RESUMEN

Background: The popularity of tortoises kept in captivity is increasing and has caused concern regarding the necessity to establish safe and straightforward anaesthesia for those reptiles. Aim: This study aimed to compare four protocols using levobupivacaine in spinal anaesthesia for the blockade of the caudal neuraxis of red-footed tortoises (Chelonoidis carbonarius). Methods: Twenty-four tortoises were randomly assigned into four groups: G1, levobupivacaine 0.75% (1.15 mg kg-1); G2, levobupivacaine 0.37% (1.15 mg kg-1); G3, levobupivacaine 0.75% (2.3 mg kg-1); and G4, levobupivacaine 0.75% (0.1 ml 5 cm-1 of straight carapace length). Tortoises were evaluated for respiratory rate, muscle relaxation, response to hindlimb or tail pinch, and cloacal reflex. Results: A 1.15 mg kg-1 dose of levobupivacaine 0.37% appears adequate for shorter procedures, whereas a 1.15 mg kg-1 dose of levobupivacaine 0.75% should be appropriate for longer procedures in red-footed tortoises. Conclusion: Our results are the first to show the effects of levobupivacaine on spinal anaesthesia in reptiles. Weight-based doses presented more intense and more homogeneous effects than carapace length-based doses in red-footed tortoises. Spinal anaesthesia of red-footed tortoises was safe and effective with any of the weight-based protocols.

Asunto(s)

Anestesia Raquidea , Anestésicos Locales , Levobupivacaína , Tortugas , Animales , Levobupivacaína/administración & dosificación , Levobupivacaína/farmacología , Anestesia Raquidea/veterinaria , Anestesia Raquidea/métodos , Anestésicos Locales/farmacología , Anestésicos Locales/administración & dosificación , Masculino , Femenino

RESUMEN

Nanostructured lipid carriers (NLC) have emerged as innovative drug delivery systems, offering distinct advantages over other lipid-based carriers, such as liposomes and solid lipid nanoparticles. Benzocaine (BZC), the oldest topical local anesthetic in use, undergoes metabolism by pseudocholinesterase, leading to the formation of p-aminobenzoic acid, a causative agent for allergic reactions associated with prolonged BZC usage. In order to mitigate adverse effects and enhance bioavailability, BZC was encapsulated within NLC. Utilizing a 23 factorial design, formulations comprising cetyl palmitate (solid lipid), propylene glycol monocaprylate (liquid lipid), and Pluronic F68 as surfactants were systematically prepared, with variations in the solid/liquid lipid mass ratios (60:40-80:20%), total lipid contents (15-25%), and BZC concentrations (1-3%). The optimized formulation underwent characterization by dynamic light scattering, differential scanning calorimetry, Raman imaging, X-ray diffraction, small-angle neutron scattering, nanotracking analysis, and transmission electron microscopy (TEM)/cryo-TEM, providing insights into the nanoparticle structure and the incorporation of BZC into its lipid matrix. NLCBZC exhibited a noteworthy encapsulation efficiency (%EE = 96%) and a 1 year stability when stored at 25 °C. In vitro kinetic studies and in vivo antinociceptive tests conducted in mice revealed that NLCBZC effectively sustained drug release for over 20 h and prolonged the anesthetic effect of BZC for up to 18 h. We therefore propose the use of NLCBZC to diminish the effective anesthetic concentration of benzocaine (from 20 to 3% or less), thus minimizing allergic reactions that follow the topical administration of this anesthetic and, potentially, paving the way for new routes of BZC administration in pain management.

Asunto(s)

Anestésicos Locales , Benzocaína , Portadores de Fármacos , Lípidos , Benzocaína/administración & dosificación , Benzocaína/química , Anestésicos Locales/administración & dosificación , Anestésicos Locales/química , Anestésicos Locales/farmacocinética , Anestésicos Locales/farmacología , Portadores de Fármacos/química , Animales , Lípidos/química , Ratones , Nanoestructuras/química , Liberación de Fármacos , Masculino , Nanopartículas/química

RESUMEN

The chemical structure of piperidine has a unique ability to combine with other molecular fragments. This fact makes it possible to actively use it as an effective basis for the creation of new drug-like substances. Thus, the aim of the current investigation was to study the acute toxicity, local anesthetic potency, and antiarrhythmic activity of the two new synthesized piperidine derivatives under laboratory codes LAS-286 and LAS-294 (local anesthetic substances). The Bulbring & Wajda animal model and method of determining the nociception threshold during electrical stimulation was used to investigate the action of the substance during infiltration anesthesia. An antiarrhythmic activity was observed by the aconitine-induced rat arrhythmia model. Additionally, these compounds were studied in relation to molecular docking to delineate the structure-activity relationships. The tested piperidine derivatives had a low toxicity in the subcutaneous and intravenous administration routes. The experimental results showed a higher prolonged and pronounced local anesthetic activity for LAS-286 at a 0.5% concentration, compared to the reference preparations. The low dosage of 0.1 mg/kg of LAS-294 demonstrated a pronounced preventive antiarrhythmic effect in 90% of cases on the development of mixed arrhythmia, caused by aconitine. The results of molecular docking confirmed a higher binding affinity of the tested piperidines with the Nav1.4 and Nav1.5 macromolecules. The results of the present study are very promising, because these piperidines have shown a high biological activity, which can suggest a potential therapeutic application in the future.

Asunto(s)

Anestésicos Locales , Antiarrítmicos , Simulación del Acoplamiento Molecular , Piperidinas , Animales , Antiarrítmicos/farmacología , Anestésicos Locales/farmacología , Piperidinas/farmacología , Piperidinas/química , Ratas , Masculino , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/tratamiento farmacológico , Relación Estructura-Actividad , Ratas Wistar , Modelos Animales de Enfermedad

RESUMEN

INTRODUCTION: Cardiac arrest or arrhythmia caused by bupivacaine may be refractory to treatment. Apelin has been reported to directly increase the frequency of spontaneous activation and the propagation of action potentials, ultimately promoting cardiac contractility. This study aimed to investigate the effects of apelin-13 in reversing cardiac suppression induced by bupivacaine in rats. METHODS: A rat model of cardiac suppression was established by a 3-min continuous intravenous infusion of bupivacaine at the rate of 5 mg.kg-1.min-1, and serial doses of apelin-13 (50, 150 and 450 µg.kg-1) were administered to rescue cardiac suppression to identify its dose-response relationship. We used F13A, an inhibitor of Angiotensin Receptor-Like 1 (APJ), and Protein Kinase C (PKC) inhibitor chelerythrine to reverse the effects of apelin-13. Moreover, the protein expressions of PKC, Nav1.5, and APJ in ventricular tissues were measured using Western blotting and immunofluorescence assay. RESULTS: Compared to the control rats, the rats subjected to continuous intravenous administration of bupivacaine had impaired hemodynamic stability. Administration of apelin-13, in a dose-dependent manner, significantly improved hemodynamic parameters in rats with bupivacaine-induced cardiac suppression (p < 0.05), and apelin-13 treatment also significantly upregulated the protein expressions of p-PKC and Nav1.5 (p < 0.05), these effects were abrogated by F13A or chelerythrine (p < 0.05). CONCLUSION: Exogenous apelin-13, at least in part, activates the PKC signaling pathway through the apelin/APJ system to improve cardiac function in a rat model of bupivacaine-induced cardiac suppression.

Asunto(s)

Bupivacaína , Cardiotoxicidad , Péptidos y Proteínas de Señalización Intercelular , Ratas Sprague-Dawley , Animales , Bupivacaína/toxicidad , Ratas , Masculino , Péptidos y Proteínas de Señalización Intercelular/farmacología , Péptidos y Proteínas de Señalización Intercelular/administración & dosificación , Cardiotoxicidad/etiología , Cardiotoxicidad/prevención & control , Proteína Quinasa C/metabolismo , Relación Dosis-Respuesta a Droga , Anestésicos Locales/farmacología , Modelos Animales de Enfermedad , Canal de Sodio Activado por Voltaje NAV1.5/metabolismo , Canal de Sodio Activado por Voltaje NAV1.5/efectos de los fármacos , Receptores Acoplados a Proteínas G/efectos de los fármacos , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Apelina , Benzofenantridinas

RESUMEN

Purpose: This study aimed to determine the onset and duration of action of 3 commercially available topical anesthetic solutions in Brazil, using the Cochet-Bonnet esthesiometer (Luneau®, Paris, France) and to quantitatively assess patient-reported discomfort during application. Methods: A prospective, randomized, masked, and double-blind study was conducted, involving 40 eyes from 21 patients. Patients were administered each one of the topical anesthetics weekly, and corneal sensitivity was measured using the Cochet-Bonnet esthesiometer's corneal touch threshold (CTT). Patients rated the burning sensation using a visual analogue scale (VAS). Results: Among the 21 patients (42.9% male), with a mean age of 31.95 years (±standard deviation = 10.17, range = 22.0-58.0), corneal sensitivity significantly decreased 30 s after application, returning to baseline after 30 min for all groups (P < 0.0001). Significant differences in CTT were observed at 5 min, with proparacaine exhibiting a superior anesthetic effect (P = 0.0003), at 10 min, where tetracaine displayed the most substantial anesthetic effect (P = 0.0135), and at 20 min, where tetracaine demonstrated the highest anesthetic efficacy (P < 0.0001). VAS scores indicated the most intense burning sensation with tetracaine (P < 0.0001). Men reported experiencing more discomfort during instillation compared with women (P = 0.0168). Conclusions: Proparacaine exhibited the fastest onset of action among the 3 topical anesthetics and provided a more comfortable eye sensation during instillation. However, tetracaine demonstrated the longest duration of action despite causing more discomfort.

Asunto(s)

Anestésicos Locales , Córnea , Procaína , Propoxicaína , Tetracaína , Humanos , Masculino , Femenino , Tetracaína/administración & dosificación , Tetracaína/farmacología , Adulto , Método Doble Ciego , Propoxicaína/administración & dosificación , Propoxicaína/farmacología , Anestésicos Locales/administración & dosificación , Anestésicos Locales/farmacología , Persona de Mediana Edad , Estudios Prospectivos , Córnea/efectos de los fármacos , Procaína/administración & dosificación , Procaína/farmacología , Procaína/análogos & derivados , Procaína/efectos adversos , Adulto Joven , Soluciones Oftálmicas/administración & dosificación , Dimensión del Dolor/métodos

RESUMEN

The objective of this work was to carry out a systematic review on the effectiveness of local anesthetics as antimicrobial agents against Staphylococcus spp. Searches were performed in the PubMed, Web of science, Scopus, Embase and Lilacs databases. As inclusion criteria, complete original articles, with in vitro experimental tests with the application of selected anesthetics and bacteria of the genus Staphylococcus spp. This review followed the methodological checklist for writing papers reporting systematic reviews by the PRISMA statement. The risk of bias was assessed according to the JBI critical appraisal checklist. Analysis was performed using an anesthetic-moderated simple linear regression model. This systematic review was registered by the Open Science Framework-OSF ( https://doi.org/10.17605/OSF.IO/C5JM7 ). Initially, 1141 articles were found, of which, after careful selection, 52 articles were analyzed. Lidocaine was the most commonly used anesthetic, being evaluated in 35 of the articles. S. aureus ATCC 25923 was the standard microorganism in 17 articles. The impact of the anesthetic concentration in relation to the antimicrobial effect was evaluated and the results showed that there was no statistically significant difference. (F [5, 12] = 0.688 p = 0.642), even when taking into account the moderator effect of anesthetics individually. Therefore, although the antimicrobial effect of local anesthetics was demonstrated in 82.7% of the studies evaluated, great heterogeneity of the results was found, which made it impossible to carry out a meta-analysis and make recommendations based on the evidence.

Asunto(s)

Anestésicos Locales , Staphylococcus , Anestésicos Locales/farmacología , Staphylococcus/efectos de los fármacos , Humanos , Infecciones Estafilocócicas/microbiología , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana

RESUMEN

Electroejaculation (EE) represents the main technique for semen collection from domestic and wild animals independently of libido. However, the technique is associated with intense involuntary muscle contractions, vocalization, ataxia and lying down, caused by the electric stimulation of the nerves in the caudal epigastric region. These clinical manifestations represent important indicators of discomfort. In this context, the objective of this study was to evaluate two protocols of local anaesthetic blockade and two anatomical access for pharmacological desensitization of the caudal epigastric innervation as alternatives to promote comfort and reduce stress associated with EE in rams. For the study, four clinically healthy Dorper rams were selected. All animals were subjected to a design consisting of five semen collection treatments (n = 3 collections per treatment): T1-control, conventional EE without local anaesthetic blockade; T2, EE with ventral blockade (VB) of epigastric innervation using lidocaine hydrochloride 2%; T3, EE with VB of epigastric innervation using a combination of lidocaine hydrochloride 2% and fentanyl citrate; T4, EE with blockade of epigastric innervation through the perineal access using lidocaine hydrochloride 2%; T5, EE with blockade of epigastric innervation through the perineal access using a combination of lidocaine hydrochloride and fentanyl citrate. Seminal samples resulting from EE were subjectively evaluated for sperm motility and concentration, vigour and volume. Additionally, blood serum samples were collected for quantification of cortisol and creatine kinase (CK) enzyme. Assessments of stress and discomfort were conducted by measuring blood pressure, heart rate (HR) and respiratory rate (RR), as well as observing involuntary muscle contractions, ataxia and animal vocalization. No variations in blood pressure, sperm motility, vigour, CK, and cortisol were observed among the treatments. Individual variations were observed for the occurrence of vocalization (p = .0066), but there were no differences between the groups. Anaesthetic blockades conducted using the combination of lidocaine and fentanyl resulted in a lower incidence of ataxia during EE (p < .0001). It is concluded that the combination of fentanyl citrate and lidocaine hydrochloride results in less discomfort for animals undergoing EE, regardless of the anatomical access used for local anaesthetic blockades.

Asunto(s)

Anestésicos Locales , Enfermedades de las Ovejas , Masculino , Animales , Ovinos , Anestésicos Locales/farmacología , Hidrocortisona , Motilidad Espermática , Dolor/veterinaria , Lidocaína/farmacología , Fentanilo/farmacología , Ataxia/veterinaria

RESUMEN

This crossover study aimed to compare the anesthetic effects of buffered 2% articaine with 1:200,000 epinephrine with that of non-buffered 4% articaine with 1:200,000 epinephrine. Forty-seven volunteers were administered two doses of anesthesia in the buccal region of the second mandibular molars in two sessions using 1.8 mL of different local anesthetic solutions. The onset time and duration of pulp anesthesia, soft tissue pressure pain threshold, and the score of pain on puncture and burning during injection were evaluated. The operator, volunteers, and statistician were blinded. There were no significant differences in the parameters: onset of soft tissue anesthesia (p = 0.80), duration of soft tissue anesthesia (p = 0.10), onset of pulpal anesthesia in the second (p = 0.28) and first molars (p = 0.45), duration of pulp anesthesia of the second (p = 0.60) and first molars (p = 0.30), pain during puncture (p = 0.82) and injection (p = 0.80). No significant adverse events were observed. Buffered 2% articaine with 1:200,000 epinephrine did not differ from non-buffered 4% articaine with 1:200,000 epinephrine considering anesthetic success, safety, onset, duration of anesthesia, and pain on injection.

Asunto(s)

Carticaína , Lidocaína , Humanos , Carticaína/farmacología , Lidocaína/farmacología , Estudios Cruzados , Anestésicos Locales/farmacología , Epinefrina/farmacología , Anestesia Local , Dolor , Diente Molar , Método Doble Ciego

RESUMEN

OBJECTIVES: A randomized controlled clinical trial was developed to evaluate the cardiovascular effects of local anesthetics with vasoconstrictors (LAVC) in healthy and hypertensive patients undergoing teeth extraction with lidocaine 2% with epinephrine 1:100,000. MATERIALS AND METHODS: Twenty patients were divided into control (CG - normotensive patients) and experimental groups (EG - hypertensive patients). The variables analyzed were heart rate (HR), oxygen saturation (SO2), systolic and diastolic blood pressure (SBP and DBP), serum catecholamine concentration (dopamine, epinephrine, and norepinephrine), ventricular and supraventricular extrasystoles (VES and SVES respectively), and ST segment depression. Data was obtained in three different moments (initial, trans, and final). Blood samples were taken to measure the catecholamines, and a Holter device was used to measure data from the electrocardiogram including a 24-h postoperative evaluation period. The Mann-Whitney test was used to identify differences between the two groups, and the Friedman test with the adjusted Wilcoxon posttest was used for intragroup evaluation for repeated measures. RESULTS: The EG presented a lower O2S in the initial period (p = 0,001) while the sysBP showed a statistical difference for the three evaluation periods with the EG presenting the highest values. The VES was higher for the EG during the 24-h postoperative evaluation period (p = 0,041). The SVES and the serum catecholamines showed were similar between the groups. The intragroup analysis revealed significant statistical difference for the sysBP in the EG with the trans period presenting the highest measurements. The extrasystole evaluation showed that the 24-h postoperative period presented most events with only the CG not presenting statistical difference for the variable VES during this period (p = 0,112). No ST segment depression was noticed for both groups. CONCLUSIONS: Teeth extraction with LAVC can be safely executed in hypertensive patients. Blood pressure should be monitored in these patients since the sysBP presented significant differences during the surgical procedures. Cardiac arrhythmia and the serum catecholamines concentration levels seem not to be altered by the surgical procedure. Also, serum catecholamines do not influence cardiovascular changes in this type of surgery. CLINICAL RELEVANCE: LAVC can be safely used in hypertensive patients and does not increase the risk of arrhythmias or cardiac ischemia.

Asunto(s)

Anestésicos Locales , Hipertensión , Humanos , Anestésicos Locales/farmacología , Catecolaminas/farmacología , Epinefrina , Lidocaína , Vasoconstrictores , Presión Sanguínea , Frecuencia Cardíaca , Extracción Dental

RESUMEN

INTRODUCTION: Spinal anaesthesia consists of administering a local anaesthetic in the subarachnoid space, thus causing sensory, motor, and autonomic nerve conduction block. Currently, recovery from spinal anaesthesia is evaluated by the return of motor function, without considering the autonomic blockade, which is responsible for most complications of the technique. Heart rate variability (HRV) is an indirect method to measure the autonomic nervous system and may be useful in assessing autonomic recovery after spinal anaesthesia. The study objective was to evaluate the autonomic function, through HRV, at the moment of return of motor function in patients who received spinal anaesthesia when clonidine is used as an adjuvant. MATERIAL AND METHODS: This was a randomised, double-blind clinical trial. The sample consisted of 64 ASA I-II patients who underwent spinal anaesthesia and were divided into 2 groups. Group C received 20 mg of bupivacaine with 75 mcg of clonidine, and group B received 20 mg of bupivacaine. HRV was evaluated at rest (T1) and at the time of motor function recovery (T2). Data were collected using a Polar V800® heart rate monitor and then analysed and filtered using Kubios 3.0® software. RESULTS: There was no difference in the values of the low-frequency/high-frequency (LF/HF) ratio, Poincaré plot standard deviation (SD2/SD1), detrended fluctuation analysis (DFAα1, DFAα2), or correlation dimension (D2) indices in any of the groups between the 2 moments. In the clonidine group, there was a difference only in approximate entropy (ApEn), where a P of 0.0124 was obtained considering a 95% confidence interval ranging from 17.83 to 141.47. CONCLUSIONS: There was no significant difference between the duration of sympathetic blockade and motor blockade in spinal anaesthesia.

Asunto(s)

Anestesia Raquidea , Humanos , Clonidina/farmacología , Frecuencia Cardíaca , Anestésicos Locales/farmacología , Bupivacaína/farmacología

RESUMEN

OBJECTIVE: To determine the proximal diffusion distance of radiopaque contrast medium and mepivacaine/methylene blue solution and incidence of inadvertent intrasynovial and intravascular injections of modified sesamoid nerve block (MASB) when compared with traditional plantar nerve analgesia techniques of the equine distal hind limb. SAMPLE: Ex vivo model: 18 hind limbs; and in vivo model: 5 horses in a crossover study. METHODS: In the ex vivo model, a mepivacaine/methylene blue solution was used to compare the diffusion distance between MASB, basisesamoid block (BSB), and traditional low plantar block (TLPB). Ten minutes after injection, skin was dissected and proximal diffusion distance of the dye patch was measured. In the in vivo model, both hind limbs were injected with radiopaque contrast medium with either MASB or TLPB. Ten minutes after injection, a radiograph was acquired and the proximal diffusion of the contrast medium patch was measured. RESULTS: In the ex vivo model, solution proximal diffusion distance for MASB was significantly longer than BSB (P < .050) and significantly shorter than TLPB (P < .050). Both techniques reached the proximal aspect of DFTS similarly (P = .289), and no difference in the incidence of intrasynovial or intravascular injections was observed (P = .292). In the in vivo model, contrast medium proximal diffusion of MASB was significantly shorter than TLPB (P < .050). The proportion of injections that diffused subcutaneously to the proximal aspect of the proximal pouch of the DFTS was not significantly different between techniques (P = .136). No difference in the incidence of DFTS intrasynovial or intravascular injections was observed (P = .305). CLINICAL RELEVANCE: MASB presented significantly more proximal diffusion than BSB and less proximal diffusion than TLPB, consistently reached the proximal aspect of DFTS, and presented a very low risk of intrasynovial and intravascular injections.

Asunto(s)

Mepivacaína , Bloqueo Nervioso , Caballos , Animales , Mepivacaína/farmacología , Estudios Cruzados , Azul de Metileno , Medios de Contraste/farmacología , Bloqueo Nervioso/veterinaria , Anestésicos Locales/farmacología

Asunto(s)

Humanos , Niño , Adolescente , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Analgésicos/uso terapéutico , Anestésicos Locales/uso terapéutico , Antiinflamatorios/uso terapéutico , Antisépticos Bucales/uso terapéutico , Interacciones Farmacológicas , Quimioterapia Combinada , Contraindicaciones de los Medicamentos , Analgésicos/farmacología , Anestésicos Locales/farmacología , Fitoterapia , Antiinflamatorios/farmacología , Antisépticos Bucales/farmacología

RESUMEN

Tetracaine (TTC) is a local anesthetic broadly used for topical and spinal blockade, despite its systemic toxicity. Encapsulation in nanostructured lipid carriers (NLC) may prolong TTC delivery at the site of injection, reducing such toxicity. This work reports the development of NLC loading 4% TTC. Structural properties and encapsulation efficiency (%EE > 63%) guided the selection of three pre-formulations of different lipid composition, through a 23 factorial design of experiments (DOE). DLS and TEM analyses revealed average sizes (193-220 nm), polydispersity (< 0.2), zeta potential |- 21.8 to - 30.1 mV| and spherical shape of the nanoparticles, while FTIR-ATR, NTA, DSC, XRD and SANS provided details on their structure and physicochemical stability over time. Interestingly, one optimized pre-formulation (CP-TRANS/TTC) showed phase-separation after 4 months, as predicted by Raman imaging that detected lack of miscibility between its solid (cetyl palmitate) and liquid (Transcutol) lipids. SANS analyses identified lamellar arrangements inside such nanoparticles, the thickness of the lamellae been decreased by TTC. As a result of this combined approach (DOE and biophysical techniques) two optimized pre-formulations were rationally selected, both with great potential as drug delivery systems, extending the release of the anesthetic (> 48 h) and reducing TTC cytotoxicity against Balb/c 3T3 cells.

Asunto(s)

Anestésicos Locales/farmacología , Proliferación Celular , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Liberación de Fármacos , Nanoestructuras/administración & dosificación , Tetracaína/farmacología , Anestésicos Locales/química , Animales , Células 3T3 BALB , Ratones , Nanoestructuras/química , Tetracaína/química

RESUMEN

Anesthetic failure is common in dental inflammation processes, even when modern agents, such as articaine, are used. Nanostructured lipid carriers (NLC) are systems with the potential to improve anesthetic efficacy, in which active excipients can provide desirable properties, such as anti-inflammatory. Coupling factorial design (FD) for in vitro formulation development with in vivo zebrafish tests, six different NLC formulations, composed of synthetic (cetyl palmitate/triglycerides) or natural (avocado butter/olive oil/copaiba oil) lipids were evaluated for loading articaine. The formulations selected by FD were physicochemically characterized, tested for shelf stability and in vitro release kinetics and had their in vivo effect (anti-inflammatory and anesthetic effect) screened in zebrafish. The optimized NLC formulation composed of avocado butter, copaiba oil, Tween 80 and 2% articaine showed adequate physicochemical properties (size = 217.7 ± 0.8 nm, PDI = 0.174 ± 0.004, zeta potential = - 40.2 ± 1.1 mV, %EE = 70.6 ± 1.8) and exhibited anti-inflammatory activity. The anesthetic effect on touch reaction and heart rate of zebrafish was improved to 100 and 60%, respectively, in comparison to free articaine. The combined FD/zebrafish approach was very effective to reveal the best articaine-in-NLC formulation, aiming the control of pain at inflamed tissues.

Asunto(s)

Anestesia/métodos , Antiinflamatorios/farmacología , Bradicardia/tratamiento farmacológico , Carticaína/farmacología , Portadores de Fármacos/química , Inflamación/tratamiento farmacológico , Nanoestructuras/química , Anestésicos Locales/química , Anestésicos Locales/farmacología , Animales , Antiinflamatorios/química , Carticaína/química , Liberación de Fármacos , Excipientes/química , Nanoestructuras/administración & dosificación , Pez Cebra

RESUMEN

Among the physical conditions that impair memory performance, pain is one of the most prevalent. However, the mechanisms by which pain impairs memory are largely unknown. In this study, we asked whether pain affects memory acquisition, consolidation and retrieval as well as whether memory impairment depends on pain intensity. Wistar rats received a hind paw injection of formalin (1%) at different phases of object recognition test. The injection of formalin after training but not before training or testing impaired object recognition memory. We concluded that pain impairs the consolidation but not acquisition or retrieval of object recognition memory, which is a subtype of declarative memory. Morphine, at a dose that did not affect object recognition memory in control rats, drastically reduced formalin-induced nociceptive behavior without reversing memory impairment. A lower dose of formalin (0.25%) induced less nociceptive behavior, but similar memory impairment. There is no statistical correlation between the intensity of nociceptive response and the performance in object recognition test. However, when formalin-induced nociceptive response was blocked by a local anesthetic, memory impairment was prevented. These findings suggest that pain-induced impairment in the consolidation of object recognition memory does not directly depend on the intensity of nociceptive activity.

Asunto(s)

Consolidación de la Memoria/fisiología , Memoria/fisiología , Dolor/fisiopatología , Anestésicos Locales/farmacología , Animales , Masculino , Recuerdo Mental/fisiología , Dolor/metabolismo , Ratas , Ratas Wistar , Reconocimiento en Psicología/fisiología

RESUMEN

STUDY OBJECTIVE: In this study, we aimed to compare the antimicrobial effects of bupivacaine and fentanyl citrate and to reveal the impact on antimicrobial effect potential in the case of combined use. DESIGN: In vitro prospective study. SETTING: University Clinical Microbiology Laboratory. MEASUREMENTS: In our study, in vitro antimicrobial effect of 0.05 mg.mL-1 fentanyl citrate, 5 mg.mL-1 bupivacaine were tested against Staphylococcus aureus American Type Culture Collection (ATCC) 29213, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883, Escherichia coli ATCC 25922 and Candida albicans ATCC 10231 as Group F (Fentanyl Citrate) and Group B (Bupivacaine), respectively. S. aureus ATCC 29213, P. aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883 and Escherichia coli ATCC 25922 were cultured onto Mueller Hinton agar (Oxoid, UK) plates and Candida albicans ATCC 10231 were cultured onto Sabouraud dextrose agar (Oxoid, UK) plates for 18-24 hours at 37°C. MAIN RESULTS: In terms of inhibition zone diameters, S. Aureus ATCC 29213, P. aeruginosa ATCC 27853, and C. albicans ATCC10231 values obtained after 12 and 24 hours of incubation were significantly higher in Group F than Group B (p < 0.001). In terms of inhibition zone diameters, E. coli ATCC 25922, and K. pneumomiae ATCC 13883 values obtained after 12 and 24hours of incubation were significantly higher in Group B than Group F (p < 0.001, E. coli 12ª hour p = 0.005). CONCLUSIONS: Addition of fentanyl to Local Anesthetics (LAs) is often preferred in regional anesthesia applications in today's practice owing especially to its effect on decreasing the local anesthetic dose and increasing analgesia quality and patient satisfaction. However, when the fact that fentanyl antagonized the antimicrobial effects of LAs in the studies is taken into account, it might be though that it contributes to an increase in infection complications. When the fact that fentanyl citrate, which was used in our study and included hydrochloric acid and sodium hydroxide as protective agents, broadened the antimicrobial effect spectrum of LAs, had no antagonistic effect and showed a synergistic antimicrobial effect against E. Coli is considered, we are of the opinion that the addition of fentanyl to LAs would contribute significantly in preventing the increasing regional anesthesia infection complications.

Asunto(s)

Anestésicos Locales/farmacología , Antiinfecciosos/farmacología , Bupivacaína/farmacología , Fentanilo/farmacología , Anestésicos Locales/administración & dosificación , Antiinfecciosos/administración & dosificación , Bupivacaína/administración & dosificación , Sinergismo Farmacológico , Fentanilo/administración & dosificación , Ácido Clorhídrico/farmacología , Pruebas de Sensibilidad Microbiana , Estudios Prospectivos , Hidróxido de Sodio/farmacología

RESUMEN

Abstract Study objective: In this study, we aimed to compare the antimicrobial effects of bupivacaine and fentanyl citrate and to reveal the impact on antimicrobial effect potential in the case of combined use. Design: In vitro prospective study. Setting: University Clinical Microbiology Laboratory. Measurements: In our study, in vitro antimicrobial effect of 0.05 mg.mL-1 fentanyl citrate, 5 mg.mL-1 bupivacaine were tested against Staphylococcus aureus American Type Culture Collection (ATCC) 29213, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883, Escherichia coli ATCC 25922 and Candida albicans ATCC 10231 as Group F (Fentanyl Citrate) and Group B (Bupivacaine), respectively. S. aureus ATCC 29213, P. aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883 and Escherichia coli ATCC 25922 were cultured onto Mueller Hinton agar (Oxoid, UK) plates and Candida albicans ATCC 10231 were cultured onto Sabouraud dextrose agar (Oxoid, UK) plates for 18-24 hours at 37 °C. Main results: In terms of inhibition zone diameters, S. Aureus ATCC 29213, P. aeruginosa ATCC 27853, and C. albicans ATCC10231 values obtained after 12 and 24 hours of incubation ​​were significantly higher in Group F than Group B (p < 0.001). In terms of inhibition zone diameters, E. coli ATCC 25922, and K. pneumomiae ATCC 13883 values obtained after 12 and 24 hours of incubation ​​were significantly higher in Group B than Group F (p < 0.001, E. coli 12ª hour p = 0.005). Conclusions: Addition of fentanyl to Local Anesthetics (LAs) is often preferred in regional anesthesia applications in today's practice owing especially to its effect on decreasing the local anesthetic dose and increasing analgesia quality and patient satisfaction. However, when the fact that fentanyl antagonized the antimicrobial effects of LAs in the studies is taken into account, it might be though that it contributes to an increase in infection complications. When the fact that fentanyl citrate which was used in our study and included hydrochloric acid and sodium hydroxide as protective agents, broadened the antimicrobial effect spectrum of LAs, had no antagonistic effect and showed a synergistic antimicrobial effect against E. Coli is considered, we are of the opinion that the addition of fentanyl to LAs would contribute significantly in preventing the increasing regional anesthesia infection complications.

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Resumo Objetivo: O objetivo do presente estudo foi comparar os efeitos antimicrobianos da bupivacaína e citrato de fentanil e revelar o impacto no potencial do efeito antimicrobiano no caso de uso combinado. Desenho: Estudo prospectivo in vitro. Local: Laboratório de Microbiologia Clínica da Universidade. Medidas: Em nosso estudo, os efeitos antimicrobianos in vitro do citrato de fentanil na concentração de 0,05 mg.mL-1 - Grupo F e da bupivacaína na concentração de 5 mg.mL-1 - Grupo B foram testados em culturas de Staphylococcus aureus ATCC 29213 (do inglês American Type Culture Collection 29213), Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883, Escherichia coli ATCC 25922 e Candida albicans ATCC 10231. As culturas de S. aureus ATCC 29213, P. aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883 e Escherichia coli ATCC 25922 foram semeadas em placas de ágar Mueller Hinton (Oxoid, Reino Unido), e a cultura de Candida albicans ATCC 10231 foi realizada em placa de ágar Sabouraud dextrose (Oxoid, Reino Unido) durante 18-24 horas a 37 °C. Principais resultados: Com relação ao diâmetro da zona de inibição, os valores de S. aureus ATCC 29213, P. aeruginosa ATCC 27853 e C. albicans ATCC10231 obtidos após 12 e 24 horas de incubação foram significantemente maiores no Grupo F do que no Grupo B (p < 0,001). Os valores do diâmetro da zona de inibição das culturas de E. coli ATCC 25922 e K. pneumomiae ATCC 13883 obtidos após 12 e 24 horas de incubação foram significantemente maiores no Grupo B do que no Grupo F (p < 0,001, E. coli na 12ª hora p = 0,005) Conclusões: A preferência atual e frequente pela adição de fentanil aos Anestésicos Locais (AL) para a realização de anestesia regional se deve sobretudo à possibilidade de redução da dose do anestésico local, a melhora na qualidade da analgesia e a satisfação do paciente. No entanto, ao considerar estudos em que o fentanil antagonizou o efeito antimicrobiano dos AL, pode-se pensar que esse fato contribua para aumento de complicação infecciosa. O citrato de fentanil usado em nosso estudo, contendo ácido clorídrico e hidróxido de sódio como agentes conservantes, ampliou o espectro de efeitos antimicrobianos dos AL, não teve efeito antagônico e demonstrou efeito antimicrobiano sinérgico contra a E. coli. Acreditamos que a adição de fentanil aos anestésicos locais traria importante contribuição na prevenção das crescentes complicações por infecção da anestesia regional.

Asunto(s)

Bupivacaína/farmacología , Fentanilo/farmacología , Anestésicos Locales/farmacología , Antiinfecciosos/farmacología , Hidróxido de Sodio/farmacología , Bupivacaína/administración & dosificación , Pruebas de Sensibilidad Microbiana , Fentanilo/administración & dosificación , Estudios Prospectivos , Sinergismo Farmacológico , Ácido Clorhídrico/farmacología , Anestésicos Locales/administración & dosificación , Antiinfecciosos/administración & dosificación

RESUMEN

Topical anesthetics are widely applied in order to relieve the discomfort and anxiety caused by needle insertion and other painful superficial interventions at the oral cavity. So far, there are no commercially available effective topical anesthetic formulations for that purpose, and the most of developments are related to hydrophilic and low mucoadhesive forms. Therefore, we have prepared different hybrid nanofilms composed of biopolymer matrices (chitosan, pectin, and chitosan-pectin) blended with nanostructured lipid carriers (NLC) loading the eutectic mixture of 5% lidocaine-prilocaine (LDC-PLC), in order to fulfill this gap in the market. These dual systems were processed as hybrid nanofilms by the solvent/casting method, and its mucoadhesive, structural and mechanical properties were detailed. The most appropriate hybrid nanofilm combined the advantages of both pectin (PCT) and NLC components. The resultant material presented sustained LDC-PLC release profile for more than 8 h; permeation across porcine buccal mucosa almost twice higher than control and non-cytotoxicity against 3T3 and HACAT cell lines. Then, the in vivo efficacy of PCT/NLC formulation was compared to biopolymer film and commercial drug, exhibiting the longest-lasting anesthetic effect (> 7 h), assessed by tail flick test in mice. These pectin-based hybrid nanofilms open perspectives for clinical trials and applications beyond Dentistry.

Asunto(s)

Anestesia Local/métodos , Anestésicos Locales/uso terapéutico , Odontología/métodos , Portadores de Fármacos/uso terapéutico , Nanoestructuras/uso terapéutico , Dolor/prevención & control , Células 3T3 , Anestésicos Locales/farmacología , Animales , Biopolímeros/uso terapéutico , Células HaCaT , Humanos , Combinación Lidocaína y Prilocaína/farmacología , Combinación Lidocaína y Prilocaína/uso terapéutico , Ratones , Mucosa Bucal/efectos de los fármacos , Porcinos

RESUMEN

INTRODUCTION: The association between Local Anesthetics (LAs) and Neuromuscular Blocking (NMB) drugs in clinical practice, and the possibility of interaction between these drugs has been investigated. LAs act on neuromuscular transmission in a dose-dependent manner and may potentiate the effects of NMB drugs. OBJECTIVE: The aim of this study was to evaluate, in an experimental model, the effect of lidocaine and racemic bupivacaine on neuromuscular transmission and the influence on neuromuscular blockade produced by atracurium. METHODS: Male Wistar rats, weighing from 250 g to 300g were used. The preparation was set up based on a technique proposed by Bülbring. Groups were formed (n = 5) according to the drug studied: lidocaine 20 µg.mL-1 (Group I); racemic bupivacaine 5 µg.mL-1 (Group II); atracurium 20 µg.mL-1 (Group III); atracurium 20 µg.mL-1 in a preparation previously exposed to lidocaine 20 µg.mL-1 and racemic bupivacaine 5 µg.mL-1, Groups IV and V, respectively. The following parameters were assessed: 1) Amplitude of hemi diaphragmatic response to indirect stimulation before and 60 minutes after addition of the drugs; 2) Membrane Potentials (MP) and Miniature Endplate Potentials (MEPPs). RESULTS: Lidocaine and racemic bupivacaine alone did not alter the amplitude of muscle response. With previous use of lidocaine and racemic bupivacaine, the neuromuscular blockade (%) induced by atracurium was 86.66 ± 12.48 and 100, respectively, with a significant difference (p = 0.003), in comparison to the blockade produced by atracurium alone (55.7 ± 11.22). These drugs did not alter membrane potential. Lidocaine initially increased the frequency of MEPPs, followed by blockade. With the use of bupivacaine, the blockade was progressive. CONCLUSIONS: Lidocaine and racemic bupivacaine had a presynaptic effect expressed by alterations in MEPPs, which may explain the interaction and potentiation of NMB produced by atracurium.

Asunto(s)

Anestésicos Locales/farmacología , Atracurio/farmacología , Bupivacaína/farmacología , Lidocaína/farmacología , Bloqueo Neuromuscular , Unión Neuromuscular/efectos de los fármacos , Unión Neuromuscular/fisiología , Animales , Interacciones Farmacológicas , Masculino , Ratas , Ratas Wistar

RESUMEN

Abstract Introduction: The association between local anesthetics (LA) and neuromuscular blocking (NMB) drugs in clinical practice, and the possibility of interaction between these drugs has been investigated. LAs act on neuromuscular transmission in a dose-dependent manner and may potentiate the effects of NMB drugs. Objective: The aim of this study was to evaluate, in an experimental model, the effect of lidocaine and racemic bupivacaine on neuromuscular transmission and the influence on neuromuscular blockade produced by atracurium. Methods: Male Wistar rats, weighing from 250 to 300 g were used. The preparation was set up based on a technique proposed by Bülbring. Groups were formed (n = 5) according to the drug studied: lidocaine 20 µg.mL−1 (Group I); racemic bupivacaine 5 µg.mL−1 (Group II); atracurium 20 µg.mL−1 (Group III); atracurium 20 µg.mL−1 in a preparation previously exposed to lidocaine 20 µg.mL−1 and racemic bupivacaine 5 µg.mL−1, Groups IV and V, respectively. The following parameters were assessed: 1) Amplitude of hemi diaphragmatic response to indirect stimulation before and 60 minutes after addition of the drugs; 2) Membrane potentials (MP) and miniature endplate potentials (MEPPs). Results: Lidocaine and racemic bupivacaine alone did not alter the amplitude of muscle response. With previous use of lidocaine and racemic bupivacaine, the neuromuscular blockade (%) induced by atracurium was 86.66 ± 12.48 and 100, respectively, with a significant difference (p = 0.003), in comparison to the blockade produced by atracurium alone (55.7 ± 11.22). These drugs did not alter membrane potential. Lidocaine initially increased the frequency of MEPPs, followed by blockade. With the use of bupivacaine, the blockade was progressive. Conclusions: Lidocaine and racemic bupivacaine had a presynaptic effect expressed by alterations in MEPPs, which may explain the interaction and potentiation of NMB produced by atracurium.

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Resumo Introdução: A associação de anestésicos locais (AL) com bloqueadores neuromusculares (BNM) na prática clínica e a possibilidade de interação entre esses fármacos têm sido investigadas. Objetivo: Avaliar, em modelo experimental, o efeito da lidocaína e da bupivacaína racêmica na transmissão neuromuscular e sua influência no bloqueio neuromuscular produzido pelo atracúrio. Método: Ratos machos da linhagem Wistar, peso entre 250 e 300 g. A preparação foi feita de acordo com a técnica proposta por Bulbring. Grupos (n = 5) de acordo com o fármaco em estudo: lidocaína 20 µg.mL-1 (Grupo I); bupivacaína racêmica 5 µg.mL-1 (Grupo II); atracúrio 20 µg.mL-1 (Grupo III); atracúrio 20 µg.mL-1 em preparação previamente exposta a lidocaína 20 µg.mL-1 e bupivacaína racêmica 5 µg.mL-1, Grupos IV e V, respectivamente. Foram avaliados: 1) A amplitude das respostas do hemidiafragma à estimulação indireta antes e 60 minutos após a adição dos fármacos; 2) Os potenciais de membrana (PM) e os potenciais de placa terminal em miniatura (PPTM). Resultados: Os AL, isoladamente, não alteraram a amplitude das respostas musculares. Com o uso prévio dos AL, o bloqueio neuromuscular (%) do atracúrio foi 86,66 ± 12,48 e 100, respectivamente, com diferença significante (p= 0,003) em relação ao produzido pelo atracúrio isoladamente (55,7 ± 11,22). Não alteraram o PM. A lidocaína inicialmente aumentou a frequência dos PPTM, seguido de bloqueio; com a bupivacaína, o bloqueio foi progressivo. Conclusão: A lidocaína e a bupivacaína racêmica apresentaram efeito pré-sináptico expresso por alterações nos PPTM, podem justificar a potencialização do bloqueio neuromuscular produzido pelo atracúrio.

Asunto(s)

Animales , Masculino , Ratas , Atracurio/farmacología , Bupivacaína/farmacología , Bloqueo Neuromuscular , Anestésicos Locales/farmacología , Lidocaína/farmacología , Unión Neuromuscular/efectos de los fármacos , Unión Neuromuscular/fisiología , Ratas Wistar , Interacciones Farmacológicas