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The review article discusses in detail the problem of complications in maternity patients associated with spinal anesthesia and cesarean section surgery. The evidence base demonstrating the risk of complications in pregnant women with the development of acute neurological conditions is presented. The problems of the toxic effect of a local anesthetic (bupivacaine) and the consequences of a coronavirus infection on the body of pregnant women are considered separately.

We have previously developed ammonium sulphate gradient loaded liposomes to encapsulate dibucaine. Thus, the purpose of this study was to evaluate the pre-clinical safety and effectiveness of this novel ionic liposomal formulation of dibucaine (DBC), as described in previous work. Effectiveness was evaluated in vivo on Wistar rats (n = 8) that received plain DBC or liposomal DBC (DBCLUV). Control empty liposomes (without DBC) or saline were also used as control. Sciatic nerve block was performed using the formulations or controls (0.4 mL). A hindpaw incision-based postoperative pain model was used to evaluate mechanical hypersensitivity with von Frey filaments. To verify antiinflamatory activity protein levels of TNF-α, IL-1β, substance P and CGRP were measured by ELISA in the hindpaw tissue after 1 and 6 hours of the incision. To corroborate drug safety, sciatic nerve Schwann cell cultures were treated with the aforementioned formulations and assessed for cell viability (MTT assay) and death (flow cytometry assay). Histopathology of the tissues surrounding the sciatic nerve region was also assessed 2 and 7 days after treatment. All animals presented post incisional hypersensitivity and DBCLUV showed longer analgesic effect (p < 0.001). DBCLUV reduced TNF-α and CGRP levels (p < 0.05). Histopathological evaluation showed greater inflammatory reaction after the administration of control liposomes when compared to DBC (p < 0.05). There was no difference in Schwann cell viability and death between plain and encapsulated DBC. DBCLUV was safe and enhanced anaesthesia duration due to slow release of dibucaine from ammonium sulphate gradient loaded liposomes. [ABSTRACT FROM AUTHOR]

Mitochondrial membranes are pointed out as the site of cardiotoxic action of local anaesthetics. Its three main phospholipids components are phosphatidylcholine, phosphatidylethanolamine and cardiolipin. Cardiolipins, in eukaryotes, are only found in mitochondria and are essential for the maintenance of its integrity and dynamics. Fluorescence and nuclear magnetic resonance spectroscopy were used to study the interactions of a local anaesthetics, Dibucaine (DBC), with different mitochondrial membrane models constituted by combinations of its three main lipid components in which cardiolipin was a natural extract (CL mix). Both CL mix presence/absence and its percentage in the model membranes were evaluated. Fluorescence spectroscopy showed that DBC lowered the transition temperature of all membrane models understudy. DBC partition showed to be dependent of CL mix presence and phosphatidylethanolamine:CL ratio. Furthermore, the maximum emission wavelength (λ max) exhibited a notorious decreased with increasing phospholipid to DBC ratio, in all the membrane models containing CL mix. Nevertheless, it remained approximately the same in the membrane without CL mix. This indicates a differential membrane localization of the anaesthetics, dependent on the membrane models used. NMR results showed that DBC interaction and location in the membrane models is mainly influenced by CL mix presence, and DBC can significant alter lipid systems properties e.g. percentage and type of lipid phase present. Taken all together it was shown that DBC interaction and location are largely dependent on the membrane model system. Furthermore, DBC is able to produce significant changes in the lipidic systems which might help to explain its high toxicity. Unlabelled Image • Dibucaine location and partition is largely dependent on the membrane model system. • Dibucaine alters the mean lipid transition temperatures of the mitochondrial models. • Cardiolipin and phosphatidylethanolamine:CL ratio govern Dibucaine partition. • Dibucaine presence alters the percentage and type of membrane lipid phase present. • Dibucaine influence on the membrane properties might explain its high toxicity. [ABSTRACT FROM AUTHOR]

Electrochemical characterization and detection of protonated dibucaine (DIC+) at microinterface array across water|1,6-dichlorohexane were performed using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Some thermodynamic parameters of dibucaine, such as the standard transfer potential, the Gibbs energy of transfer and the partition coefficient, were estimated by CV. In addition to the analytical parameters, the impact of bovine serum albumin (BSA) on dibucaine detection (in artificial serum matrices) was also investigated. DPV was applied to detect a lower concentration of DIC+, resulting in a detection limit of 0.9 ± 0.06 µM. While the presence of BSA affected CV, demonstrated as reduced current responses, DPV was confirmed to be an efficient method for lowering concentrations of the dibucaine detection in the artificial serum matrix in the presence of BSA, with a limit of detection (LOD) of 1.9 ± 0.12 µM.

Dibucaine, a potent and toxic local anaesthetic, although currently withdrawn by the United States Food and Drug Administration for use as a spinal anaesthetic, continues to remain available in many over-the-counter topical formulations. Systemic toxicity following oral ingestion of local anaesthetics is rare. We report a case of accidental ingestion of dibucaine (ear drops) in a 7-year-old child who developed diplopia, giddiness, ventricular premature contractions and a right bundle branch block. We also present a brief discussion on the pharmacologic and toxicity profile of dibucaine, the Naranjo algorithm for assessing causality in case of adverse drug reactions and a review of current guidelines on the management of local anaesthetic systemic toxicity.

Administration of local anesthetics is one of the most effective pain control techniques for postoperative analgesia. However, anesthetic agents easily diffuse into the injection site, limiting the time of anesthesia. One approach to prolong analgesia is to entrap local anesthetic agents in nanostructured carriers (e.g., liposomes). Here, we report that using an ammonium sulphate gradient was the best strategy to improve the encapsulation (62.6%) of dibucaine (DBC) into liposomes. Light scattering and nanotracking analyses were used to characterize vesicle properties, such as, size, polydispersity, zeta potentials, and number. In vitro kinetic experiments revealed the sustained release of DBC (50% in 7 h) from the liposomes. In addition, in vitro (3T3 cells in culture) and in vivo (zebrafish) toxicity assays revealed that ionic-gradient liposomes were able to reduce DBC cyto/cardiotoxicity and morphological changes in zebrafish larvae. Moreover, the anesthesia time attained after infiltrative administration in mice was longer with encapsulated DBC (27 h) than that with free DBC (11 h), at 320 μM (0.012%), confirming it as a promising long-acting liposome formulation for parenteral drug administration of DBC. [ABSTRACT FROM AUTHOR]

Male infertility is a worldwide problem but few treatments, especially irradiation-induced testicular injury. The aim of this research was to investigate novel drugs for the treatment of irradiation-induced testicular injury. We administered dibucaine (0.8 mg/kg) intraperitoneally to male mice (6 mice per group) after five consecutive daily 0.5 Gy whole-body irradiation, and evaluated its ameliorating efficacy by testicular HE staining and morphological measurements. Drug affinity responsive target stability assay (Darts) were used to find target protein and pathway; mouse primary Leydig cells were isolated and to explore the mechanism (Flow cytometry, Western blot, and Seahorse palmitate oxidative stress assays); finally rescue experiments were completed by combining dibucaine with fatty acid oxidative pathway inhibitors and activators. The testicular HE staining and morphological measurements in dibucaine treatment group was significantly better than that in irradiation group (P < 0.05); sperm motility and mRNA levels of spermatogenic cell markers were also higher than those in the latter (P < 0.05). Darts and Western blot results showed that dibucaine targets CPT1A and downregulate fatty acid oxidation. Flow cytometry, Western blot, and Palmitate oxidative stress assays of primary Leydig cells demonstrated that dibucaine inhibits fatty acid oxidation in Leydig cells. Dibucaine combined with etomoxir/baicalin confirmed that its inhibition of fatty acid oxidation was beneficial in ameliorating irradiation-induced testicular injury. In conclusion, our data suggest that dibucaine ameliorates irradiation-induced testicular injury in mice by inhibiting fatty acid oxidation in Leydig cells. This will provide novel ideas for the treatment of irradiation-induced testicular injury. [Display omitted] • For the first time, dibucaine has been shown to ameliorate irradiation-induced testicular injury. • The inhibition of fatty acid oxidation processes, is essential for ameliorating irradiation-induced testicular injury. • Primary Leydig cells (not TM3) highly depend on fatty acid oxidation and are key to ameliorate irradiated testicular injury. • Darts and molecular docking proved, dibucaine specifically binds and inhibit CPT1A (a key protein in fatty acid oxidation). [ABSTRACT FROM AUTHOR]

The sustainable and green chemistry principles enable scientists to protect and benefit the economy, people and the planet by finding creative and innovative ways to reduce waste, conserve energy, and discover replacements for hazardous substances. In this work, an environmentally friendly ion selective electrode (ISE) potentiometric method was developed for the determination of cinchocaine hydrochloride (CIN) in presence of its degradation products either in bulk powder or in its combined pharmaceutical formulation with betametahsone valerate. Two novel CIN-selective electrodes were fabricated and evaluated. The fabrication of electrodes was based on sodium tetrakis [3,5-bis (trifluoromethyl)phenyl]borate as a cationic exchanger in a PVC matrix with 2-nitrophenyl octyl ether (2-NPOE) as a plasticizer and using 2-hydroxy propyl-β-cyclodextrin (2-HP β-CD) as an ionophore. A comparative study was conducted using two designed CIN-selective electrodes; a conventional liquid inner contact, sensor 1, and a glassy carbon solid contact electrode, sensor 2. Sensor 1 has a linear dynamic range of 3.0 × 10-5 mol L-1 to 1.0 × 10-2 mol L-1, with a Nernstian slope of 54.89 mV/decade and a detection limit of 5.01 × 10-6 mol/L. Sensor 2 shows linearity over the concentration range of 1.0 × 10-5 mol L-1 to 1.0 × 10-2 mol L-1, with a Nernstian slope of 57.01 mV/decade and a limit of detection of 2.51 × 10-6 mol L-1 which is much improved as a result of diminishing ion fluxes in this solid contact ion-selective electrode. The present electrodes show clear selectivity for CIN from several inorganic, structurally related organic molecules, sugars, co-formulated drug, some common drug excipients and its degradation products. The results obtained by the proposed sensors were statistically analyzed and compared with those obtained by official method. No significant difference for either accuracy or precision was observed. [ABSTRACT FROM AUTHOR]

Cinchocaine hydrochloride (CIN) and betamethasone valerate (BMV) are co-formulated in pharmaceutical formulations that could be used for local treatment of hemorrhoids. Both drugs are susceptible to hydrolytic degradation. Two sensitive and precise stability-indicating chromatographic methods were developed for the simultaneous determination of both active pharmaceutical ingredients. The developed methods were applied for quantitation of CIN and BMV in their pure forms, in presence of their corresponding degradation products and in their pharmaceutical formulation. The first method was a high performance liquid chromatographic (HPLC) one, separation and quantitation was achieved using a Waters Spheriosorb® 5 μm ODS2 C18 analytical column and an isocratic mobile phase formed of acetonitrile-acetate buffer (pH 6.5 ± 0.1) in a ratio of (55:45, v/v). The mobile phase was pumped at a flow rate of 1.2 mL/min. UV-detection was done at 240 nm using photodiode array detector. The second method was based on thin layer chromatography (TLC) fractionation coupled with densitometric determination. Separation was done on high performance thin layer chromatography (HPTLC) silica gel 60F254 plates using a developing system formed of chloroform-toluene-ethanol-acetic acid in a ratio of (4.5:4.5:1:1, by volume). The separated bands were scanned densitometrically at 240 nm. For the HPLC method, linearity was confirmed over concentration ranges of 4-300 and 4-350 μg/mL for CIN and BMV, respectively. For the HPTLC-densitometric method, the obtained ranges were 0.5-12 and 0.5-10 μg/band for CIN and BMV, respectively. The developed methods were optimized and validated according to the ICH guidelines. CIN acid degradation products were separated and identified by mass spectroscopy. The developed HPLC method was used to study the kinetics of acid and alkali degradation of the both drugs. The results obtained were statistically analyzed and compared with those obtained by applying the official methods for both drugs. [ABSTRACT FROM AUTHOR]

Ketoprofen is one of the non-steroidal anti-inflammatory drugs used for fomentation. It is associated with undesirable photosensitivity caused by UV irradiation. Moreover, it induces photodegradation, including decarboxylation, when exposed to UV irradiation. In this study, we attempted to identify compounds that can inhibit the photodegradation of ketoprofen. UV irradiation of ketoprofen follows first-order reaction kinetics and yields three photoproducts. Aqueous solutions containing ketoprofen generate free radicals when it was irradiated with UV. We considered that these free radicals react with ketoprofen. Antioxidants inhibit the photodegradation of ketoprofen. On the other hand, a local anesthetic, dibucaine hydrochloride, was also effective in inhibiting the photodegradation of ketoprofen. We evaluated the difference in the mechanism of inhibition between the antioxidants and the local anesthetic. In conclusion, both antioxidants and dibucaine hydrochloride are effective inhibitors of the photodegradation of ketoprofen. [ABSTRACT FROM AUTHOR]

Dibucaine (DBC) is among the more potent long-acting local anesthetics (LA), and it is also one of the most toxic. Over the last decades, solid lipid nanoparticles (SLN) have been developed as promising carriers for drug delivery. In this study, SLN formulations were prepared with the aim of prolonging DBC release and reducing its toxicity. To this end, SLN composed of two different lipid matrices and prepared by two different hot-emulsion techniques (high-pressure procedure and sonication) were compared. The colloidal stability of the SLN formulations was tracked in terms of particle size (nm), polydispersity index (PDI), and zeta potential (mV) for 240 days at 4 °C; the DBC encapsulation efficiency was determined by the ultrafiltration/centrifugation method. The formulations were characterized by differential scanning calorimetry (DSC), electron paramagnetic resonance (EPR), and release kinetic experiments. Finally, the in vitro cytotoxicity against 3T3 fibroblast and HaCaT cells was determined, and the in vivo analgesic action was assessed using the tail flick test in rats. Both of the homogenization procedures were found suitable to produce particles in the 200 nm range, with good shelf stability (240 days) and high DBC encapsulation efficiency (~72⁻89%). DSC results disclosed structural information on the nanoparticles, such as the lower crystallinity of the lipid core vs. the bulk lipid. EPR measurements provided evidence of DBC partitioning in both SLNs. In vitro (cytotoxicity) and in vivo (tail flick) experiments revealed that the encapsulation of DBC into nanoparticles reduces its intrinsic cytotoxicity and prolongs the anesthetic effect, respectively. These results show that the SLNs produced are safe and have great potential to extend the applications of dibucaine by enhancing its bioavailability.

In this study, we investigated the effects of drugs on membrane function in which lipid peroxidation was inhibited by the antioxidant Trolox (TRO) in liposomes containing egg yolk lecithin. Local anesthetics (LAs), such as lidocaine (LID) and dibucaine (DIB), were used as model drugs. The effect of LAs on the inhibitory activity of TRO was evaluated by calculating the p I 50 from the inhibition constant K calculated by curve fitting. p I 50 TRO indicates the strength of TRO membrane protective function. p I 50 LA indicates the strength of LA activity. LAs inhibited lipid peroxidation in a dose-dependent manner and decreased p I 50 TRO . The effect of DIB on p I 50 TRO was 1.9 times more than that of LID. This result indicated that LA may improve the fluidity of the membrane, which may facilitate the migration of TRO from the membrane to the liquid phase. As a result, TRO is less likely to suppress lipid peroxidation within the lipid membrane, possibly resulting in a decrease in p I 50 TRO . The effect of TRO on p I 50 LA was found to be similar in both, indicating that it did not depend on the type of the model drug. These results suggest that our developed procedure successfully quantified the effects of LAs on lipid membrane functions. We were able to obtain the characteristics of model drugs independent of TRO by simultaneously measuring and analyzing the lipid peroxidation inhibitory activities of TRO and model drugs in liposomes.

The intracellular membrane domain (IMD) is a laterally discrete region of the mycobacterial plasma membrane, enriched in the subpolar region of the rod-shaped cell. Here, we report genome-wide transposon sequencing to discover the controllers of membrane compartmentalization in Mycobacterium smegmatis. The putative gene cfa showed the most significant effect on recovery from membrane compartment disruption by dibucaine. Enzymatic analysis of Cfa and lipidomic analysis of a cfa deletion mutant (Δ cfa ) demonstrated that Cfa is an essential methyltransferase for the synthesis of major membrane phospholipids containing a C 19:0 monomethyl-branched stearic acid, also known as tuberculostearic acid (TBSA). TBSA has been intensively studied due to its abundant and genus-specific production in mycobacteria, but its biosynthetic enzymes had remained elusive. Cfa catalyzed the S -adenosyl-l-methionine-dependent methyltransferase reaction using oleic acid-containing lipid as a substrate, and Δ cfa accumulated C 18:1 oleic acid, suggesting that Cfa commits oleic acid to TBSA biosynthesis, likely contributing directly to lateral membrane partitioning. Consistent with this model, Δ cfa displayed delayed restoration of subpolar IMD and delayed outgrowth after bacteriostatic dibucaine treatment. These results reveal the physiological significance of TBSA in controlling lateral membrane partitioning in mycobacteria. IMPORTANCE As its common name implies, tuberculostearic acid is an abundant and genus-specific branched-chain fatty acid in mycobacterial membranes. This fatty acid, 10-methyl octadecanoic acid, has been an intense focus of research, particularly as a diagnostic marker for tuberculosis. It was discovered in 1934, and yet the enzymes that mediate the biosynthesis of this fatty acid and the functions of this unusual fatty acid in cells have remained elusive. Through a genome-wide transposon sequencing screen, enzyme assay, and global lipidomic analysis, we show that Cfa is the long-sought enzyme that is specifically involved in the first step of generating tuberculostearic acid. By characterizing a cfa deletion mutant, we further demonstrate that tuberculostearic acid actively regulates lateral membrane heterogeneity in mycobacteria. These findings indicate the role of branched fatty acids in controlling the functions of the plasma membrane, a critical barrier for the pathogen to survive in its human host.

Butyrylcholinesterase (BChE) activity assay and inhibitor phenotyping can help to identify individuals at risk of prolonged paralysis following the administration of neuromuscular blocking agents, like succinylcholine, pesticides and nerve agents. In this study, the activity of BChE and its sensitivity to inhibition by dibucaine and fluoride was evaluated in 1200 Polish healthy individuals. In addition, molecular analysis of all exons, exon-intron boundaries and the 3′UTR sequence of the BCHE gene was performed in a group of 72 subjects with abnormal BChE activity (<2000 U/L and >5745 U/L) or with DN (Dibucaine Number) or FN (Fluoride-Number) values outside the reference range (DN < 78 and FN < lower than wild type). In a studied group, BChE activity range was similar to those observed in other populations. BChE activity screening allowed to detect UA and UF phenotypes in 26 (2.2%) and 15 (1.2%) individuals, respectively. Observed UA or UF phenotypes were confirmed by direct sequencing and heterozygous c.293A > G or c.1253G > T substitutions were identified in all cases. Nine out of 18 (50%) individuals with BChE activity below 2000 U/L had a mutation in 5′UTR (32G/A), intron 2 (c.1518-121T/C) or exon 4 (c.1699G/A; the K variant mutation). Majority of the individuals with BChE activity ≥6000 U/L were wild type. To summarize, the range of BChE activity in a Polish population is similar to those observed in other countries. We conclude that the BChE phenotyping assay is a reliable method for identification of individuals with the UA and UF genotypes. [ABSTRACT FROM AUTHOR]

Background: Identification of novel drug-target interactions (DTIs) is important for drug discovery. Experimental determination of such DTIs is costly and time consuming, hence it necessitates the development of efficient computational methods for the accurate prediction of potential DTIs. To-date, many computational methods have been proposed for this purpose, but they suffer the drawback of a high rate of false positive predictions. Results: Here, we developed a novel computational DTI prediction method, DASPfind. DASPfind uses simple paths of particular lengths inferred from a graph that describes DTIs, similarities between drugs, and similarities between the protein targets of drugs. We show that on average, over the four gold standard DTI datasets, DASPfind significantly outperforms other existing methods when the single top-ranked predictions are considered, resulting in 46.17% of these predictions being correct, and it achieves 49.22% correct single top ranked predictions when the set of all DTIs for a single drug is tested. Furthermore, we demonstrate that our method is best suited for predicting DTIs in cases of drugs with no known targets or with few known targets. We also show the practical use of DASPfind by generating novel predictions for the Ion Channel dataset and validating them manually. Conclusions: DASPfind is a computational method for finding reliable new interactions between drugs and proteins. We show over six different DTI datasets that DASPfind outperforms other state-of-the-art methods when the single top-ranked predictions are considered, or when a drug with no known targets or with few known targets is considered. We illustrate the usefulness and practicality of DASPfind by predicting novel DTIs for the Ion Channel dataset. The validated predictions suggest that DASPfind can be used as an efficient method to identify correct DTIs, thus reducing the cost of necessary experimental verifications in the process of drug discovery. [ABSTRACT FROM AUTHOR]

In many anesthesia textbooks written in English, lidocaine, tetracaine, bupivacaine, ropivacaine, and chloroprocaine are listed as useful local anesthetics for spinal anesthesia. In contrast, T-cain is not included in these lists, even though it has been reported to be suitable for spinal anesthesia in Japan. T-cain was developed as a local anesthetic in the early 1940s by Teikoku Kagaku Sangyo Inc. in Itami, Japan, by replacing a methyl group on tetracaine (Pantocaine) with an ethyl group. T-cain was clinically approved for topical use in Japan in November 1949, and a mixture of dibucaine and T-cain (Neo-Percamin S) was approved for spinal use in May 1950. Simply because of a lack of foreign marketing strategy, T-cain has never attracted global attention as a local anesthetic. However, in Japan, T-cain has been used topically or intrathecally (as Neo-Percamin S) for more than 60 years. Other than the side effects generally known for all local anesthetics, serious side effects have not been reported for T-cain. In fact, several articles have reported that T-cain decreases the neurotoxicity of dibucaine. In this historical review, the characteristics of T-cain and its rise to become a major spinal anesthetic in Japan are discussed. [ABSTRACT FROM AUTHOR]

Zolpidem (ZPD) is widely described for the short-term treatment of insomnia. We have developed and validated a simple and rapid liquid chromatography analytical method using tandem mass spectrometry (LC–MS/MS) for the quantification of ZPD in human plasma. Using dibucaine as an internal standard (IS), the analyte was extracted with methyl t -butyl ether (MTBE). Chromatographic separation of ZPD was performed on a reversed-phase Luna C 18 column (50 mm × 2.0 mm i.d., 5 μm particles) with a mobile phase of 10 mM ammonium formate buffer (pH 3.0)–methanol (15:85, v/v) at a flow rate of 250 μm/min. The total run-time was 2.5 min and the retention times of ZPD and IS were 0.66 and 0.74 min, respectively. The mass-to-charge transition monitored for quantification of ZPD and IS was 308.2 → 235.2 and 344.0 → 271.0, respectively. The lower limit of quantification (LLOQ) using 100 μL of human plasma was 0.05 ng/mL and the calibration curves were linear over a range of 0.05–200 ng/mL ( r 2 > 0.9964). The mean accuracy and precision for intra- and inter-run validation of ZPD were within acceptable limits. In the present LC–MS/MS method, we showed improved sensitivity for quantification of the ZPD in human plasma using lower volume of plasma compared with previously described analytical methods for ZPD. This validated method was successfully applied to a pharmacokinetic study in humans. [ABSTRACT FROM AUTHOR]

In this research, Ag(I) nanoparticle with 4-nitro phenylcyanamide ligand, [AgL], where L = 4-nitro phenylcyanamide (4-NOpcyd), was synthesized successfully. FT-IR, H-NMR, TGA, and UV-Vis studies were done for the structural and thermal characterization of the Ag(I) nanoparticle. The spherical morphology of silver nanoparticles was confirmed from SEM image. The transmission electron microscopy image showed that the particle size dimensions of silver nanoparticles were about 1.5-5 nm. Furthermore, Ag(I) nanoparticle was immobilized on the surface of a glassy carbon electrode (GCE), and the electroactivity behavior was investigated by cyclic voltammetry and differential pulse voltammetry (DPV). The obtained [AgL]-modified GCE showed high catalytic activity for the oxidation of dibucaine and naphazoline. The peak current of differential pulse voltammograms of dibucaine and naphazoline increased linearly with their concentration in the ranges of 2.17-5.74 µM naphazoline and 18.5-72.2 µM dibucaine. The detection limits for dibucaine and naphazoline were 0.002 and 0.009 µM, respectively. In addition, the obtained [AgL]-modified GCE was investigated for the simultaneous determination of dopamine (DA) and acetaminophen (AP). In DPV technique, both DA and AP give sensitive oxidation peaks at 130 and 312 mV, respectively. Under the optimized experimental conditions, DA and AP give linear response over the range of 5-200 µmol L ( r = 0.996) and 5-300 µmol L ( r = 0.994), respectively. The lower detection limits were found to be 0.7 for DA and 0.5 µmol L for AP. The investigated method showed good stability, reproducibility [1.4 % (DA) and 2.5 % (AP)], and repeatability (1.8 %). [ABSTRACT FROM AUTHOR]

In this work, the competitive interaction between dibucaine and three fluorescent probes (i.e., berberine, palmatine, and coptisine) for occupancy of the cucurbit[7]uril (CB[7]) cavity was studied by fluorescence spectra, UV–visible absorption spectra, 1 H NMR spectra, and theoretical calculations in acidic aqueous solution. Based on the fluorescence enhancement of berberine, palmatine, and coptisine upon binding with CB[7], respectively, a series of fluorescence detection methods for dibucaine were proposed. At the optimized conditions, the fluorescence intensity of berberine-CB[7], palmatine-CB[7], and coptisine-CB[7] complexes showed negative correlation to the concentration of dibucaine, which led to a series of simple and sensitive fluorescence methods for the determination of dibucaine for the first time. Linear ranges obtained in the detection of the dibucaine were 0.018–3.34 μmol L −1 , 0.032–4.47 μmol L −1 , and 0.079–4.42 μmol L −1 with detection limits of 6.0 nmol L −1 , 12.0 nmol L −1 , and 25.0 nmol L −1 , respectively. Moreover, the proposed method was successfully applied for the determination of the drug in biological fluids. The competitive mode based on CB[7] superstructure provided a promising assay strategy for fluorescence detection in various potential applications. [ABSTRACT FROM AUTHOR]

Dibucaine, a potent and toxic local anaesthetic, although currently withdrawn by the United States Food and Drug Administration for use as a spinal anaesthetic, continues to remain available in many over-the-counter topical formulations. Systemic toxicity following oral ingestion of local anaesthetics is rare. We report a case of accidental ingestion of dibucaine (ear drops) in a 7-year-old child who developed diplopia, giddiness, ventricular premature contractions and a right bundle branch block. We also present a brief discussion on the pharmacologic and toxicity profile of dibucaine, the Naranjo algorithm for assessing causality in case of adverse drug reactions and a review of current guidelines on the management of local anaesthetic systemic toxicity. [ABSTRACT FROM AUTHOR]

BACKGROUND Allergic contact dermatitis (ACD) to lidocaine is rising in prevalence. This is due to a growing number of over-the-counter (OTC) products containing topical amide and ester anesthetics. The phenomenon poses a real threat to the authors' surgical anesthetic options. OBJECTIVE To investigate the epidemiology of topical anesthetic ACD in British Columbia, Canada and provide an approach for clinicians to deal with this problem. MATERIALS AND METHODS A retrospective chart review of 1,819 patients who underwent patch testing at the University of British Columbia Contact Dermatitis Clinic between January 2009 and June 2013 was completed. The authors also performed a detailed review of Canadian OTC preparations containing lidocaine in 2013. RESULTS The prevalence of ACD to local anesthetics is significant at 2.4%. The most common allergen is benzocaine (45%) followed by lidocaine (32%) and dibucaine (23%). CONCLUSION The proportion of ACD caused by lidocaine is higher than expected. This is likely secondary to an increase in OTC medicaments containing lidocaine. Patients who are patch test-positive to a local anesthetic should be challenged intradermally to confirm clinical relevance. Because ACD is a delayed Type IV hypersensitivity reaction (localized dermatitis), the risk of anaphylaxis is not a concern. [ABSTRACT FROM AUTHOR]

The effect of intralesional treatment (IL) with Procaine and Dibucaine was compared with standard dosages of Glucantime® administered intramuscularly (IM) to attain clinical and parasitological cures in skin lesions in outbred male hamsters infected with Leishmania (Viannia) braziliensis. Results revealed that all drugs tested reduced significantly (P < 0.01) average lesion sizes in experimental animals when compared with those untreated. Local treatment with dibucaine was as clinically efficient as systemic Glucantime®, and more successful for clinical resolution than with procaine. Viable amastigotes were detected in nodules and/or scars in 100% of the evaluated hamsters 75-165 days after the end of the treatment ended, using smears, conventional histopathology, culture in NNN medium and the indirect immunoperoxidase method, suggesting that measurement of lesion sizes is not a valid criterion for evaluating the chemotherapeutic efficiency in experimental CL. The therapeutic clinic effectiveness of local anesthetics appeared to be associated with their half-life times as well as their lipid solubility. Preliminarily, these results appeared to support the inclusion of “cainic” local anesthetics as part of the alternative armamentarium in the treatment of animal and human cutaneous leishmaniasis (CL).