggested after an initial 30 ml/kg of pRBcs have been administered...
August 14, 2017: Current Pediatric Reviews
https://www.readbyqxmd.com/read/28813523/et-26-hydrochloride-et-26-hcl-has-similar-hemodynamic-stability-to-that-of-etomidate-in-normal-and-uncontrolled-hemorrhagic-shock-uhs-rats
#17
Bin Wang, Shouming Chen, Jun Yang, Linghui Yang, Jin Liu, Wensheng Zhang
OBJECTIVE: ET-26 HCl is a promising sedative-hypnotic anesthetic with virtually no effect on adrenocortical steroid synthesis. However, whether or not ET-26 HCl also has a sufficiently wide safety margin and hemodynamic stability similar to that of etomidate and related compounds remains unknown. In this study, the effects of ET-26 HCl, etomidate and propofol on therapeutic index, heart rate (HR), mean arterial pressure (MAP), maximal rate for left ventricular pressure rise (Dmax/t), and maximal rate for left ventricular pressure decline (Dmin/t) were investigated in healthy rats and a rat model of uncontrolled hemorrhagic shock (UHS)...
2017: PloS One
https://www.readbyqxmd.com/read/28803966/a-chimeric-prokaryotic-eukaryotic-pentameric-ligand-gated-ion-channel-reveals-interactions-between-the-extracellular-and-transmembrane-domains-shape-neurosteroid-modulation
#18
Borna Ghosh, Tzu-Wei Tsao, Cynthia Czajkowski
Pentameric ligand-gated ion channels (pLGICs) are the targets of several clinical and endogenous allosteric modulators including anesthetics and neurosteroids. Molecular mechanisms underlying allosteric drug modulation are poorly understood. Here, we constructed a chimeric pLGIC by fusing the extracellular domain (ECD) of the proton-activated, cation-selective bacterial channel GLIC to the transmembrane domain (TMD) of the human ρ1 chloride-selective GABAAR, and tested the hypothesis that drug actions are regulated locally in the domain that houses its binding site...
October 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28769117/species-specific-anaesthetics-for-fish-anaesthesia-and-euthanasia
#19
Gareth D Readman, Stewart F Owen, Toby G Knowles, Joanna C Murrell
There is a need to ensure that the care and welfare for fish maintained in the laboratory are to the highest standards. This extends to the use of anaesthetics for both scientific study, humane killing and euthanasia at end of life. An anaesthetic should not induce negative behaviours and fish should not seek to avoid the anaesthetic. Surprisingly little information is available to facilitate a humane choice of anaesthetic agent for fish despite over 100 years of use and the millions of fish currently held in thousands of laboratories worldwide...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28767661/impact-of-stress-fear-and-anxiety-on-the-nociceptive-responses-of-larval-zebrafish
#20
Javier Lopez-Luna, Qussay Al-Jubouri, Waleed Al-Nuaimy, Lynne U Sneddon
Both adult and larval zebrafish have been demonstrated to show behavioural responses to noxious stimulation but also to potentially stress- and fear or anxiety- eliciting situations. The pain or nociceptive response can be altered and modulated by these situations in adult fish through a mechanism called stress-induced analgesia. However, this phenomenon has not been described in larval fish yet. Therefore, this study explores the behavioural changes in larval zebrafish after noxious stimulation and exposure to challenges that can trigger a stress, fear or anxiety reaction...
2017: PloS One
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