521 results on '"Etidocaine"'
Search Results
2. Researchers Submit Patent Application, 'Enhanced Solubility Drug-Containing Formulations', for Approval (USPTO 20200054754)
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Physical fitness ,Local anesthetics ,Drug approval ,Chloroprocaine ,Obesity ,Bupivacaine ,Etidocaine ,Editors ,Mepivacaine ,Health - Abstract
2020 MAR 14 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- From Washington, D.C., NewsRx journalists report that a patent application by the [...]
- Published
- 2020
3. 'Drug Delivery System' in Patent Application Approval Process (USPTO 20200038594)
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Drug delivery systems -- Intellectual property ,Physical fitness ,Polidocanol ,Local anesthetics ,Obesity ,Containers ,Benzocaine ,Bupivacaine ,Etidocaine ,Editors ,Mepivacaine ,Dyclonine ,Health - Abstract
2020 FEB 29 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- A patent application by the inventor Cook, Jason (Arden, Nc), filed on [...]
- Published
- 2020
4. Patent Issued for Injectable Long-Acting Local Anesthetic Semi-Solid Formulations And Its Compositions (USPTO 10,500,281)
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Physical fitness ,Local anesthetics ,Obesity ,Morphine ,Bupivacaine ,Etidocaine ,Analgesia ,Editors ,Mepivacaine ,Health - Abstract
2019 DEC 28 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Mira Pharma Corporation (Kenmore, Washington, United States) has been issued patent number [...]
- Published
- 2019
5. Patent Application Titled 'Novel Interstitial Therapy For Immediate Symptom Relief And Chronic Therapy In Interstitial Cystitis' Published Online (USPTO 20190321391)
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Physical fitness ,Local anesthetics ,Interstitial cystitis ,Citrus ,Chloroprocaine ,Obesity ,Benzocaine ,Bupivacaine ,Cystitis ,Etidocaine ,Editors ,Mepivacaine ,Dyclonine ,Health - Abstract
2019 NOV 16 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- According to news reporting originating from Washington, D.C., by NewsRx journalists, a [...]
- Published
- 2019
6. DoE development of ionic gradient liposomes: A successful approach to improve encapsulation, prolong anesthesia and decrease the toxicity of etidocaine.
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Oliveira, Juliana Damasceno, Rodrigues da Silva, Gustavo Henrique, de Moura, Ludmila David, Göethel, Gabriela, Papini, Juliana Z.B., Casadei, Bruna Renata, Ribeiro, Ligia Nunes de Morais, Cabeça, Luis Fernando, Garcia, Solange Cristina, Martinez, Elizabeth Ferreira, Tofoli, Giovana Radomille, and de Paula, Eneida
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LIPOSOMES , *POSTOPERATIVE pain treatment , *DRUG delivery systems , *LOCAL anesthetics , *SCHWANN cells , *ANESTHESIA , *SOY flour - Abstract
[Display omitted] Etidocaine (EDC) is a long-acting local anesthetic of the aminoamide family whose use was discontinued in 2008 for alleged toxicity issues. Ionic gradient liposomes (IGL) are nanostructured carriers for which an inner/outer gradient of ions increases drug upload. This work describes IGL EDC , a formulation optimized by Design of Experiments , composed of hydrogenated soy phosphatidylcholine:cholesterol:EDC, and characterized by DLS, NTA, TEM/Cryo-TEM, DSC and 1H NMR. The optimized IGL showed significant encapsulation efficiency (41 %), good shelf stability (180 days) and evidence of EDC interaction with the lipid bilayer (as seen by DSC and 1H NMR results) that confirms its membrane permeation. In vitro (release kinetics and cytotoxicity) tests showed that the encapsulation of EDC into the IGL promoted sustained release for 24 h and decreased by 50 % the intrinsic toxicity of EDC to Schwann cells. In vivo IGL EDC decreased the toxicity of EDC to Caenorhabditis elegans by 25 % and extended its anesthetic effect by one hour, after infiltrative administration, at clinically used (0.5 %) concentration, in rats. Thus, this novel drug delivery system is a promise for the possible reintroduction of EDC in clinics, aiming at the control of operative and postoperative pain. [ABSTRACT FROM AUTHOR]
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- 2023
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7. Patent Issued for Composition Comprising Hyaluronic Acid And Mepivacaine (USPTO 10,413,637)
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Physical fitness ,Polidocanol ,Amino acids -- Intellectual property ,Skin ,Local anesthetics ,Hyaluronic acid -- Intellectual property ,Chloroprocaine ,Obesity ,Benzocaine ,Bupivacaine ,Etidocaine ,Editors ,Health - Abstract
2019 OCT 5 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- A patent by the inventors Bourdon, Francois (Gaillard, FR); Meunier, Stephane (Thoiry, [...]
- Published
- 2019
8. Patent Issued for Topical Preparation For Pain Relief (USPTO 10,391,074)
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Etoricoxib ,Physical fitness ,Methyl salicylate ,Lumiracoxib ,Nonsteroidal anti-inflammatory agents ,Local anesthetics ,Pain management ,Etidocaine ,Oxaprozin ,Chloroprocaine ,Obesity ,Meclofenamate ,Benzocaine ,Tolmetin ,Diflunisal ,Bupivacaine ,Fenoprofen ,Sulindac ,Analgesia ,Editors ,Health - Abstract
2019 SEP 14 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Sambria Pharmaceuticals LLC (Atlanta, Georgia, United States) has been issued patent number [...]
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- 2019
9. 'Composition Comprising Hyaluronic Acid And Mepivacaine' in Patent Application Approval Process (USPTO 20190184065)
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Physical fitness ,Polidocanol ,Amino acids -- Intellectual property ,Skin ,Local anesthetics ,Hyaluronic acid -- Intellectual property ,Chloroprocaine ,Obesity ,Benzocaine ,Bupivacaine ,Etidocaine ,Editors ,Health - Abstract
2019 JUL 13 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- A patent application by the inventors BOURDON, FRANCOIS (Gaillard, FR); Meunier, Stephane [...]
- Published
- 2019
10. Desenvolvimento de uma formulação à base de lipossomas de gradiente iônico para liberação prolongada da etidocaína
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Oliveira, Juliana Damasceno, 1980, Paula, Eneida de, 1963, Yagui, Carlota de Oliveira Rangel, Barbosa, Leandro Ramos Souza, Marsaioli, Anita Jocelyne, Nascimento, Laura de Oliveira, Universidade Estadual de Campinas. Instituto de Biologia, Programa de Pós-Graduação em Biologia Funcional e Molecular, and UNIVERSIDADE ESTADUAL DE CAMPINAS
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Lipossomos ,Anestésicos locais ,Local anesthetics ,Etidocaína ,Liposomes ,Etidocaine - Abstract
Orientador: Eneida de Paula Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia Resumo: Os anestésicos locais (AL) são capazes de interromper a condução nervosa, impedindo o influxo de sódio através dos canais voltagem-dependentes das membranas excitáveis. A etidocaína (EDC) é um anestésico local de longa duração, cuja suposta toxicidade restringiu seu uso clínico. Os lipossomas podem prolongar o tempo de analgesia e reduzir a toxicidade dos anestésicos locais. Lipossomas de gradiente iônico (IGL) foram propostos para aumentar a capacidade de carregamento e liberação sustentada de fármacos, dos lipossomas. Nesta tese sintetizamos o cloridrato de etidocaína (EDC) para posterior encapsulação em IGL. Três tipos de vesículas lipossomais foram preparadas contendo 250 mM de (NH4)2SO4 no interior aquoso, para encapsulamento de 0,5% de EDC: com fosfatidilcolina de ovo:colesterol: "alfa" tocoferol e com fosfatidilcolina hidrogenada de soja:colesterol (10 e 20 mM), essas últimas otimizadas por planejamento fatorial. Dispersão dinâmica de luz, rastreamento de nanopartículas, ressonância magnética nuclear de hidrogênio (diffusion ordered spectroscopy, saturation-transfer difference), calorimetria diferencial de varredura, microscopia eletrônica de transmissão e ressonância paramagnética eletrônica foram usados para caracterizar: o tamanho, a polidispersão e o potencial elétrico de superfície das nanopartículas, sua concentração, morfologia, fluidez da membrana e capacidade de encapsulação. Testes de cinética da liberação do fármaco, testes de toxicidade in vitro (em células de Schwann e fibroblastos gengivais) e in vivo (em C. elegans e em ratos) também foram realizados. Para determinar o efeito anestésico, foi usado o teste de pressão da pata (PWPT) em ratos Wistar. A formulação otimizada, IGLEDC 20 mM, apresentou população de partículas com diâmetro médio de 450 ± 10 nm, baixa polidispersão (PDI < 0,25), concentração média de 8,5 ± 0,4x1013 partículas/mL, potencial zeta negativo (-25,1 ± 0,7 mV) e esses parâmetros permaneceram estáveis durante armazenamento a 37oC por 180 dias. A eficiência de encapsulação foi de 41% e a formulação induziu liberação sustentada do fármaco (ca. 24 h), reduzindo a toxicidade da EDC sobre células de Schwann in vitro e C. elegans, in vivo. Em ratos, o tempo de anestesia alcançado com etidocaína 0,5% encapsulada em IGL foi 1,5 x maior (130 min) que a induzida pelo fármaco livre. Uma nova formulação farmacêutica é proposta para promover liberação sustentada e redução da toxicidade da etidocaína. IGLEDC pode vir a ser uma ferramenta para reintroduzir a etidocaína no uso clínico Abstract: Local anesthetics (LA) stop nerve conduction by preventing the influx of sodium ions through the voltage-gated channels of excitable membranes. Etidocaine (EDC) is a long-lasting local anesthetic, which alleged toxicity has restricted its clinical use. Liposomes can prolong the analgesia and reduce the toxicity of local anesthetics. Ionic gradient liposomes (IGL) have been proposed to increase the upload and prolong drug release from liposomes. In this thesis, etidocaine was synthesized for further encapsulation into liposomes. Three kinds of liposomes, containing 250 mM (NH4)2SO4 in their inner aqueous core were prepared for the encapsulation of 0.5% EDC: with egg phosphatidylcholine:cholesterol: "alfa"-tocopherol or with hydrogenated soy phosphatidylcholine:cholesterol (10 and 20 mM), the last ones optimized through factorial design. Dynamic light scattering, nanotracking analysis, nuclear magnetic resonance (diffusion ordered spectroscopy, saturation-transfer difference), differential scanning calorimetry, transmission electron microscopy and electron paramagnetic resonance were used to characterize nanoparticles size, polydispersity, zeta potential, concentration, morphology, membrane fluidity and encapsulation efficiency. Release kinetics, in vitro (over Schwann and gingival fibroblasts cells) and in vivo (C. elegans and rats) toxicity tests were also performed. To determine the anesthetic effect, the Paw Withdrawal Threshold to Pressure test (PWPT) was used in Wistar rats. The optimized formulation (IGLEDC 20 mM) showed liposomes with 450 ± 10 nm average diameters, low polydispersity (< 0.25), mean concentration of 8.5 ± 0.4x1013 particles/mL and negative zeta potentials (-25.1 ± 0.7 mV), these parameters remaining stable during 180 days of storage at 37ºC. The encapsulation efficiency was 41% and the formulation induced sustained drug release (ca. 24h), while reducing EDC toxicity to Schwann cells in vitro and to C. elegans in vivo. The total anesthesia time achieved with 0.5% etidocaine in IGL was 1.5 times longer (130 min) than that induced by EDC in solution. A novel pharmaceutical formulation is proposed, to promote sustained release and reduced toxicity of etidocaine. IGLEDC can come to be a tool to reintroduce etidocaine in the clinical practice Doutorado Bioquímica Doutora em Biologia Funcional e Molecular CNPQ 141169/2015-0
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- 2020
11. Local Anesthetics and Anesthetic Solutions: Classification, Mode of Action and Dosages
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Eckart Haneke
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Venipuncture ,Lidocaine ,Etidocaine ,Local anesthetic ,medicine.drug_class ,business.industry ,Procaine ,Anesthesia ,Anesthetic ,medicine ,Dermatologic surgery ,Local anesthesia ,business ,medicine.drug - Abstract
Local anesthetics have revolutionized surgery and many more medical subspecialties. The first local anesthetic ever used was cocaine, which remained for many years the only active substance and also the standard until procaine was synthesized. Local anesthetics are used for surface, infiltration, regional and plexus blocks, epidural, and intrathecal anesthesias. The aim of local anesthesia is to make the skin and mucous membranes, as well as deeper tissues, insensitive to pain. Topical anesthetics are a help for venipuncture, vaccinations, some very superficial procedures, such as curettage, shave excisions, and laser treatments, and a variety of other procedures. Topical anesthetics have gained wide acceptance in dermatologic surgery, but also in pediatrics and wherever there is unbalanced fear of a needle prick. Lidocaine is certainly the most commonly used local anesthetic in dermatologic surgery and has an excellent safety report. Etidocaine is a long-acting local anesthetic that is well tolerated not only for nerve blocks but also for infiltration anesthesia.
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- 2019
12. Sustained Release from Ionic-Gradient Liposomes Significantly Decreases ETIDOCAINE Cytotoxicity
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Oliveira, Juliana Damasceno, Ribeiro, Lígia Nunes de Morais, Rodrigues da Silva, Gustavo Henrique, Casadei, Bruna Renata, Couto, Verônica Muniz, Martinez, Elizabeth Ferreira, and de Paula, Eneida
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- 2018
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13. Cocaine and local anesthetics: Stimulant activity in rats with nigral lesions.
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Silverman, Peter
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Cocaine and several other local anesthetics were tested for their ability to induce rotational behavior in rats with unilateral 6-hydroxydopamine lesions of substantia nigra. Acute administration of bupivacaine, chloroprocaine, etidocaine, lidocaine, mepivacaine, procaine or tetracaine failed to induce active rotation in this sensitive assay of dopamine agonist activity. On the other hand, cocaine or dimethocaine treatment induced active rotation directed ipsilaterally to the lesioned side, indicating indirect dopamine agonist activity. Repeated administration of cocaine or dimethocaine at 1-week intervals resulted in increased rotational response (i.e., sensitization) while there was no suggestion of sensitization or induction of rotational behavior after weekly repeated administration of procaine or tetracaine. Daily administration of mepivacaine, procaine or tetracaine for 5 days also failed to induce rotation. Dimethocaine thus was found similar to cocaine and different from the other local anesthetics tested both in terms of frank stimulant activity and development of sensitization upon repeated administration. [ABSTRACT FROM AUTHOR]
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- 1990
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14. Alcalinisation des anesthésiques locaux: théoriquement justifiée mais inutile cliniquement.
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Chassard, Dominique, Berrada, Khalid, and Boulétreau, Paul
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Objectif: Plusieurs travaux expérimentaux sur des nerfs isolés ont montré que l'inhibition sélective des canaux sodés évoquée par les anesthésiques locaux était potentialisée par l'alcalinisation du bain de conservation. Ce changement de pH augmentait la proportion de la forme non ionisée et modifiait favorablement les caractéristiques du bloc nerveux dont la latence et la puissance. L'alcalinisation in vitro des anesthésiques locaux a été étudiée in vivo depuis les années 1970, les principaux bénéfices cliniques attendus étant une diminution de la latence du bloc anesthésique et une augmentation de leur puissance. Cette étude avait pour objectif de vérifier si les études cliniques confirmaient cette action in vivo. Source: Les auteurs de ce travail de revue de la littérature ont relevé les articles pertinents à l'alcalinisation publiés dans les principaux journaux nords-américains et européens d'anesthésiologie et de pharmacologie publiés depuis 1965. Constatations principales: Les bénéfices attendus soit la diminution de la latence et l'augmentation de la puissance du bloc ne se vérifient pas de façon convaincante in vivo. L'ajout de NaHCO peut en outre produire une précipitation. Conclusions: Les résultats des cliniques sont trop discordants à ce jour pour que cette technique soit recommandée en pratique quotidienne. Purpose: In vitro studies have demonstrated the potential advantages of alkalinization on anaesthetic activity, by decreasing the ratio of ionized to nonionized molecules, thereby permitting more rapid penetration of local anaesthetic through biological membranes, thus decreasing the onset time. The proportion of each form depends on the pKa of the agent and the ultimate pH of the solution. When NaHCO is mixed with local anaesthetics, CO is produced. Carbon dioxide has been reported to enhance local anaesthetic action by diffusion trapping of the cationic form in pH gradient combined with a direct depressant action of CO. The purpose of this study was to examine if clinical studies confirmed the in vitro action of alkalinisation. Source: The literature pertinent to alkalinization of local anaesthetics published in the major anaesthesia and pharmacology journals of North America and Europe. Principal findings: While in vitro studies have demonstrated potential advantages for alkalinization on anaesthetic activity, clinical studies have shown that alkalinization of local anaesthetics produces inconsistent results. For bupivacaine and etidocaine, alkalinization of local anaesthetic solution can produce precipitation, thus limiting the feasibility of increasing the pH. Conclusions: On the basis of this review, routine alkalinization of local anaesthetics is not recommended. [ABSTRACT FROM AUTHOR]
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- 1996
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15. Hydrophobic membrane interaction of etidocaine, bupivacaine and 2-chloroprocaine.
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Rosenberg, Per and Alila, Aira
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It has been suggested that local anesthetics may block sodium conductance through nervous membranes also by hydrophobic interaction, e.g., by expanding the membrane. Decreased anisotropy (fluidization) and depressed phase transition temperatures have been shown by relatively high local anesthetic concentrations. We studied the dose dependence of the effect of three clinically used local anesthetics, with different lipid solubility, on lipid fluidity parameters of four different model membranes. With stearic acid spin labels in dipalmitoyl lecithin vesicles etidocaine (1-5 mM) had the clearest fluidizing effect followed by bupivacaine (5 mM); 2-chloroprocaine was without effect on lipid fluidity. In synaptic plasma membranes a fluidizing effect near the hydrophilic part of the lipid bilayer was similar with etidocaine and bupivacaine (5-10 mM); 2-chloroprocaine had no effect. Bupivacaine at 125 and 250 μM had a small ordering effect, which was not seen at a more hydrophobic site of the membrane. Etidocaine had the strongest fluidizing effect at the latter site of the synaptic plasma membranes. In erythrocyte ghost membranes, probed by stearic acid spin labels near the hydrophilic end, none of local anesthetics affected fluidity at 24° C, while at 37° C etidocaine (1-5 mM) and bupivacaine (5 mM) had a fluidizing effect. Dimyristoyl lecithin vesicles were probed by cis-and trans-parinaric acid. Etidocaine and bupivacaine (5-10 mM) clearly depressed the phase transition temperature evaluated from fluorescence intensity scans. The effect was most marked with bupivacaine (1-10 mM) when dis-parinaric acid was used. While isolated mammalian nerves are blocked by local anesthetic concentrations below 100 μM, this study shows that the clinically used local anesthetics increase fluidity and depress phase transition temperature only at 10-100 times higher concentrations at physiological pH. This kind of hydrophobic membrane interaction may not be important for the nerve blocking effect. [ABSTRACT FROM AUTHOR]
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- 1982
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16. Deamination of released H-noradrenaline in the canine saphenous vein.
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Verbeuren, T. and Vanhoutte, P.
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Experiments were designed to determine the effect of monoamine oxidase (MAO) inhibitors on the release and the metabolism of noradrenaline in the canine saphenous vein. Helical strips were incubated with H-noradrenaline and mounted for superfusion and measurement of the efflux of labelled transmitter and its metabolites; in certain experiments the tissue content of H-noradrenaline and its metabolites was also determined. The MAO-A inhibitor clorgyline, and the non-specific inhibitor pargyline, but not the MAO-B inhibitor deprenyl decreased the appearance of deaminated and O-methylated deaminated metabolites under basal conditions and during electrical stimulation. The MAO-A and the non-specific MAO inhibitor did not decrease the efflux of VMA to the same extent as that of the other deaminated metabolites. During superfusion with etidocaine, an agent causing increased leakage of stored transmitter, clorgyline abolished the appearance of DOPEG. Addition of semicarbazide in preparations treated with pargyline did not affect the efflux of deaminated and O-methylated deaminated metabolites. From the measurement of tissue VMA, it appeared that the efflux of VMA poorly reflects quick changes in the rate of its formation but that formation is abolished by pretreatment with pargyline. These experiments indicate that in the canine saphenous vein: (1) DOPEG is formed mainly in intraneuronal sites, while DOMA, MOPEG and VMA are formed extraneuronally; (2) VMA is retained in the tissue after its formation; and (3) the only subtype of MAO involved in the metabolism of H-noradrenaline released from adrenergic nerve endings can be classified as MAO-A. [ABSTRACT FROM AUTHOR]
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- 1982
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17. Plasma protein binding of etidocaine during pregnancy and labour.
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Morgan, D., Koay, B., and Paull, J.
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Preliminary studies of the ultrafiltration method for measuring the extent of plasma protein binding of etidocaine showed that etidocaine binding was both pH and concentration dependent. Etidocaine (1 µg/ml) was found to bind avidly to a physiological concentration (74 mg/dl) of α-acid glycoprotein (α-AGP) (7.23±0.64%, mean ± SD, unbound). In vitro investigation of etidocaine binding in plasma obtained from blood bank donors and from 19 pregnant women prior to induction of labour, during early labour, mid-labour and delivery showed no difference in etidocaine binding (10.3±3.3%, 7.06±2.66%, 8.15±2.57%, 7.84±3.74% and 9.28±6.06% unbound respectively). There was a significant increase in the mean plasma total free fatty acid (FFA) concentration from pre-labour (0.535±0.240 mM) to delivery (0.948±0.28 mM), while plasma albumin and β-lipoprotein concentrations remained constant. α-Acid glycoprotein concentration tended to increase slightly from pre-labour to early labour ( p<0.1) but was still within the normal physiological range. There was no correlation between etidocaine binding ratio and the concentrations of FFA or plasma proteins except for a poor correlation with the α-AGP concentration ( r=0.361, p<0.05). Storage of plasma and inadequate control of plasma pH during ultrafiltration appeared to give spurious binding values. These studies with the extensively bound basic drug etidocaine suggest that unlike many acidic drugs which are bound predominantly to serum albumin, the binding of α-AGP - bound basic drugs may be unaffected by pregnancy and labour. [ABSTRACT FROM AUTHOR]
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- 1982
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18. Pharmacokinetics and metabolism of the anilide local anaesthetics in neonates. 11 etidocaine.
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Morgan, D., McQuillan, D., and Thomas, J.
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The urinary elimination of etidocaine and several of its metabolites was investigated in neonates whose mothers had received one or more doses of etidocaine during labour. The urine collection period ranged among the neonates from 21.4 to 47.0 h post-partum. The total amounts of etidocaine and its metabolites recovered in neonatal urine represented a mean of 0.12 per cent of the maternal dose. Some differences in the pattern of urinary metabolites were observed between neonates and adults. Mean half-life of elimination of etidocaine calculated from sigma-minus plots of the neonatal urinary data was 6.42 h. This is greater than that previously reported following intravenous administration of etidocaine to adults (2.6 h). The slower rate of elimination in neonates is probably due to an increased neonatal volume of distribution since there is evidence to show that etidocaine is extensively metabolised by the neonate. [ABSTRACT FROM AUTHOR]
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- 1978
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19. Disposition and placental transfer of etidocaine in pregnancy.
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Morgan, D., Cousins, M., McQuillan, D., and Thomas, J.
- Abstract
Following epidural administration of etidocaine hydrochloride to non-pregnant and pregnant patients, a similar rate of absorption was observed and there was no significant difference in total systemic blood clearance (Cl) of etidocaine in the two groups. There were no major differences in the urinary excretion of etidocaine and metabolites in 48 h urine in both groups. The ability of pregnant women to form the N-glucuronide of the metabolite ABX (2-amino-2′-butyroxylidide) was similar to that of non-pregnant individuals. In vitro experiments showed that the blood/plasma concentration ratio (λ) of etidocaine was significantly higher in pregnant females than in males, presumably due to the lower haematocrit in females. The fraction unbound in plasma (f) of etidocaine was low in control subjects (mean 0.057) and was not significantly different in pregnant women of 35 to 37 weeks gestation. A marked increase in f was observed in pregnant women during delivery (mean 0.264). This finding has potentially serious clinical implications because it is the unbound drug in blood which is pharmacologically important. Placental transfer of etidocaine was rapid and the cord/maternal venous blood concentration ratio at delivery (CM) was, with one exception, always less than unity (mean 0.342). Following epidural administration of etidocaine to pregnant women in labour, measurable concentrations of mono-dealkylated metabolites of etidocaine, PABX (2-N-propylamino-2′-butyroxylidide) and EABX (2-N-ethylamino-2′-butyroxylidide) were detectable in maternal blood within 5 min and cord blood within 30 min. The CM for PABX and EABX was 0.401 and 0.658 respectively. [ABSTRACT FROM AUTHOR]
- Published
- 1977
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20. Topical bupivacaine and etidocaine analgesia following fallopian tube banding.
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McKenzie, Ray, Phitayakorn, Preyaratt, Uy, Nonita, Chalasani, Jagadamba, Melnick, Brian, Kennedy, Roland, Vicinie, Albert, McKenzie, R, Phitayakorn, P, Uy, N T, Chalasani, J, Melnick, B M, Kennedy, R L, and Vicinie, A F 3rd
- Subjects
POSTOPERATIVE pain prevention ,ABDOMINAL pain ,AMIDES ,CLINICAL trials ,COMPARATIVE studies ,FALLOPIAN tubes ,LOCAL anesthesia ,RESEARCH methodology ,MEDICAL cooperation ,RESEARCH ,STATISTICAL sampling ,CUTANEOUS therapeutics ,TIME ,TUBAL sterilization ,EVALUATION research ,RANDOMIZED controlled trials ,BLIND experiment ,BUPIVACAINE ,PREVENTION - Abstract
Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 1989
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21. Sustained Release from Ionic-Gradient Liposomes Significantly Decreases ETIDOCAINE Cytotoxicity
- Author
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Lígia Nunes de Morais Ribeiro, Juliana Damasceno Oliveira, Verônica Muniz Couto, Eneida de Paula, Bruna Renata Casadei, Gustavo Henrique Rodrigues da Silva, and Elizabeth Ferreira Martinez
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Cell Survival ,Etidocaine ,Pharmaceutical Science ,02 engineering and technology ,030226 pharmacology & pharmacy ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Dynamic light scattering ,Phosphatidylcholine ,Zeta potential ,medicine ,Membrane fluidity ,Humans ,Pharmacology (medical) ,Anesthetics, Local ,Ions ,Pharmacology ,Liposome ,Vesicle ,Organic Chemistry ,Fibroblasts ,021001 nanoscience & nanotechnology ,Drug Liberation ,Cholesterol ,chemistry ,Delayed-Action Preparations ,Liposomes ,Drug delivery ,Phosphatidylcholines ,Biophysics ,Molecular Medicine ,0210 nano-technology ,Biotechnology ,medicine.drug - Abstract
Etidocaine (EDC) is a long lasting local anesthetic, which alleged toxicity has restricted its clinical use. Liposomes can prolong the analgesia time and reduce the toxicity of local anesthetics. Ionic gradient liposomes (IGL) have been proposed to increase the upload and prolong the drug release, from liposomes. First, a HPLC method for EDC quantification was validated. Then, large unilamellar vesicles composed of hydrogenated soy phosphatidylcholine:cholesterol with 250 mM (NH4)2SO4 - inside gradient - were prepared for the encapsulation of 0.5% EDC. Dynamic light scattering, nanotracking analysis, transmission electron microscopy and electron paramagnetic resonance were used to characterize: nanoparticles size, polydispersity, zeta potential, concentration, morphology and membrane fluidity. Release kinetics and in vitro cytotoxicity tests were also performed. IGLEDC showed average diameters of 172.3 ± 2.6 nm, low PDI (0.12 ± 0.01), mean particle concentration of 6.3 ± 0.5 × 1012/mL and negative zeta values (−10.2 ± 0.4 mV); parameters that remain stable during storage at 4°C. The formulation, with 40% encapsulation efficiency, induced the sustained release of EDC (ca. 24 h), while reducing its toxicity to human fibroblasts. A novel formulation is proposed for etidocaine that promotes sustained release and reduces its cytotoxicity. IGLEDC can come to be a tool to reintroduce etidocaine in clinical use.
- Published
- 2018
22. Patent Application Titled 'Composition For Treating Wounds And Other Dermatological Conditions' Published Online (USPTO 20200078330)
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Skin diseases ,Local anesthetics ,Chloroprocaine ,Benzocaine ,Bupivacaine ,Etidocaine ,Editors ,Mepivacaine ,Government ,Political science - Abstract
2020 APR 2 (VerticalNews) -- By a News Reporter-Staff News Editor at Politics & Government Week -- According to news reporting originating from Washington, D.C., by VerticalNews journalists, a patent [...]
- Published
- 2020
23. Patent Issued for Composite Containing Collagen And Elastin As A Dermal Expander And Tissue Filler (USPTO 10,583,218)
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Collagen -- Reports ,Skin care -- Reports ,Skin -- Reports ,Skin care products -- Intellectual property -- Reports ,Local anesthetics -- Reports ,Elastin -- Reports ,Chloroprocaine ,Benzocaine ,Bupivacaine ,Etidocaine ,Editors ,Mepivacaine ,Dyclonine ,Business ,Health - Abstract
2020 MAR 27 (NewsRx) -- By a News Reporter-Staff News Editor at Medical Patent Business Week -- From Alexandria, Virginia, NewsRx journalists report that a patent by the inventors Han, [...]
- Published
- 2020
24. Patent Issued for Formulations For The Treatment Of Pain (USPTO 10,576,047)
- Subjects
Patient compliance ,Local anesthetics ,Pain management ,Chloroprocaine ,Benzocaine ,Bupivacaine ,Etidocaine ,Reason ,Editors ,Mepivacaine ,Health - Abstract
2020 MAR 16 (NewsRx) -- By a News Reporter-Staff News Editor at AIDS Weekly -- According to news reporting originating from Alexandria, Virginia, by NewsRx journalists, a patent by the [...]
- Published
- 2020
25. Patent Issued for Rapid Action Insulin Formulations And Pharmaceutical Delivery Systems (USPTO 10,561,711)
- Subjects
Enflurane -- Intellectual property ,Type 2 diabetes ,Local anesthetics ,Insulin -- Intellectual property ,Chloroprocaine ,Benzocaine ,Etidocaine ,Editors ,Mepivacaine ,Business ,Health - Abstract
2020 MAR 6 (NewsRx) -- By a News Reporter-Staff News Editor at Medical Patent Business Week -- A patent by the inventors Berenson, Richard William (Waban, MA); Frank, Bruce (Indianapolis, [...]
- Published
- 2020
26. 'Drug Loaded Microspheres For Post-Operative Chronic Pain' in Patent Application Approval Process (USPTO 20200016081)
- Subjects
Chronic pain ,Local anesthetics ,Drug approval ,Chloroprocaine ,Disclosure of information ,Benzocaine ,Bupivacaine ,Etidocaine ,Editors ,Mepivacaine ,Pharmaceuticals and cosmetics industries - Abstract
2020 FEB 7 (NewsRx) -- By a News Reporter-Staff News Editor at Drug Week -- A patent application by the inventors Ohri, Rachit (Framingham, MA); Strichartz, Gary R. (Natick, MA); [...]
- Published
- 2020
27. 'Topical Preparation For Pain Relief' in Patent Application Approval Process (USPTO 20190374491)
- Subjects
Methyl salicylate ,Local anesthetics ,Pain management ,Chloroprocaine ,Benzocaine ,Bupivacaine ,Etidocaine ,Analgesia ,Editors ,Central nervous system ,Mepivacaine ,Health - Abstract
2019 DEC 30 (NewsRx) -- By a News Reporter-Staff News Editor at Pain & Central Nervous System Week -- A patent application by the inventor Greenspan, Michael Harvey (Dacula, GA), [...]
- Published
- 2019
28. Researchers Submit Patent Application, 'Anaesthetic Composition Comprising Ropivacaine, Prilocaine And Lidocaine', for Approval (USPTO 20190365730)
- Subjects
Chemical Abstracts Service -- Intellectual property ,Anesthetics ,Lidocaine ,Skin ,Local anesthetics ,Database industry -- Intellectual property ,Topical analgesics ,Prilocaine ,Bupivacaine ,Central nervous system agents ,Analgesics ,Etidocaine ,Editors ,Mepivacaine ,Database industry ,Health - Abstract
2019 DEC 23 (NewsRx) -- By a News Reporter-Staff News Editor at Cardiovascular Week -- From Washington, D.C., NewsRx journalists report that a patent application by the inventor Abdel-Rehim, Mohamed [...]
- Published
- 2019
29. Patent Issued for Pharmaceutical Compositions Comprising A Local Anaesthetic Such As Bupivacaine For Local Administration To The Mouth Or Throat (USPTO 10,493,068)
- Subjects
Local government ,Local anesthetics ,Pain management ,Benzocaine ,Bupivacaine ,Etidocaine ,Editors ,Business ,Health ,Health care industry - Abstract
2019 DEC 17 (NewsRx) -- By a News Reporter-Staff News Editor at Cancer Weekly -- Moberg Pharma AB (Bromma, Sweden) has been issued patent number 10,493,068, according to news reporting [...]
- Published
- 2019
30. Patent Issued for Drug Loaded Microspheres For Post-Operative Chronic Pain (USPTO 10,449,152)
- Subjects
Chronic pain ,Local anesthetics ,Medical equipment -- Intellectual property ,Chloroprocaine ,Technology ,Disclosure of information ,Benzocaine ,Bupivacaine ,Etidocaine ,Editors ,Mepivacaine ,Health ,Health care industry - Abstract
2019 NOV 10 (NewsRx) -- By a News Reporter-Staff News Editor at Medical Devices & Surgical Technology Week -- Covidien LP (Mansfield, Massachusetts, United States) has been issued patent number [...]
- Published
- 2019
31. Patent Application Titled 'Aspiration Device' Published Online (USPTO 20190247027)
- Subjects
Local anesthetics ,Stem cells ,Plerixafor ,Benzocaine ,Bupivacaine ,CAT scans ,Etidocaine ,Editors ,Health - Abstract
2019 SEP 5 (NewsRx) -- By a News Reporter-Staff News Editor at Blood Weekly -- According to news reporting originating from Washington, D.C., by NewsRx journalists, a patent application by [...]
- Published
- 2019
32. 'Formulations For The Treatment Of Pain' in Patent Application Approval Process (USPTO 20190247336)
- Subjects
Acorda Therapeutics Inc. -- Intellectual property ,Patient compliance ,Local anesthetics ,Pain management ,Biological products industry -- Intellectual property ,Chloroprocaine ,Benzocaine ,Bupivacaine ,Etidocaine ,Biotechnology ,Editors ,Biotechnology industry ,Pharmaceuticals and cosmetics industries - Abstract
2019 SEP 4 (NewsRx) -- By a News Reporter-Staff News Editor at Biotech Week -- A patent application by the inventor Maniar, Manoj (Fremont, CA), filed on August 20, 2018, [...]
- Published
- 2019
33. Patent Application Titled 'Composition For Treatment Of Infertility In A Female Subject' Published Online (USPTO 20190240338)
- Subjects
Infertility ,Amino acids -- Intellectual property ,Local anesthetics ,Hormones ,Bupivacaine ,Etidocaine ,Editors ,Health - Abstract
2019 AUG 26 (NewsRx) -- By a News Reporter-Staff News Editor at OBGYN & Reproduction Week -- According to news reporting originating from Washington, D.C., by NewsRx journalists, a patent [...]
- Published
- 2019
34. Patent Issued for Catheter Locking Solution Having Antimicrobial And Anticoagulation Properties (USPTO 10,350,334)
- Subjects
Becton, Dickinson and Co. -- Intellectual property ,Medical equipment industry -- Intellectual property ,Anticoagulants ,Local anesthetics ,Methicillin ,Chloroprocaine ,Benzocaine ,Bupivacaine ,Etidocaine ,Editors ,Dyclonine ,Health - Abstract
2019 JUL 29 (NewsRx) -- By a News Reporter-Staff News Editor at Hematology Week -- According to news reporting originating from Alexandria, Virginia, by NewsRx journalists, a patent by the [...]
- Published
- 2019
35. Patent Issued for Stimulation Electrode (USPTO 10,173,049)
- Subjects
Local anesthetics ,Bupivacaine ,Chloroprocaine ,Etidocaine ,Electrodes ,Editors ,Benzocaine ,Pharmaceuticals and cosmetics industries ,Health - Abstract
2019 JAN 25 (NewsRx) -- By a News Reporter-Staff News Editor at Genomics & Genetics Weekly -- According to news reporting originating from Alexandria, Virginia, by NewsRx journalists, a patent [...]
- Published
- 2019
36. Thirty years after the bupivacaine controversy: what have we learned?
- Author
-
Joanne Douglas and James Shannon
- Subjects
Bupivacaine ,Resuscitation ,Cardiotoxicity ,medicine.medical_specialty ,Etidocaine ,business.industry ,General Medicine ,Obstetric anesthesia ,Anesthesiology and Pain Medicine ,Anesthesia ,Anesthesiology ,Anesthetic ,medicine ,Childbirth ,business ,medicine.drug - Abstract
In October 1979, Albright wrote an editorial warning of the risks of cardiac toxicity due to bupivacaine and etidocaine. The editorial followed a report by Prentiss concerning a cardiac arrest in a patient receiving caudal anesthesia with etidocaine. In that case, cardiovascular collapse followed the rapid onset of convulsions after possible intravascular (iv) injection of etidocaine. To Albright’s knowledge, this was the sixth anecdotal case of sudden cardiovascular collapse following presumed iv injection of bupivacaine (0.5% or 0.75%) or etidocaine. He suggested that inadvertent iv administration of clinical doses of etidocaine and bupivacaine, in comparison with other local anesthetics (LAs), could result in almost simultaneous central nervous system and cardiovascular system toxicity without preceding hypoxia. Albright also noted that resuscitation was difficult, prolonged, and, in most situations, the outcome was poor. Subsequently, many additional cases of cardiovascular collapse were reported to the Federal Drug Administration (FDA) in the United States. A worrying number of these cases occurred in young previously healthy women who received epidural analgesia/anesthesia for childbirth. Albright’s editorial and the reports to the FDA prompted a letter to anesthesiologists in 1984 stating that 0.75% bupivacaine was no longer recommended for obstetric anesthesia because of the risk of cardiac arrest. Following this letter, the manufacturers of bupivacaine sent similar correspondence to Canadian anesthesiologists that caused considerable controversy and debate. In other countries, caution was urged in using 0.75% bupivacaine, although many anesthesiologists felt that the problem of cardiotoxicity was confined to the United States. In this issue of the Journal, Dillane and Finucane review the systemic toxicity of LAs, describing the mechanisms underlying central nervous system and cardiovascular toxicity associated with elevated plasma levels of LAs. They point out that systemic toxicity of LAs frequently results from inadvertent iv injection or from rapid absorption of the LA from the injection site with subsequent high plasma levels, and they suggest that there are benefits from the use of ultrasound during the performance of regional anesthesia. Ultrasound not only facilitates the identification of anatomical structures, hence avoiding iv injection, but also, it can facilitate more targeted administration of smaller volumes of LAs, thereby increasing the safety of regional anesthesia. What can we learn from this review article and other similar articles? First, the authors reiterate the history and the known facts regarding this potentially fatal complication. Second, by so doing, they encourage practicing anesthesiologists to examine their own practices and to consider whether LA administration is safe in light of the evidence presented. Although Albright and others implicated bupivacaine’s greater toxicity as the direct cause of cardiac arrest, this assessment was not universally accepted. As most drugs that are used for anesthesia are toxic if used in the wrong dose or wrong space, some anesthesiologists urged caution in blaming bupivacaine. These anesthesiologists questioned the anesthetic technique, as several of the obstetric cases presented to the FDA did not reflect what was considered good anesthetic practice at the time. In some of these cases, a large volume of a high concentration of LA was injected through the epidural J. Shannon, FCARCSI J. Douglas, MD (&) Department of Anesthesia, British Columbia’s Women’s Hospital and Health Centre and University of British Columbia, Room 1Q72, 4500 Oak Street, Vancouver, BC V6H 3N1, Canada e-mail: jdouglas@cw.bc.ca
- Published
- 2010
37. ETIDOCAINE AND LIDOCAINE IN OPHTHALMIC SURGERY: Short Communication
- Author
-
Arne Ellingsson and Henry Aasved
- Subjects
Adult ,medicine.medical_specialty ,Lidocaine ,Etidocaine ,medicine.medical_treatment ,Cataract Extraction ,Double-Blind Method ,medicine ,Humans ,Retrobulbar anesthesia ,Aged ,Ophthalmic surgery ,Clinical Trials as Topic ,Facial nerve block ,business.industry ,Nerve Block ,General Medicine ,Middle Aged ,Facial nerve ,Surgery ,Facial Nerve ,Ophthalmology ,Epinephrine ,Anesthesia ,Nerve block ,Acetanilides ,business ,Anesthesia, Local ,medicine.drug - Abstract
A double-blind study has been made comparing etidocaine 1% (Duranest®) and lidocaine 2% (Xylocain®). The investigation comprised 92 patients with senile cataract, operated under retrobulbar anesthesia and facial nerve block. During the normal interval between the injection and the operation, lidocaine seemed to be more effective than etidocaine, both as an analgetic and kinetic agent, while etidocaine had a longer analgetic effect. The relative high adrenaline (epinephrine) content in lidocaine 2% is discussed.
- Published
- 2009
38. Physicochemical Modification of Lidocaine Uptake in Rat Lung Tissue
- Author
-
E. Nilsson, R. C. C. Andersson, Å. Ryrfeldt, and Claes Post
- Subjects
Pharmacology ,Bupivacaine ,Lung ,Lidocaine ,Chemistry ,Etidocaine ,Nortriptyline ,Hydrogen-Ion Concentration ,Toxicology ,Rats ,Perfusion ,Membrane ,medicine.anatomical_structure ,Bolus (medicine) ,medicine ,Animals ,Female ,Lung tissue ,medicine.drug - Abstract
The uptake of lidocaine, methyllidocaine, bupivacaine, etidocaine was studied in rat lung slices at different pH-values. The accumulation of the quaternary analogue, methyllidocaine, was not changed in the pH interval 7.0--8.0. The uptake of the three other substances was about 3--4 times lower at pH 7.0 than at pH 8.0. The rank order of distribution at a fixed cation/base ratio was bupivacaine greater than etidocaine greater than lidocaine. Interactions between lidocaine and other substances were studied in lung slices and in isolated perfused lungs. Bupivacaine and nortriptyline counteracted the accumulation of 14C-lidocaine in lung slices in a dose-dependent manner. Nortriptyline was more effective than bupivacaine. In isolated perfused lung, bolus injections of nortriptyline and lidocaine rapidly displaced 14C-lidocaine from the tissue. In this study we suggest that the base form of local anaesthetics accumulate in the lung tissue, while the cationic form binds to accessible binding sites in the cell membranes.
- Published
- 2009
39. Studies on the Pharmacokinetic Function of the Lung with Special Reference to Lidocaine
- Author
-
Claes Post
- Subjects
Pharmacology ,Lung ,Lidocaine ,Swine ,Chemistry ,Smoking ,Nortriptyline ,Hydrogen-Ion Concentration ,Toxicology ,Bupivacaine ,Models, Biological ,Perfusion ,Kinetics ,medicine.anatomical_structure ,Pharmacokinetics ,Anesthesia ,medicine ,Animals ,Etidocaine ,Humans ,Female ,medicine.drug - Published
- 2009
40. Preferential location of lidocaine and etidocaine in lecithin bilayers as determined by EPR, fluorescence and 2H NMR
- Author
-
Shirley Schreier, Eneida de Paula, Harold C. Jarrell, and Leonardo Fernandes Fraceto
- Subjects
Magnetic Resonance Spectroscopy ,Stereochemistry ,Lipid Bilayers ,Biophysics ,Biochemistry ,Fluorescence ,law.invention ,chemistry.chemical_compound ,law ,Phosphatidylcholine ,Lecithins ,Animals ,Moiety ,Anesthetics, Local ,Electron paramagnetic resonance ,Fluorescent Dyes ,Liposome ,Bilayer ,Organic Chemistry ,Electron Spin Resonance Spectroscopy ,Lidocaine ,Nuclear magnetic resonance spectroscopy ,chemistry ,Liposomes ,Proton NMR ,Etidocaine ,Spin Labels ,lipids (amino acids, peptides, and proteins) ,Stearic acid - Abstract
We have examined the effect of the uncharged species of lidocaine (LDC) and etidocaine (EDC) on the acyl chain moiety of egg phosphatidylcholine liposomes. Changes in membrane organization caused by both anesthetics were detected through the use of EPR spin labels (5, 7 and 12 doxyl stearic acid methyl ester) or fluorescence probes (4, 6, 10, 16 pyrene-fatty acids). The disturbance caused by the LA was greater when the probes were inserted in more external positions of the acyl chain and decreased towards the hydrophobic core of the membrane. The results indicate a preferential insertion of LDC at the polar interface of the bilayer and in the first half of the acyl chain, for EDC. Additionally, (2)H NMR spectra of multilamellar liposomes composed by acyl chain-perdeutero DMPC and EPC (1:4 mol%) allowed the determination of the segmental order (S(mol)) and dynamics (T(1)) of the acyl chain region. In accordance to the fluorescence and EPR results, changes in molecular orientation and dynamics are more prominent if the LA preferential location is more superficial, as for LDC while EDC seems to organize the acyl chain region between carbons 2-8, which is indicative of its positioning. We propose that the preferential location of LDC and EDC inside the bilayers creates a "transient site", which is related to the anesthetic potency since it could modulate the access of these molecules to their binding site(s) in the voltage-gated sodium channel.
- Published
- 2008
41. Liquid chromatography–electrospray mass spectrometry determination of free and total concentrations of ropivacaine in human plasma
- Author
-
Franck Barnay, Christophe Dadure, Jean Claude Mathieu-Daudé, Dominique Hillaire-Buys, Olivier Mathieu, and Françoise Bressolle
- Subjects
Spectrometry, Mass, Electrospray Ionization ,Electrospray ,Etidocaine ,Electrospray ionization ,Clinical Biochemistry ,Analytical chemistry ,Trimethylamine ,Mass spectrometry ,Sensitivity and Specificity ,Biochemistry ,Analytical Chemistry ,chemistry.chemical_compound ,Drug Stability ,medicine ,Ammonium formate ,Humans ,Ropivacaine ,Psoas Muscles ,Chromatography ,Chemistry ,Reproducibility of Results ,Nerve Block ,Cell Biology ,General Medicine ,Amides ,Dialysis ,Quantitative analysis (chemistry) ,Anesthesia, Local ,Chromatography, Liquid ,medicine.drug - Abstract
A specific and sensitive liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method was developed for the determination of free and total ropivacaine in human plasma. The work-up procedure involved a simple precipitation of plasma proteins with methanol. Etidocaine served as the internal standard. After microscale equilibrium-dialysis, measurement of free ropivacaine levels was performed after direct injection of the dialysate into the chromatograph. The system used a Zorbax eclipse XD8 C8 analytical column packed with 5 microm diameter particles as the stationary phase. The mobile phase consisted of a 15-min gradient (mobile phase A: 0.05% (v/v) trimethylamine in acetonitrile, mobile phase B: 2mM ammonium formate buffer (pH 3)). Mass spectrometric data were acquired in single ion monitoring mode at m/z 275 for ropivacaine and m/z 277 for etidocaine. The drug/internal standard peak area ratios (plasma) or peak areas (dialysate) were linked via a quadratic relationship to concentrations. Precision ranged from 1 to 7.6% accuracy was between 92.6 and 109%. The lower limits of quantitation were 1 microg/l in plasma and 2 microg/l in the dialysate. This method was found suitable for the analysis of plasma samples collected during a clinical trial performed in 30 infants undergoing epidural anaesthesia or continuous psoas compartment block.
- Published
- 2006
42. Lokalan�sthetika
- Author
-
A Borgeat and A Dullenkopf
- Subjects
Bupivacaine ,Tertiary amine ,Etidocaine ,Ropivacaine ,business.industry ,Local anesthetic ,medicine.drug_class ,Sodium channel ,General Medicine ,Pharmacology ,Anesthesiology and Pain Medicine ,Mechanism of action ,Anesthesia ,Lipophilicity ,medicine ,medicine.symptom ,business ,medicine.drug - Abstract
Local anesthetics provoke reversible blockade of nerves by interaction with sodium channels in membranes of nerves. The uncharged molecular configuration of the local anesthetic penetrates the membrane from the outside and the charged configuration then interacts with the sodium channel from the inside. The potency of a local anesthetic is determined mainly by lipid solubility, the time of onset by the pK(a) of the substance and the duration of action by protein binding. Local anesthetic molecules consist of a hydrophilic tertiary amine and a lipophilic aromatic system combined by an ester or amide linkage. Local anesthetics may therefore be classified as aminoester or aminoamide compounds. Aminoesters are hydrolysed by plasmacholinesterase whereas aminoamides undergo metabolisation in the liver. Aminoamides cause fewer allergic reactions. Local anesthetics show dose-dependent CNS and cardiac toxicity. Reports of toxicity, mainly involving bupivacaine and etidocaine initiated the development of ropivacaine which is the first aminoamide marketed as a pure S-enantiomer. Recently introduced was levo-bupivacaine, the S-enantiomer of bupivacaine.
- Published
- 2003
43. Cardiac toxicity of local anesthetics in the intact isolated heart model
- Author
-
James E. Heavner
- Subjects
Potassium Channels ,Swine ,Etidocaine ,medicine.drug_class ,In Vitro Techniques ,Electrocardiography ,Heart Conduction System ,medicine ,Animals ,Ropivacaine ,Anesthetics, Local ,Bupivacaine ,Cardiotoxicity ,medicine.diagnostic_test ,business.industry ,Local anesthetic ,Lidocaine ,Arrhythmias, Cardiac ,Stereoisomerism ,Sudden cardiac arrest ,Isolated heart ,General Medicine ,Amides ,Rats ,Anesthesiology and Pain Medicine ,Anesthesia ,Calcium Channels ,Rabbits ,medicine.symptom ,business ,medicine.drug - Abstract
An editorial in 1979 by George Albright about sudden cardiac arrest after regional anesthesia spawned an era of intense research focusing on what local anesthetics do to the heart and how they do it. The ultimate goal of the research was to bring to the clinician long-acting local anesthetics that are less cardiotoxic than ones available before 1979, bupivacaine and etidocaine, in particular. In this article, I will review results of studies of local anesthetic cardiotoxicity using the intact mammalian heart in vitro published after the Albright editorial through 2001.
- Published
- 2002
44. Block of voltage-operated sodium channels by 2,6-dimethylphenol, a structural analogue of lidocaine's aromatic tail
- Author
-
Reinhard Dengler, Martin Leuwer, Jeffrey K Aronson, Sarah Merken, Gertrud Haeseler, and Johannes Bufler
- Subjects
Pharmacology ,Etidocaine ,Chemistry ,Sodium ,Sodium channel ,chemistry.chemical_element ,Skeletal muscle ,Dissociation constant ,Electrophysiology ,Sodium channel blocker ,medicine.anatomical_structure ,Mechanism of action ,Anesthesia ,medicine ,Biophysics ,medicine.symptom ,medicine.drug - Abstract
1. The structural features that determine the state-dependent interaction of local anaesthetics with voltage-operated sodium channels are still a matter of debate. We have studied the blockade of sodium channels by 2,6-dimethylphenol, a phenol derivative which resembles the aromatic tail of lidocaine, etidocaine, and bupivacaine. 2. The effects of 2,6-dimethylphenol were studied on heterologously (HEK 293) expressed rat neuronal (rat brain IIA) and human skeletal muscle (hSkM1) sodium channels using whole-cell voltage-clamp experiments. 3. 2,6-Dimethylphenol was effective in blocking whole-cell sodium inward currents. Its potency was comparable to the potency of lidocaine previously obtained with similar protocols by others. The IC(50) at -70 mV holding potential was 150 and 187 microM for the skeletal muscle and the neuronal isoform, respectively. In both isoforms, the blocking potency increased with the fraction of inactivated channels at depolarized holding potentials. However, the block achieved at -70 mV with respect to -150 mV holding potential was significantly higher only in the skeletal muscle isoform. The estimated dissociation constant K(d) from the inactivated state was 25 microM and 28 microM in the skeletal muscle and the neuronal isoform, respectively. The kinetics of drug equilibration between resting and inactivated channel states were about 10 fold faster compared with lidocaine. 4. Our results show that the blockade induced by 2,6-dimethylphenol retains voltage-dependency, a typical feature of lidocaine-like local anaesthetics. This is consistent with the hypothesis that the 'aromatic tail' determines the state-dependent interaction of local anaesthetics with the sodium channel.
- Published
- 2002
45. Role of Amino Acid Residues in Transmembrane Segments IS6 and IIS6 of the Na+ Channel α Subunit in Voltage-dependent Gating and Drug Block
- Author
-
Caroline Pate, Jancy C. McPhee, Todd Scheuer, Diane Idsvoog, Vladimir Yarov-Yarovoy, and William A. Catterall
- Subjects
Drug ,Etidocaine ,Xenopus ,media_common.quotation_subject ,Nerve Tissue Proteins ,medicine.disease_cause ,Biochemistry ,Sodium Channels ,medicine ,Animals ,Point Mutation ,Amino Acids ,Anesthetics, Local ,Receptor ,Molecular Biology ,media_common ,Mutation ,Α subunit ,NAV1.2 Voltage-Gated Sodium Channel ,Chemistry ,Mutagenesis ,Brain ,Cell Biology ,Transmembrane protein ,Rats ,Mutagenesis, Site-Directed ,Biophysics ,Anticonvulsants ,Ion Channel Gating ,Intracellular ,medicine.drug - Abstract
Alanine-scanning mutagenesis of transmembrane segments IS6 and IIS6 of the rat brain Na(v)1.2 channel alpha subunit identified mutations N418A in IS6 and L975A in IIS6 as causing strong positive shifts in the voltage dependence of activation. In contrast, mutations V424A in IS6 and L983A in IIS6 caused strong negative shifts. Most IS6 mutations opposed inactivation from closed states, but most IIS6 mutations favored such inactivation. Mutations L421C and L983A near the intracellular ends of IS6 and IIS6, respectively, exhibited significant sustained Na(+) currents at the end of 30-ms depolarizations, indicating a role for these residues in Na(+) channel fast inactivation. These residues, in combination with residues at the intracellular end of IVS6, are well situated to form an inactivation gate receptor. Mutation I409A in IS6 reduced the affinity of the local anesthetic etidocaine for the inactivated state by 6-fold, and mutations I409A and N418A reduced use-dependent block by etidocaine. No IS6 or IIS6 mutations studied affected inactivated-state affinity or use-dependent block by the neuroprotective drug sipatrigine (compound 619C89). These results suggest that the local anesthetic receptor site is formed primarily by residues in segments IIIS6 and IVS6 with the contribution of a single amino acid in segment IS6.
- Published
- 2002
46. Spectrophotometric determination of etidocaine in pharmaceutical (dental) formulation
- Author
-
Nelson Silva and Elfrides Eva Scherman Schapoval
- Subjects
Sodium Acetate ,Etidocaine ,Calibration curve ,Anesthesia, Dental ,Clinical Biochemistry ,Analytical chemistry ,Pharmaceutical Science ,Buffers ,Bromcresol Green ,Dosage form ,Analytical Chemistry ,Absorbance ,chemistry.chemical_compound ,Spectrophotometry ,Drug Discovery ,medicine ,Anesthetics, Local ,Spectroscopy ,Bromocresol green ,Chromatography ,Chloroform ,medicine.diagnostic_test ,Extraction (chemistry) ,Reproducibility of Results ,Pharmaceutical Preparations ,chemistry ,medicine.drug - Abstract
A spectrophotometric method was developed for the determination of etidocaine hydrochloride (EH) in injectable pharmaceutical preparation. The proposal of this work was to develop a rapid, simple, inexpensive, precise and accurate visible spectrophotometric method. The method is based on the formation of the ion-pair complex by the EH reaction with bromocresol green in the pH 4.6 which after chloroform extraction gives a yellow color that in basic medium change to blue color and exhibits a maximum absorbance at 625 nm. The calibration graph was linear over the range 2.0–6.0 μg ml −1 EH calculated on the final yellow solution. The R.S.D. of the slope of the four lines was 0.73%. This method can be applied to injectable pharmaceutical preparation dosage studied.
- Published
- 2002
47. From Cocaine to Ropivacaine: The History of Local Anesthetic Drugs
- Author
-
Alain Borgeat, Yvan A. Ruetsch, and Thomas Boni
- Subjects
Tetracaine ,Etidocaine ,medicine.drug_class ,Mepivacaine ,Pharmacology ,Procaine ,Cocaine ,Drug Discovery ,Animals ,Humans ,Medicine ,Ropivacaine ,Local anesthesia ,Anesthetics, Local ,business.industry ,Local anesthetic ,History, 19th Century ,General Medicine ,History, 20th Century ,Amides ,Bupivacaine ,Europe ,Anesthesia ,North America ,business ,medicine.drug ,Chloroprocaine - Abstract
In 1850, about three centuries after the conquest of Peru by Pizzaro, the Austrian von Scherzer brought a sufficient quantum of coca leaves to Europe to permit the isolation of cocaine. As suggested by his friend Sigmund Freud, descriptions of the properties of the coca prompted the Austrian Koller to perform in 1884 the first clinical operation under local anesthesia, by administration of cocaine on the eye. The use of cocaine for local and regional anesthesia rapidly spread throughout Europe and America. The toxic effects of cocaine were soon identified resulting in many deaths among both patients and addicted medical staff. Local anesthesia was in a profound crisis until the development of modern organic chemistry which led to the synthesis of pure cocaine in 1891. New amino ester local anesthetics were synthesized between 1891 and 1930, such as tropocaine, eucaine, holocaine, orthoform, benzocaine, and tetracaine. In addition, amino amide local anesthetics were prepared between 1898 and 1972 including nirvaquine, procaine, chloroprocaine, cinchocaine, lidocaine, mepivacaine, prilocaine, efocaine, bupivacaine, etidocaine, and articaine. All of these drugs were ostensibly less toxic than cocaine, but they had differing amounts of central nervous system (CNS) and cardiovascular (CV) toxicity. Bupivacaine is of special interest because of its long duration of action and history of clinical application. Synthesized in 1957, the introduction of bupivacaine on the market in 1965 paralleled the progressive and cumulative reports of CNS and CV toxicity, leading to the restriction of its use and the identification of a special therapy-resistant CV toxicity. Numerous experimental studies were conducted to identify the fine cellular mechanism of this toxicity, which refines our understanding of the action of local anesthetics. The identification of optically active isomers of the mepivacaine family led to the selection of ropivacaine, a pure S-(-) enantiomer, whose toxicology was selectively and extensively studied before its introduction on the market in 1996. During the rapid and extensive use of ropivacaine in the clinic, unwanted side-effects have been found to be very limited.
- Published
- 2001
48. Molecular Determinants of Voltage-dependent Gating and Binding of Pore-blocking Drugs in Transmembrane Segment IIIS6 of the Na+ Channel α Subunit
- Author
-
William A. Catterall, Jacob Brown, Vladimir Yarov-Yarovoy, Todd Scheuer, Jeffrey J. Clare, and Elizabeth M. Sharp
- Subjects
Patch-Clamp Techniques ,Etidocaine ,Stereochemistry ,Plasma protein binding ,Lamotrigine ,Biochemistry ,Piperazines ,Sodium Channels ,Xenopus laevis ,Protein structure ,medicine ,Animals ,Point Mutation ,Patch clamp ,Anesthetics, Local ,Binding site ,Molecular Biology ,Alanine ,Binding Sites ,Triazines ,Chemistry ,Point mutation ,Brain ,Membrane Proteins ,Cell Biology ,Protein Structure, Tertiary ,Rats ,Electrophysiology ,Transmembrane domain ,Pyrimidines ,Amino Acid Substitution ,Oocytes ,Thermodynamics ,Anticonvulsants ,Ion Channel Gating ,Protein Binding ,Sodium Channel Blockers ,medicine.drug - Abstract
Mutations of amino acid residues in the inner two-thirds of the S6 segment in domain III of the rat brain type IIA Na(+) channel (G1460A to I1473A) caused periodic positive and negative shifts in the voltage dependence of activation, consistent with an alpha-helix having one face on which mutations to alanine oppose activation. Mutations in the outer one-third of the IIIS6 segment all favored activation. Mutations in the inner half of IIIS6 had strong effects on the voltage dependence of inactivation from closed states without effect on open-state inactivation. Only three mutations had strong effects on block by local anesthetics and anticonvulsants. Mutations L1465A and I1469A decreased affinity of inactivated Na(+) channels up to 8-fold for the anticonvulsant lamotrigine and its congeners 227c89, 4030w92, and 619c89 as well as for the local anesthetic etidocaine. N1466A decreased affinity of inactivated Na(+) channels for the anticonvulsant 4030w92 and etidocaine by 3- and 8-fold, respectively, but had no effect on affinity of the other tested compounds. Leu-1465, Asn-1466, and Ile-1469 are located on one side of the IIIS6 helix, and mutation of each caused a positive shift in the voltage dependence of activation. Evidently, these amino acid residues face the lumen of the pore, contribute to formation of the high-affinity receptor site for pore-blocking drugs, and are involved in voltage-dependent activation and coupling to closed-state inactivation.
- Published
- 2001
49. Continuous mixed venous oxygen saturation, not mean blood pressure, is associated with early bupivacaine cardiotoxicity in dogs
- Author
-
Kim, Jin-Tae, Rhee, Ka-Young, Bahk, Jae-Hyon, Do, Sang-Hwan, Lim, Young-Jin, Ko, Hong, and Lee, Kook-Hyun
- Published
- 2003
- Full Text
- View/download PDF
50. Determination of Lidocaine in Hair of Drug Fatalities by Headspace Solid-Phase Microextraction
- Author
-
Fritz Pragst and Frank Sporkert
- Subjects
Adult ,Male ,Narcotics ,Adolescent ,Lidocaine ,Etidocaine ,medicine.drug_class ,Health, Toxicology and Mutagenesis ,Toxicology ,Solid-phase microextraction ,Sensitivity and Specificity ,Analytical Chemistry ,chemistry.chemical_compound ,Cocaine ,medicine ,Humans ,Vasoconstrictor Agents ,Environmental Chemistry ,Solid phase extraction ,Anesthetics, Local ,Chemical Health and Safety ,Chromatography ,Chemistry ,Local anesthetic ,Codeine ,Forensic Medicine ,Dihydrocodeine ,Heroin ,Calibration ,Benzoylecgonine ,Female ,Drug Overdose ,Drug Contamination ,Hair ,medicine.drug - Abstract
The local anesthetic lidocaine was determined in hair by hydrolysis of the samples with 4% NaOH in the presence of excessive Na2SO4 and subsequent headspace solid-phase microextraction with a 65-pro Carbowax/divinylbenzene fiber, and gas chromatography-mass spectrometry measurement with etidocaine as the internal standard. The calibration curve was linear between 0.1 and 1000 ng/mg. The detection and quantitation limits were 0.1 and 0.4 ng/mg, respectively. The method was applied to hair samples of 49 drug fatalities, and positive results were obtained in 32 cases with lidocaine concentrations between 0.4 and 400 ng/mg and 675 ng/mg in one extreme case. For comparison, morphine, 6-acetylmorphine, codeine, dihydrocodeine, methadone, cocaine, and benzoylecgonine were also determined by usual methods. From segmental investigations in four of the cases and from comparison with the hair concentrations of the other drugs, it follows that lidocaine was consumed for a longer period of time as an adulterant of cocaine and heroin preparations. case of death after repeated use of this anesthetic during episodes of self mutilation. Such high concentrations suggest a very efficient deposition of this drug into hair.
- Published
- 2000
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