Pestel, G; Sprenger, H; Rothhammer, A
Atypical cholinesterase prolongs the duration of neuromuscular blocking drugs such as succinylcholine and mivacurium. Measuring the dibucaine number identifies patients who are at risk. This study shows the frequency distribution of dibucaine numbers routinely measured and discusses avoidable clinical problems and economic implications. Dibucaine numbers were measured on a Hitachi 917-analyzer and all dibucaine numbers recorded over a period of 4 years were taken into consideration. Repeat observations were excluded. A total of 24,830 dibucaine numbers were analysed and numbers below 30 were found in 0.07% ( n=18) giving an incidence of 1:1,400. Dibucaine numbers from 30 to 70 were found in 1.23% ( n=306). On the basis of identification of the Dibucaine numbers we could avoid the administration of succinylcholine or mivacurium resulting in a cost reduction of 12,280 Euro offset against the total laboratory costs amounting to 10,470 Euro. An incidence of 1:1,400 of dibucaine numbers below 30 is higher than documented in the literature. Therefore, routine measurement of dibucaine number is a cost-effective method of identifying patients at increased risk of prolonged neuromuscular blockade due to atypical cholinesterase.
W Christopher Risher
Full Text Available Spreading depolarizations that occur in patients with malignant stroke, subarachnoid/intracranial hemorrhage, and traumatic brain injury are known to facilitate neuronal damage in metabolically compromised brain tissue. The dramatic failure of brain ion homeostasis caused by propagating spreading depolarizations results in neuronal and astroglial swelling. In essence, swelling is the initial response and a sign of the acute neuronal injury that follows if energy deprivation is maintained. Choosing spreading depolarizations as a target for therapeutic intervention, we have used human brain slices and in vivo real-time two-photon laser scanning microscopy in the mouse neocortex to study potentially useful therapeutics against spreading depolarization-induced injury.We have shown that anoxic or terminal depolarization, a spreading depolarization wave ignited in the ischemic core where neurons cannot repolarize, can be evoked in human slices from pediatric brains during simulated ischemia induced by oxygen/glucose deprivation or by exposure to ouabain. Changes in light transmittance (LT tracked terminal depolarization in time and space. Though spreading depolarizations are notoriously difficult to block, terminal depolarization onset was delayed by dibucaine, a local amide anesthetic and sodium channel blocker. Remarkably, the occurrence of ouabain-induced terminal depolarization was delayed at a concentration of 1 µM that preserves synaptic function. Moreover, in vivo two-photon imaging in the penumbra revealed that, though spreading depolarizations did still occur, spreading depolarization-induced dendritic injury was inhibited by dibucaine administered intravenously at 2.5 mg/kg in a mouse stroke model.Dibucaine mitigated the effects of spreading depolarization at a concentration that could be well-tolerated therapeutically. Hence, dibucaine is a promising candidate to protect the brain from ischemic injury with an approach that does not rely on
Full Text Available ine (INN) D02220 ... Dibucaine hydrochloride (JP17/USP) Neuropsychiatric agent ... DG02030 ... Anesthetics ... DG01675 ... Local anesthetic... ... DG01673 ... Amide type local anesthetic ... DG01675 ... Local anesthetic ... DG01673 ... Amide type local anesthetic... ATC code: C05AD04 D04AB02 N01BB06 S01HA06 S02DA04 Anesthetic (loc
... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Local anesthetic active ingredients. 346.10 Section 346.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... ingredient: (a) Benzocaine 5 to 20 percent. (b) Benzyl alcohol 1 to 4 percent. (c) Dibucaine 0.25 to 1...
妹尾, 洋; 服部, 秀樹; 熊澤, 武志; 鈴木, 修; 木村, 美智子; 山田, 高路
Tricyclic antidepressants and local anesthetics were detected by gas chromatography (GC)-surface ionization detection (SID), which has been reported to be very sensitive and specific to tertiary amines. The detection limit in an injected volume was 5-10 pg for amitriptyline, imipramine, trimipramine, chlorimipramine, lidocaine, mepivacaine and bupivacaine, and 100-200 pg for procaine, benoxinate and dibucaine. When compared with the GC-nitrogen-phosphorus detection (NPD), the GC-SID sensitivi...
Masuda, R; Yokoyama, K; Inoue, T
We studied the spread of spinal anesthesia with 3 different hyperbaric solutions commercially available in Japan. Percamin-S [0.3% dibucaine in 5% hyperbaric saline] (P), Neo-Percamin.S [0.24% dibucaine with 0.12% T-caine in 9.5% glucose] (N) and 0.5% Tetcaine [tetracaine] in 10% glucose (T) were studied. Two ml of each solution was administered intrathecally using a 25 gauge Quincke needle. Patients (n = 90) were allocated to one of 9 groups receiving 2 ml of P, N or T at L 2-3, L 3-4 or L 4-5 interspace. Both N and T produced significantly higher spread of analgesia than P at any of L 3-4 and L 4-5 interspaces. P and N have the same specific gravity, even though significant differences were found in spread of segmental analgesia. Local anesthesic agents and solvent solutions themselves are considered to influence the spread of spinal anesthesia as the specific gravity of hyperbaric solution does.
Small unilamellar vesicles from egg phosphatidylcholine in NaCl solutions were exposed to some amphiphilic pharmaca. The aromatic drugs (chlorpromazine, dibucaine, tetracaine, imipramine and propranolol) were in their cationic form of the amines. By 1 H- and 31 P-NMR the membrane signals were observed. In particular, the N-methyl choline proton signals were followed upon drug addition. The intrinsic chemical shift difference (0.02 ppm) between the inner (upfield) and outer choline signals was influenced by the drug concentration. Packing properties of the lipid head groups and ring current shift probably contributed. At very high drug concentration, the vesicles are destroyed. A transformation into a micellar state with a high sample viscosity took place in a narrow concentration range of drug. The anion effects of Cl - were studied from the 35 Cl-NMR linewidth at 9.8 and 39.1 MHz. A continuous increase in the signal linewidth followed upon drug addition to the vesicles. Only chlorpromazine produced a broadening in the absence of vesicles (NaCl blank). The linewidth reflected a critical micelle concentration of this drug around 7 mM in 0.1 M NaCl. The 35 Cl-NMR experiments demonstrated the existence of an anionic counterion effect. This phenomenon should be accounted for when quantitatively analysing drug-membrane interactions in electrostatic terms. (Auth.)
Ma, Pengju; Li, Ting; Xing, Huaixin; Wang, Suzhen; Sun, Yingui; Sheng, Xiugui; Wang, Kaiguo
There is a compelling need for prolonged local anesthetic that would be used for analgesia with a single administration. However, due to the low molecular weight of local anesthetics (LA) (lidocaine, bupivacaine, procaine, dibucaine, etc), they present fast systemic absorption. The aim of the present study was to develop and evaluate bupivacaine lipid-polymer hybrid nanoparticles (BVC LPNs), and compared with BVC loaded PLGA nanoparticles (BVC NPs). Their morphology, particle size, zeta potential and drug loading capacity were evaluated. In vitro release study, stability and cytotoxicity were studied. In vivo evaluation of anesthetic effects was performed on animal models. A facile nanoprecipitation and self-assembly method was optimized to obtain BVC LPNs, composed of PLGA, lecithin and DSPE-PEG 2000 , of ∼175nm particle size. Compared to BVC NPs, BVC LPNs exhibited prolonged in vitro release in phosphate-buffered saline (pH=7.4). Further, BVC LPNs displayed enhanced in vitro stability in 10% FBS and lower cytotoxicity (the concentration of BVC ranging from 1.0μM to 20μM). In addition, BVC LPNs exhibited significantly prolonged analgesic duration. These results demonstrate that the LPNs could function as promising drug delivery system for overcoming the drawbacks of poor stability and rapid drug leakage, and prolonging the anesthetic effect with slight toxicity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Warshaw, Erin M; Belsito, Donald V; Taylor, James S; Sasseville, Denis; DeKoven, Joel G; Zirwas, Matthew J; Fransway, Anthony F; Mathias, C G Toby; Zug, Kathryn A; DeLeo, Vincent A; Fowler, Joseph F; Marks, James G; Pratt, Melanie D; Storrs, Frances J; Maibach, Howard I
Patch testing is an important diagnostic tool for determination of substances responsible for allergic contact dermatitis. This study reports the North American Contact Dermatitis Group (NACDG) patch testing results from January 1, 2009, to December 31, 2010. At 12 centers in North America, patients were tested in a standardized manner with a screening series of 70 allergens. Data were manually verified and entered into a central database. Descriptive frequencies were calculated, and trends were analyzed using χ2 statistics. A total of 4308 patients were tested. Of these, 2614 (60.7%) had at least 1 positive reaction, and 2284 (46.3%) were ultimately determined to have a primary diagnosis of allergic contact dermatitis. Four hundred twenty-seven (9.9%) patients had occupationally related skin disease. There were 6855 positive allergic reactions. As compared with the previous reporting period (2007-2008), the positive reaction rates statistically decreased for 20 allergens (nickel, neomycin, Myroxylon pereirae, cobalt, formaldehyde, quaternium 15, methydibromoglutaronitrile/phenoxyethanol, methylchlorisothiazolinone/methylisothiazolinone, potassium dichromate, diazolidinyl urea, propolis, dimethylol dimethylhydantoin, 2-bromo-2-nitro-1,3-propanediol, methyl methacrylate, ethyl acrylate, glyceryl thioglycolate, dibucaine, amidoamine, clobetasol, and dimethyloldihydroxyethyleneurea; P < 0.05) and statistically increased for 4 allergens (fragrance mix II, iodopropynyl butylcarbamate, propylene glycol, and benzocaine; P < 0.05). Approximately one quarter of tested patients had at least 1 relevant allergic reaction to a non-NACDG allergen. Hypothetically, approximately one quarter of reactions detected by NACDG allergens would have been missed by TRUE TEST (SmartPractice Denmark, Hillerød, Denmark). These results affirm the value of patch testing with many allergens.
Mashimo, T.; Abe, K.; Yoshiya, I.
The effects of local anesthetics and a divalent cation, Ca2+, on the function of rhodopsin were estimated from the measurements of light-induced proton uptake. The light-induced proton uptake by rhodopsin in the rod outer segment disk membrane was enhanced at lower pH (4) but depressed at higher pHs (6 to 8) by the tertiary amine local anesthetics lidocaine, bupivacaine, tetracaine, and dibucaine. The order of local anesthetic-induced depression of the proton uptake followed that of their clinical anesthetic potencies. The depression of the proton uptake versus the concentration of the uncharged form of local anesthetic nearly describes the same curve for small and large dose of added anesthetic. Furthermore, a neutral local anesthetic, benzocaine, depressed the proton uptake at all pHs between 4 and 7. These results indicate that the depression of the proton uptake is due to the effect of only the uncharged form. It is hypothesized that the uncharged form of local anesthetics interacts hydrophobically with the rhodopsin in the disk membrane. The dual effect of local anesthetics on the proton uptake, on the other hand, suggests that the activation of the function of rhodopsin may be caused by the charged form. There was no significant change in the light-induced proton uptake by rhodopsin when 1 mM of Ca2+ was introduced into the disk membrane at varying pHs in the absence or presence of local anesthetics. This fact indicates that Ca2+ ion does not influence the diprotonating process of metarhodopsin; neither does it interfere with the local anesthetic-induced changes in the rhodopsin molecule.
Full Text Available Butyrylcholinesterase (BChE activity assay and inhibitor phenotyping can help to identify patients at risk of prolonged paralysis following the administration of neuromuscular blocking agents. The assay plays an important role in clinical chemistry as a good diagnostic marker for intoxication with pesticides and nerve agents. Furthermore, the assay is also commonly used for in vitro characterization of cholinesterases, their toxins and drugs. There is still lack of standardized procedure for measurement of BChE activity and many laboratories use different substrates at various concentrations. The purpose of this study was to validate the BChE activity assay to determine the best dilution of human serum and the most optimal concentration of substrates and inhibitors. Serum BChE activity was measured using modified Ellman's method applicable for a microplate reader. We present our experience and new insights into the protocol for high-throughput routine assays of human plasma cholinesterase activities adapted to a microplate reader. During our routine assays used for the determination of BChE activity, we have observed that serum dilution factor influences the results obtained. We show that a 400-fold dilution of serum and 5mM S-butyrylthiocholine iodide can be successfully used for the accurate measurement of BChE activity in human serum. We also discuss usage of various concentrations of dibucaine and fluoride in BChE phenotyping. This study indicates that some factors of such a multicomponent clinical material like serum can influence kinetic parameters of the BChE. The observed inhibitory effect is dependent on serum dilution factor used in the assay.
Full Text Available Aurora Mocanu,1 Roxana Diana Pasca,1 Gheorghe Tomoaia,2 Corina Garbo,1 Petre T Frangopol,1 Ossi Horovitz,1 Maria Tomoaia-Cotisel11Chemical Engineering Department, Babes-Bolyai University, 2Orthopedic Department, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, RomaniaAbstract: Silver nanoparticles (AgNPs were prepared in aqueous colloid dispersions by the reduction of Ag+ with glucose in alkaline medium. Tetraethyl orthosilicate and l-asparagine were added as stabilizers of NPs. The AgNPs were characterized, and their interaction with three local anesthetics (procaine, dibucaine, or tetracaine was investigated. Optical spectra show the characteristic absorption band of AgNPs, due to surface plasmon resonance. Modifications in the position and shape of this band reflect the self-assembly of metal NPs mediated by anesthetic molecules and the progress in time of the aggregation process. Zeta-potential measuring was applied in order to characterize the electrostatic stability of the NPs. The size and shape of the AgNPs, as well as the features of the assemblies formed by their association in the presence of anesthetics, were evidenced by transmission electron microscopy images. Atomic force microscopy images showed the characteristics of the films of AgNPs deposited on glass support. The effect of the anesthetics could be described in terms of electrostatic forces between the negatively charged AgNPs and the anesthetic molecules, existing also in their cationic form at the working pH. But also hydrophobic and hydrogen bonding interactions between the coated nanoparticles and anesthetics molecular species should be considered.Keywords: self-assembled nanostructures, UV-vis spectra, TEM, AFM, zeta potential