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Indian Journal of Anaesthesia Jul 2017Dibucaine, a potent and toxic local anaesthetic, although currently withdrawn by the United States Food and Drug Administration for use as a spinal anaesthetic,...
Dibucaine, a potent and toxic local anaesthetic, although currently withdrawn by the United States Food and Drug Administration for use as a spinal anaesthetic, continues to remain available in many over-the-counter topical formulations.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.
PubMed: 28794532
DOI: 10.4103/ija.IJA_166_17 -
Talanta Jan 2015In this work, the competitive interaction between dibucaine and three fluorescent probes (i.e., berberine, palmatine, and coptisine) for occupancy of the cucurbit[7]uril...
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.
Topics: Anesthetics, Local; Berberine; Berberine Alkaloids; Binding, Competitive; Bridged-Ring Compounds; Dibucaine; Fluorescent Dyes; Humans; Hydrogen-Ion Concentration; Imidazoles; Kinetics; Limit of Detection; Solutions; Spectrometry, Fluorescence; Thermodynamics
PubMed: 25476359
DOI: 10.1016/j.talanta.2014.09.005 -
The Journal of Biological Chemistry 2021The mitochondrial calcium uniporter (MCU) and cyclophilin D (CyD) are key players in induction of the permeability transition pore (PTP), which leads to mitochondrial...
The mitochondrial calcium uniporter (MCU) and cyclophilin D (CyD) are key players in induction of the permeability transition pore (PTP), which leads to mitochondrial depolarization and swelling, the major signs of Ca-induced mitochondrial damage. Mitochondrial depolarization inhibits ATP production, whereas swelling results in the release of mitochondrial pro-apoptotic proteins. The extent to which simultaneous deletion of MCU and CyD inhibits PTP induction and prevents damage of brain mitochondria is not clear. Here, we investigated the effects of MCU and CyD deletion on the propensity for PTP induction using mitochondria isolated from the brains of MCU-KO, CyD-KO, and newly created MCU/CyD-double knockout (DKO) mice. Neither deletion of MCU nor of CyD affected respiration or membrane potential in mitochondria isolated from the brains of these mice. Mitochondria from MCU-KO and MCU/CyD-DKO mice displayed reduced Ca uptake and diminished extent of PTP induction. The Ca uptake by mitochondria from CyD-KO mice was increased compared with mitochondria from WT mice. Deletion of CyD prevented mitochondrial swelling and resulted in transient depolarization in response to Ca, but it did not prevent Ca-induced delayed mitochondrial depolarization. Mitochondria from MCU/CyD-DKO mice did not swell in response to Ca, but they did exhibit mild sustained depolarization. Dibucaine, an inhibitor of the Ca-activated mitochondrial phospholipase A2, attenuated and bovine serum albumin completely eliminated the sustained depolarization. This suggests the involvement of phospholipase A2 and free fatty acids. Thus, in addition to induction of the classical PTP, alternative deleterious mechanisms may contribute to mitochondrial damage following exposure to elevated Ca.
Topics: Animals; Brain; Calcium; Calcium Channels; Peptidyl-Prolyl Isomerase F; Gene Knockout Techniques; Mice; Mice, Knockout; Mitochondria; Mitochondrial Proteins
PubMed: 33864812
DOI: 10.1016/j.jbc.2021.100669 -
BMC Psychiatry Mar 2021Poisoning and deaths by organo-phosphorous (OP) compounds are one of the major causes of death in developing and poor countries, and a common admission in the emergency...
BACKGROUND
Poisoning and deaths by organo-phosphorous (OP) compounds are one of the major causes of death in developing and poor countries, and a common admission in the emergency ward and the ICU. OP compounds act by irreversibly binding to pseudocholinesterase enzyme and hence prolong the apnea in patients being given suxamethonium. We present a unusual case of OP poisoning (OPP) in which prolonged apnea ensued in a patient of severe depression following MECT (modified electroconvulsive therapy) in which suxamethonium was used as muscle relaxant, in whom we were cautious of the side-effect of prior organophosphorus poisoning. Since the cases of OPP are very high worldwide, a thorough knowledge of the interaction of the action of the drug and the receptors on which it acts takes pride of place. This article highlights the nuances in the field of psychiatry and anaesthesia in diagnosis and management of prolonged apnea after ECT.
CASE PRESENTATION
A 53/F patient consumed OP 38 days prior to MECT. Since existing literature recommend a delay of 4 weeks and a subminimal dose of suxamethonium to prevent prolonged apnea, both these points were taken into consideration. Despite 38 days post exposure to OP, and a dose of succinylcholine of < 0.3 mg/kg, the patient remained apneic for 3 h. Suxamethionum apnea was managed with elective ventilation. After recovery, patient had no residual effect. Subsequently her pseudocholinesterase levels were done which were found to be very low.
CONCLUSION
This case is being presented to emphasize that behaviour of post synaptic receptors cannot be relied upon after OP poisoning and pseudocholinesterase levels needs to be mandatorily checked, irrespective of duration post-exposure. In strong suspects dibucaine number and fluoride number also needs to be estimated.
Topics: Apnea; Electroconvulsive Therapy; Female; Humans; Neuromuscular Depolarizing Agents; Organophosphate Poisoning; Poisoning; Succinylcholine
PubMed: 33691646
DOI: 10.1186/s12888-021-03150-0 -
Molecules (Basel, Switzerland) Aug 2022In this work, magnetic tetraethylenepentamine (TEPA)-modified carboxyl-carbon nanotubes were synthesized, characterized, and used as adsorbents to conduct magnetic...
In this work, magnetic tetraethylenepentamine (TEPA)-modified carboxyl-carbon nanotubes were synthesized, characterized, and used as adsorbents to conduct magnetic solid-phase extraction (MSPE) for the preconcentration of seven local anesthetic drugs (procaine, lidocaine, mepivacaine, oxybuprocaine, bupivacaine, tetracaine, and cinchocaine) from human plasma. The separation and determination of analytes were performed on high-performance liquid chromatography with UV detection. Several factors affected the extraction efficiency, such as the amount of adsorbents used, extraction time, sample pH, and optimization of elution conditions. Under optimal conditions, satisfactory linear relationships were obtained in the range of 0.02-5.00 mg/L, with the limits of detection (LOD) ranging from 0.003 mg/L to 0.008 mg/L. The recoveries of analytes for spiked human plasma were in the range of 82.0-108%. Moreover, the precision with intra-day and inter-day RSD values were obtained in the range of 1.5-7.7% and 1.5-8.3%. The results indicated that this method could determine the concentration of seven local anesthetic drugs in human plasma with high precision and repeatability and provide support for the clinical monitoring of the concentration of local anesthetic drugs in human plasma.
Topics: Anesthetics, Local; Chromatography, High Pressure Liquid; Humans; Magnetic Phenomena; Nanotubes, Carbon; Solid Phase Extraction
PubMed: 36080279
DOI: 10.3390/molecules27175509 -
Spectrochimica Acta. Part A, Molecular... Jul 2021For the treatment of internal and external hemorrhoids, policresulen (POL) and cinchocaine hydrochloride (CIN) are used in combination. Using a new, simple, fast, and...
For the treatment of internal and external hemorrhoids, policresulen (POL) and cinchocaine hydrochloride (CIN) are used in combination. Using a new, simple, fast, and economical first-derivative synchronous fluorescence spectroscopic process, both drugs were simultaneously determined and validated. At Δλ60 nm and with a scanning rate of 600 nm/min, methanol was used as the solvent for both products. In the concentration ranges of 5.0-21.0 μg mL and 0.5-6.0 μg mL for POL and CIN, the amplitude-concentration plots were rectilinear. The detection limits were found to be 0.770 μg mL and 0.118 μg mL and the quantitation limits for POL and CIN were 2.541 μg mL and 0.391 μg mL. To evaluate all compounds in synthetic mixtures and medicinal dosage types, the proposed method has been successfully applied. These findings were in line with the results obtained using high-performance thin layer chromatography, the comparison process.
Topics: Cresols; Dibucaine; Drug Combinations; Formaldehyde; Ointments; Spectrometry, Fluorescence; Suppositories
PubMed: 33744839
DOI: 10.1016/j.saa.2021.119648 -
Dermatitis : Contact, Atopic,...Topical medications may lead to allergic contact dermatitis. This study characterized positive patch test reactions associated with medications in patients evaluated by...
BACKGROUND/OBJECTIVES
Topical medications may lead to allergic contact dermatitis. This study characterized positive patch test reactions associated with medications in patients evaluated by the North American Contact Dermatitis Group (NACDG).
METHODS
This study is a retrospective analysis of the NACDG data (2001-2018). Patients with at least 1 positive patch test reaction associated with a medication source were included. Allergens, reaction characteristics, clinical relevance, and source details were tabulated.
RESULTS
Of 43,722 patients, 6374 (14.6%) had positive allergic patch test reactions associated with 1 or more topical medication sources. Patients with versus without allergic reactions to medications were more likely to be older than 40 years (P < 0.0001) and/or have primary sites of dermatitis on the legs, anal/genital region, or trunk (P < 0.0001). There were 8787 reactions to NACDG allergens; the most common were neomycin (29.4%), bacitracin (29.1%), propylene glycol 100% (10.6%), tixocortol-17-pivalate (10.0%), lidocaine (7.9%), budesonide (4.9%), and dibucaine (4.4%). Propylene glycol 100% was the most common inactive ingredient (10.6%). Current relevance was present in 61.0%. A total of 6.5% of the individuals with medication allergy would have had 1 or more positive patch test reactions missed if only tested to the NACDG screening series.
CONCLUSIONS
Positive patch test reactions associated with topical medications were common (14.6%), and most were clinically relevant. Patients with topical medication allergy were twice as likely to have anal/genital involvement. Active ingredients, especially neomycin, bacitracin, and tixocortol-17-pivalate, were frequent culprits.
Topics: Allergens; Dermatitis, Allergic Contact; Humans; North America; Patch Tests; Retrospective Studies
PubMed: 34405832
DOI: 10.1097/DER.0000000000000777 -
Evidence-based Complementary and... 2022Alzheimer's disease (AD) is the most common type of dementia, and the abnormal hyperphosphorylation of the tau protein is the main component of its pathogenesis. Calpain...
Alzheimer's disease (AD) is the most common type of dementia, and the abnormal hyperphosphorylation of the tau protein is the main component of its pathogenesis. Calpain was found to be abnormally activated in neurofibrillary tangles (NFTs) in a previous report. Cornel iridoid glycosides (CIG) have been reported to reduce the hyperphosphorylation of tau protein. Nevertheless, the role of calpain in the reduction tau hyperphosphorylation by CIG remains unclear. In the present study, we investigated the effect of CIG on calpain activity through in vitro and in vivo experiments. Western blotting results suggested that CIG decreased the phosphorylation of tau at Ser 404 and Ser 262 sites in P301S mice. Moreover, CIG inhibited the activity of calpain and glycogen synthase kinase 3 (GSK-3) and enhanced the activity of protein phosphatase 2A (PP2A) both in vivo and in vitro. CIG also inhibited the activation of PP2A and reduced the GSK-3 activity caused by the calpain activator dibucaine. In addition, the main components of CIG, morroniside and loganin, play an equivalent role in reducing calpain activity, as the effect of their combined use is equivalent to that of CIG. The abovementioned findings revealed that CIG improved PP2A activity and reduced GSK-3 activity by adjusting the activity of calpain 1, leading to a reduction in the phosphorylation of tau. This study highlights the remarkable therapeutic potential of CIG for managing AD.
PubMed: 35096120
DOI: 10.1155/2022/9213046 -
Chemico-biological Interactions Oct 2020Two types of cholinesterases (ChEs) are present in mammalian blood and tissues: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). While AChE regulates...
Two types of cholinesterases (ChEs) are present in mammalian blood and tissues: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). While AChE regulates neurotransmission by hydrolyzing acetylcholine at the postsynaptic membranes and neuromuscular junctions, BChE in plasma has been suggested to be involved in detoxifying toxic compounds. This study was undertaken to establish the identity of circulating ChE activity in plasmas from domestic animals (bovine, ovine, caprine, porcine and equine) by assessing sensitivity to AChE-specific inhibitors (BW284c51 and edrophonium) and BChE-specific inhibitors (dibucaine, ethopropazine and Iso-OMPA) as well as binding to anti-FBS AChE monoclonal antibodies (MAbs). Based on the inhibition of ChE activity by ChE-specific inhibitors, it was determined that bovine, ovine and caprine plasma predominantly contain AChE, while porcine and equine plasma contain BChE. Three of the anti-FBS AChE MAbs, 4E5, 5E8 and 6H9, inhibited 85-98% of enzyme activity in bovine, ovine and caprine plasma, confirming that the esterase in these plasmas was AChE. These MAbs did not bind to purified recombinant human or mouse AChE, demonstrating that these MAbs were specific for AChEs from ruminant species. These MAbs did not inhibit the activity of purified human BChE, or ChE activity in porcine and equine plasma, confirming that the ChE in these plasmas was BChE. Taken together, these results demonstrate that anti-FBS AChE MAbs can serve as useful tools for distinguishing between AChEs from ruminant and non-ruminant species and BChEs.
Topics: Acetylcholinesterase; Animals; Animals, Domestic; Antibodies, Monoclonal; Butyrylcholinesterase; Cattle; Cholinesterase Inhibitors; Fetal Blood; Humans; Mice; Ruminants
PubMed: 32795450
DOI: 10.1016/j.cbi.2020.109225 -
Langmuir : the ACS Journal of Surfaces... Nov 2018Dibucaine (DBC) is one of the most potent long-acting local anesthetics, but it also has significant toxic side effects and low water solubility. Solid lipid...
Electron Paramagnetic Resonance and Small-Angle X-ray Scattering Characterization of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Dibucaine Encapsulation.
Dibucaine (DBC) is one of the most potent long-acting local anesthetics, but it also has significant toxic side effects and low water solubility. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been proposed as drug-delivery systems to increase the bioavailability of local anesthetics. The purpose of the present study was to characterize SLNs and NLCs composed of cetyl palmitate or myristyl myristate, a mixture of capric and caprylic acids (for NLCs only) plus Pluronic F68 prepared for the encapsulation of DBC. We intended to provide a careful structural characterization of the nanoparticles to identify the relevant architectural parameters that lead to the desirable biological response. Initially, SLNs and NLCs were assessed in terms of their size distribution, morphology, surface charge, and drug loading. Spectroscopic techniques (infrared spectroscopy and electron paramagnetic resonance, EPR) plus small-angle X-ray scattering (SAXS) provided information on the interactions between nanoparticle components and their structural organization. The sizes of nanoparticles were in the 180 nm range with low polydispersity and negative zeta values (-25 to -46 mV). The partition coefficient of DBC between nanoparticles and water at pH 8.2 was very high (>10). EPR (with doxyl-stearate spin labels) data revealed the existence of lamellar arrangements inside the lipid nanoparticles, which was also confirmed by SAXS experiments. Moreover, the addition of DBC increased the molecular packing of both SLN and NLC lipids, indicative of DBC insertion between the lipids, in the milieu assessed by spin labels. Such structural information brings insights into understanding the molecular organization of these versatile drug-delivery systems which have already demonstrated their potential for therapeutic applications in pain control.
Topics: Anesthetics, Local; Dibucaine; Drug Carriers; Electron Spin Resonance Spectroscopy; Myristates; Nanoparticles; Palmitates; Particle Size; Poloxamer; Scattering, Small Angle; X-Ray Diffraction
PubMed: 30299102
DOI: 10.1021/acs.langmuir.8b02559