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Benoit Bailey - One of the best experts on this subject based on the ideXlab platform.
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experts consensus recommendations for the management of calcium Channel Blocker poisoning in adults
Critical Care Medicine, 2017Co-Authors: Maude Stonge, William Kerns, Sophie Gosselin, Benoit Bailey, Kurt Anseeuw, Frank Lee Cantrell, Ian C Gilchrist, Philippe Hantson, Valery Lavergne, Martin LaliberteAbstract:To provide a management approach for adults with calcium Channel Blocker poisoning. Following the Appraisal of Guidelines for Research & Evaluation II instrument, initial voting statements were constructed based on summaries outlining the evidence, risks, and benefits. We recommend 1) for asymptomatic patients, observation and consideration of decontamination following a potentially toxic calcium Channel Blocker ingestion (1D); 2) as first-line therapies (prioritized based on desired effect), IV calcium (1D), high-dose insulin therapy (1D-2D), and norepinephrine and/or epinephrine (1D). We also suggest dobutamine or epinephrine in the presence of cardiogenic shock (2D) and atropine in the presence of symptomatic bradycardia or conduction disturbance (2D); 3) in patients refractory to the first-line treatments, we suggest incremental doses of high-dose insulin therapy if myocardial dysfunction is present (2D), IV lipid-emulsion therapy (2D), and using a pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block without significant alteration in cardiac inotropism (2D); 4) in patients with refractory shock or who are periarrest, we recommend incremental doses of high-dose insulin (1D) and IV lipid-emulsion therapy (1D) if not already tried. We suggest venoarterial extracorporeal membrane oxygenation, if available, when refractory shock has a significant cardiogenic component (2D), and using pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block in the absence of myocardial dysfunction (2D) if not already tried; 5) in patients with cardiac arrest, we recommend IV calcium in addition to the standard advanced cardiac life-support (1D), lipid-emulsion therapy (1D), and we suggest venoarterial extracorporeal membrane oxygenation if available (2D). We offer recommendations for the stepwise management of calcium Channel Blocker toxicity. For all interventions, the level of evidence was very low.
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glucagon in β Blocker and calcium Channel Blocker overdoses a systematic review
Clinical Toxicology, 2003Co-Authors: Benoit BaileyAbstract:AbstractBackground. Glucagon is usually accepted as part of the standard treatment in the management of patients with β‐Blocker and calcium Channel Blocker overdoses. Methods. A systematic review was done in order to evaluate the evidence supporting glucagon use in β‐Blocker and calcium Channel Blocker overdoses. Studies evaluating glucagon for those uses were identified using the Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Register, MedLine, ToxLine, and EMBASE searches, as well as reviewing medical toxicology textbooks and references of identified articles. Only controlled studies of human or animal studies were included, the latter only when it was an in vivo model of acute poisoning. The quality of the included studies was assessed. Results. The search found no study in humans but identified 30 in animals. In the five studies of animal models of β‐Blocker overdose included, glucagon appeared to consistently increase the heart rate at least transiently but appeared to have n...
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glucagon in beta Blocker and calcium Channel Blocker overdoses a systematic review
Clinical Toxicology, 2003Co-Authors: Benoit BaileyAbstract:AbstractBackground. Glucagon is usually accepted as part of the standard treatment in the management of patients with β‐Blocker and calcium Channel Blocker overdoses. Methods. A systematic review was done in order to evaluate the evidence supporting glucagon use in β‐Blocker and calcium Channel Blocker overdoses. Studies evaluating glucagon for those uses were identified using the Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Register, MedLine, ToxLine, and EMBASE searches, as well as reviewing medical toxicology textbooks and references of identified articles. Only controlled studies of human or animal studies were included, the latter only when it was an in vivo model of acute poisoning. The quality of the included studies was assessed. Results. The search found no study in humans but identified 30 in animals. In the five studies of animal models of β‐Blocker overdose included, glucagon appeared to consistently increase the heart rate at least transiently but appeared to have n...
Dingxin Jiang - One of the best experts on this subject based on the ideXlab platform.
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discovery of a novel series of tricyclic oxadiazine 4a methyl esters based on indoxacarb as potential sodium Channel Blocker modulator insecticides
Journal of Agricultural and Food Chemistry, 2019Co-Authors: Jianqiang Zhang, Wenbo Hao, Dingxin JiangAbstract:Indoxacarb, a commercialized oxadiazine insecticide, nearly irreversibly blocks open/inactivated, but not resting sodium Channels. The structure-activity relationships showed that the substituents at the position of the chiral atom in the oxadiazine ring are very important to the biological activity of oxadiazine insecticide. Here we synthesized a series of tricyclic oxadiazine 4a-methyl ester derivatives. The chiral atom in the oxadiazine ring has been epimerized and substituted with either pyrethric acid or cinnamic acid derivatives. Benzene ring in the tricyclic moiety was substituted with a chlorine, fluorine, or bromine atom, and nitrogen-linked benzene ring was substituted with a trifluoromethyl or trifluoromethoxy group. Toxicity of these compounds against Spodoptera litura F. was evaluated. Diastereoisomers of most toxic compounds J7 and J9 with pyrethric acid moiety were separated by flash column chromatography. The more polar diastereoisomers, J7-L-Rf and J9-L-Rf, and compounds J24 and J26 with cinnamic acid moiety exhibited highest insecticidal activities. We further used Monte Carlo energy minimizations to dock compound J7 and J24 in the NavMs-based homology model of the open cockroach sodium Channel. In the low-energy binding modes, the compound interacted with residues in the inner pore and domain interfaces, which previously were proposed to contribute to receptors of pyrethroids and sodium Channel Blocker insecticides. Our results define compound J7 and J24 as a potentially useful optimized hit for the development of multiple sites sodium Channel Blocker or modulator.
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The Receptor Site and Mechanism of Action of Sodium Channel Blocker Insecticides
Journal of Biological Chemistry, 2016Co-Authors: Yongqiang Zhang, Yoshiko Nomura, Boris S Zhorov, Dingxin Jiang, Caitlyn Behnke, Ke DongAbstract:Sodium Channels are excellent targets of both natural and synthetic insecticides with high insect selectivity. Indoxacarb, its active metabolite DCJW, and metaflumizone (MFZ) belong to a relatively new class of sodium Channel Blocker insecticides (SCBIs) with a mode of action distinct from all other sodium Channel-targeting insecticides, including pyrethroids. Electroneutral SCBIs preferably bind to and trap sodium Channels in the inactivated state, a mechanism similar to that of cationic local anesthetics. Previous studies identified several SCBI-sensing residues that face the inner pore of sodium Channels. However, the receptor site of SCBIs, their atomic mechanisms, and the cause of selective toxicity of MFZ remain elusive. Here, we have built a homology model of the open-state cockroach sodium Channel BgNav1-1a. Our computations predicted that SCBIs bind in the inner pore, interact with a sodium ion at the focus of P1 helices, and extend their aromatic moiety into the III/IV domain interface (fenestration). Using model-driven mutagenesis and electrophysiology, we identified five new SCBI-sensing residues, including insect-specific residues. Our study proposes the first three-dimensional models of Channel-bound SCBIs, sheds light on the molecular basis of MFZ selective toxicity, and suggests that a sodium ion located in the inner pore contributes to the receptor site for electroneutral SCBIs.
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Design, synthesis and structure-activity relationship of indoxacarb analogs as voltage-gated sodium Channel Blocker.
Bioorganic & Medicinal Chemistry Letters, 2015Co-Authors: Wenbo Hao, Chen Jian, Guang Shao, Dingxin JiangAbstract:Indoxacarb, the first commercialized pyrazoline-type sodium-Channel Blocker, is a commonly used insecticide because of high selectivity. To discover sodium-Channel Blocker with high insecticidal activity, a series of novel indoxacarb analogs were designed and synthesized by judicious structural modifications of the substituent group of C5, C6 in indenone and C'4 in benzene ring. Some analogs exhibited significant insecticidal activities against Spodoptera litura F. and excellent BgNav1-1a Channel inhibitory activity. The structure-activity analysis indicated that the presence of strong electron-withdrawing group and decreased steric hindrance of indenone ring (R(1), R(2)) in 5- and 6-position could enhance larvicidal activity and BgNav1-1a Channel inhibitory activity.
Joel S Holger - One of the best experts on this subject based on the ideXlab platform.
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high dose insulin therapy in beta Blocker and calcium Channel Blocker poisoning
Clinical Toxicology, 2011Co-Authors: Kristin M Engebretsen, Kathleen M Kaczmarek, Jenifer Morgan, Joel S HolgerAbstract:Introduction. High-dose insulin therapy, along with glucose supplementation, has emerged as an effective treatment for severe betaBlocker and calcium Channel-Blocker poisoning. We review the experimental data and clinical experience that suggests high-dose insulin is superior to conventional therapies for these poisonings. Presentation and general management. Hypotension, bradycardia, decreased systemic vascular resistance (SVR), and cardiogenic shock are characteristic features of beta-Blocker and calcium-Channel Blocker poisoning. Initial treatment is primarily supportive and includes saline fluid resuscitation which is essential to correct vasodilation and low cardiac filling pressures. Conventional therapies such as atropine, glucagon and calcium often fail to improve hemodynamic status in severely poisoned patients. Catecholamines can increase blood pressure and heart rate, but they also increase SVR which may result in decreases in cardiac output and perfusion of vascular beds. The increased myocardial oxygen demand that results from catecholamines and vasopressors may be deleterious in the setting of hypotension and decreased coronary perfusion. Methods. The Medline, Embase, Toxnet, and Google Scholar databases were searched for the years 1975‐2010 using the terms: highdose insulin, hyperinsulinemia‐euglycemia, beta-Blocker, calcium-Channel Blocker, toxicology, poisoning, antidote, toxin-induced cardiovascular shock, and overdose. In addition, a manual search of the Abstracts of the North American Congress of Clinical Toxicology and the Congress of the European Association of Poisons Centres and Clinical Toxicologists published in Clinical Toxicology for the years 1996‐2010 was undertaken. These searches identified 485 articles of which 72 were considered relevant. Mechanisms of high-dose insulin benefit. There are three main mechanisms of benefit: increased inotropy, increased intracellular glucose transport, and vascular dilatation. Efficacy of high-dose insulin. Animal models have shown high-dose insulin to be superior to calcium salts, glucagon, epinephrine, and vasopressin in terms of survival. Currently, there are no published controlled clinical trials in humans, but a review of case reports and case series supports the use of high-dose insulin as an initial therapy. High-dose insulin treatment protocols. When first introduced, insulin doses were cautiously initiated at 0.5 U/kg bolus followed by a 0.5‐1 U/kg/h continuous infusion due to concern for hypoglycemia and electrolyte imbalances. With increasing clinical experience and the publication of animal studies, high-dose insulin dosing recommendations have been increased to 1 U/kg insulin bolus followed by a 1‐10 U/kg/h continuous infusion. Although the optimal regimen is still to be determined, bolus doses up to 10 U/kg and continuous infusions as high as 22 U/kg/h have been administered with good outcomes and minimal adverse events. Adverse effects of high-dose insulin. The major anticipated adverse events associated with high-dose insulin are hypoglycemia and hypokalemia. Glucose concentrations must be monitored regularly and supplementation of glucose will likely be required throughout therapy and for up to 24 h after discontinuation of high-dose insulin. The change in serum potassium concentrations reflects a shifting of potassium from the extracellular to intracellular space rather than a decrease in total body stores. Conclusions. While more clinical data are needed, animal studies and human case reports demonstrate that high-dose insulin (1‐10 U/kg/ hour) is a superior treatment in terms of safety and survival in both beta-Blocker and calcium-Channel Blocker poisoning. High-dose insulin should be considered initial therapy in these poisonings.
Maude Stonge - One of the best experts on this subject based on the ideXlab platform.
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experts consensus recommendations for the management of calcium Channel Blocker poisoning in adults
Critical Care Medicine, 2017Co-Authors: Maude Stonge, William Kerns, Sophie Gosselin, Benoit Bailey, Kurt Anseeuw, Frank Lee Cantrell, Ian C Gilchrist, Philippe Hantson, Valery Lavergne, Martin LaliberteAbstract:To provide a management approach for adults with calcium Channel Blocker poisoning. Following the Appraisal of Guidelines for Research & Evaluation II instrument, initial voting statements were constructed based on summaries outlining the evidence, risks, and benefits. We recommend 1) for asymptomatic patients, observation and consideration of decontamination following a potentially toxic calcium Channel Blocker ingestion (1D); 2) as first-line therapies (prioritized based on desired effect), IV calcium (1D), high-dose insulin therapy (1D-2D), and norepinephrine and/or epinephrine (1D). We also suggest dobutamine or epinephrine in the presence of cardiogenic shock (2D) and atropine in the presence of symptomatic bradycardia or conduction disturbance (2D); 3) in patients refractory to the first-line treatments, we suggest incremental doses of high-dose insulin therapy if myocardial dysfunction is present (2D), IV lipid-emulsion therapy (2D), and using a pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block without significant alteration in cardiac inotropism (2D); 4) in patients with refractory shock or who are periarrest, we recommend incremental doses of high-dose insulin (1D) and IV lipid-emulsion therapy (1D) if not already tried. We suggest venoarterial extracorporeal membrane oxygenation, if available, when refractory shock has a significant cardiogenic component (2D), and using pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block in the absence of myocardial dysfunction (2D) if not already tried; 5) in patients with cardiac arrest, we recommend IV calcium in addition to the standard advanced cardiac life-support (1D), lipid-emulsion therapy (1D), and we suggest venoarterial extracorporeal membrane oxygenation if available (2D). We offer recommendations for the stepwise management of calcium Channel Blocker toxicity. For all interventions, the level of evidence was very low.
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treatment for calcium Channel Blocker poisoning a systematic review
Clinical Toxicology, 2014Co-Authors: Maude Stonge, Pierreandre Dube, Sophie Gosselin, Chantal Guimont, Jesse Godwin, Patrick Archambault, Jeanmarc Chauny, A J Frenette, M Darveau, Le N SageAbstract:AbstractContext. Calcium Channel Blocker poisoning is a common and sometimes life-threatening ingestion. Objective. To evaluate the reported effects of treatments for calcium Channel Blocker poisoning. The primary outcomes of interest were mortality and hemodynamic parameters. The secondary outcomes included length of stay in hospital, length of stay in intensive care unit, duration of vasopressor use, functional outcomes, and serum calcium Channel Blocker concentrations. Methods. Medline/Ovid, PubMed, EMBASE, Cochrane Library, TOXLINE, International pharmaceutical abstracts, Google Scholar, and the gray literature up to December 31, 2013 were searched without time restriction to identify all types of studies that examined effects of various treatments for calcium Channel Blocker poisoning for the outcomes of interest. The search strategy included the following Keywords: [calcium Channel Blockers OR calcium Channel antagonist OR calcium Channel blocking agent OR (amlodipine or bencyclane or bepridil or ci...
Franz H Messerli - One of the best experts on this subject based on the ideXlab platform.
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effect of renin angiotensin system blockade on calcium Channel Blocker associated peripheral edema
The American Journal of Medicine, 2011Co-Authors: Harikrishna Makani, Sripal Bangalore, Jorge Romero, Omar Weverpinzon, Franz H MesserliAbstract:Abstract Background Peripheral edema is a common adverse effect of calcium Channel Blockers. The addition of a renin-angiotensin system Blocker, either an angiotensin-converting enzyme inhibitor or an ARB, has been shown to reduce peripheral edema in a dose-dependent way. Methods We performed a MEDLINE/COCHRANE search for all prospective randomized controlled trials in patients with hypertension, comparing calcium Channel Blocker monotherapy with calcium Channel Blocker/renin-angiotensin system Blocker combination from 1980 to the present. Trials reporting the incidence of peripheral edema or withdrawal of patients because of edema and total sample size more than 100 were included in this analysis. Results We analyzed 25 randomized controlled trials with 17,206 patients (mean age 56 years, 55% were men) and a mean duration of 9.2 weeks. The incidence of peripheral edema with calcium Channel Blocker/renin-angiotensin system Blocker combination was 38% lower than that with calcium Channel Blocker monotherapy ( P P =.002) (RR 0.38; 95% CI, 0.22-0.66). ACE inhibitors were significantly more efficacious than ARBs in reducing the incidence of peripheral edema ( P Conclusion In patients with hypertension, the calcium Channel Blocker/renin-angiotensin system Blocker combination reduces the risk of calcium Channel Blocker-associated peripheral edema when compared with calcium Channel Blocker monotherapy. ACE inhibitor seems to be more efficacious than ARB in reducing calcium Channel Blocker-associated peripheral edema, but head-to-head comparison studies are needed to prove this.