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Formulation and topical delivery of lidocaine and prilocaine with the use of Pheroid™ technology / Dirkie Cornelia Nell.Nell, Dirkie Cornelia January 2012 (has links)
Local anaesthetics are used regularly in the medical world for a variety of different procedures. Topical anaesthetics are used largely in minor skin breaking procedures, laceration repair and minor surgical procedures such as laryngoscopy, oesophagoscopy or urethroscopy (Franchi et al., 2008:186e1). The topical means of application of a local anaesthetic is non-invasive and painless that results in a good patient acceptability profile (Little et al., 2008:102). An existing commercial topical anaesthetic product contains a eutectic mixture of the amide-type local anaesthetics lidocaine hydrochloride (HCl) and prilocaine hydrochloride (HCl). This commercial product takes up to an hour to produce an anaesthetic effect. This is considered as a disadvantage in the use of topical anaesthetics, an hour waiting time is not always ideal in certain medical circumstances (Wahlgren & Quiding, 2000:584).
This study compared the lag times, transdermal and topical delivery of lidocaine HCl and prilocaine HCl from four different semi-solid formulations with the inclusion of a current commercial product. One of the formulated semi-solid formulations included Pheroid™ technology, a novel skin-friendly delivery system developed by the Unit for Drug Research and Development at the North-West University, Potchefstroom Campus, South Africa.
The skin is the body’s first line of defence against noxious external stimuli. It is considered the largest organ in the body with an intensive and complex structure. It consists of five layers with the first outer layer, the stratum corneum, the most impermeable (Williams, 2003:1). The stratum corneum has excellent barrier function characteristics and is the cause for the time delay in the transdermal delivery of active pharmaceutical ingredients (API) (Barry, 2007:569). Local anaesthetics need to penetrate all the epidermal skin layers in order to reach their target site, the dermis. Skin appendages as well as blood vessels and skin nerve endings are located in the dermis. Local anaesthetics have to reach the free nerve endings in the dermis in order to cause a reversible block on these nerves for a local anaesthetic effect (Richards & McConachie, 1995:41).
Penetration enhancement strategies for the transdermal delivery of lidocaine and prilocaine have been investigated and include methods like liposomal entrapment (Franz-Montan et al., 2010; Müller et al., 2004), micellisation (Scherlund et al., 2000), occlusive dressing (Astra Zeneca, 2006), heating techniques (Masud et al., 2010) and iontophoresis (Brounéus et al., 2000). The Pheroid™ delivery system has improved the transdermal delivery of several compounds with its enhanced entrapment capabilities. Pheroid™ consists mainly of unsaturated essential fatty-acids, non-harmful substances that are easily recognised by the body (Grobler et al., 2008:285). The morphology and size of Pheroid™ is easily manipulated because it is a submicron emulsion type formulation which provides it with a vast flexibility profile (Grobler et al., 2008:284). Vesicular entrapment was used to entrap lidocaine HCl and prilocaine HCl in the Pheroid™ and incorporated into an emulgel formulation. An emulgel without the inclusion of Pheroid™ was formulated for comparison with the Pheroid™ emulgel as well as with a hydrogel. Pheroid™ solution was prepared and compared to a phosphate buffer solution (PBS) without Pheroid™, both containing lidocaine HCl and prilocaine HCl as APIs.
Franz cell type transdermal diffusion studies were performed on the four semi-solid formulations (emulgel, Pheroid™ emulgel, hydrogel and the commercial product) and two solutions (PBS and Pheroid™). The diffusion studies were performed over a 12 h period followed by the tape stripping of the skin after each diffusion study. Caucasian female abdominal skin was obtained with consent from the donors. The skin for the diffusion cells were prepared by using a Zimmer Dermatome®. PBS (pH 7.4) was prepared as the receptor phase of the diffusion studies. The receptor phase was extracted at certain pre-determined time intervals and analysed with high performance liquid chromatography (HPLC) to determine the amount of API that had traversed the skin. Stratum corneum-epidermis samples and epidermis-dermis samples were prepared and left over night at 4 °C and analysed the next day with HPLC. This was done to determine the amount of API that accumulated in the epidermis-dermis and the amount of API that were left on the outer skin layers (stratum corneum-epidermis).
The results from the Franz cell diffusion studies indicated that the emulgel formulation without Pheroid™ shortened the lag time of lidocaine HCl and that the emulgel formulated with Pheroid™ shortened the lag time of prilocaine HCl, when compared to the commercial product. Pheroid™ did not enhance the flux of lidocaine HCl and prilocaine HCl into the skin. The hydrogel formulation demonstrated a high transdermal flux of prilocaine HCl due to the hydrating effect it had on the stratum corneum. The commercial product yielded high flux values for both APIs but it did not result in a high concentration of the APIs delivered to the epidermis-dermis. Pheroid™ technology did, however, enhance the epidermal-dermal delivery of lidocaine HCl and prilocaine HCl into the skin epidermis-dermis.
The stability of the emulgel formulation, Pheroid™ emulgel formulation and the hydrogel formulation was examined over a 6 month period. The formulations were stored at 25 °C/60% RH, 30 °C/60% RH and 40 °C/75% RH. The API concentration, mass, pH, zeta potential, particle size, viscosity and visual appearance for each formulation at the different storage conditions were noted and compared at month 0, 1, 2, 3 and 6 to determine if the formulations remained stable for 6 months. The results obtained from the stability study demonstrated that none of the formulations were stable for 6 months. The emulgel remained stable for the first 3 months. At 6 months, large decreases in API concentration and pH occurred which could cause a loss of anaesthetic action in the formulations. The Pheroid™ emulgel formulation did not remain stable for 6 months. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.
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Procedural pain reducing methods and pain assessment in newborns /Gradin, Maria, January 2004 (has links) (PDF)
Diss. (sammanfattning) Linköping : Linköpings universitet, 2004. / Härtill 6 uppsatser.
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Uterine or paracervical lidocaine application for pain control during intrauterine contraceptive device insertion: a meta-analysis of randomised controlled trialsPerez-Lopez, Faustino R., Martinez-Dominguez, Samuel J., Perez-Roncero, Gonzalo R., Hernandez, Adrian V. 04 May 2018 (has links)
El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Objective: Systematic review and meta-analysis to assess the effects of uterine or paracervical lidocaine application on pain control during IUD insertion. Methods: PubMed and five other electronic research databases were searched through 15 November 2017 for RCTs comparing lidocaine treatment vs. a control (placebo or no-intervention) to prevent pain during IUD insertion. Searched terms included ‘IUD insertion’, ‘lidocaine’ and ‘randomised controlled trial’. RCTs evaluating lidocaine treatment before IUD insertion without restriction of language, age and IUD type. Pain measured by visual pain scales at tenaculum placement, IUD insertion and immediate post-IUD insertion. Results of random effects meta-analyses were reported as mean differences (MDs) of visual pain scale (VPS) scores and their 95% confidence intervals (CIs). Results: Eleven RCTs (n = 1458 women) reporting paracervical lidocaine block or uterine mucosa lidocaine application before IUD insertion. Lidocaine produced lower VPS scores during tenaculum placement (MD −0.99, 95% CI: −1.73 to −0.26), IUD insertion (MD −1.26, 95% CI: −2.23 to −0.29) and immediate post-IUD insertion period (MD −1.25, 95% CI: −2.17 to −0.33). Conclusion: Lidocaine treatment was associated with modest reduction of pain during tenaculum placement and after IUD insertion. / Revisión por pares
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Eficácia anestésica da mepivacaína e da lidocaína no bloqueio mandibular em molares inferiores com pulpite irreversível / Anesthetic efficacy of mepivacaine and lidocaine in mandibular block in irreversible pulpitis molarsRenata Pieroni Visconti 20 July 2010 (has links)
Neste estudo, randomizado, duplo cego, avaliamos a eficácia anestésica em quarenta e dois pacientes, do Setor de Urgência da Faculdade de Odontologia da Universidade de São Paulo, com pulpite irreversível, que receberam mepivacaína 2% (n=21) ou lidocaína 2% (n=21) associadas à epinefrina 1:100.000 para bloqueio do nervo alveolar inferior (BNAI). O sinal subjetivo de anestesia do lábio e língua, a presença de anestesia pulpar e ausência de dor durante o procedimento de pulpectomia foram avaliados, respectivamente, por indagação ao paciente, pelo testador elétrico pulpar (TEP) e pela escala de dor verbal (VAS). Pela técnica pterigomandibular indireta das três posições, foi injetado primeiramente um tubete (1,8mL), e depois de 10 minutos, foi testada a anestesia pulpar (AP), pelo TEP, por duas leituras negativas ao estímulo máximo (80A) do aparelho. Quando não instalada a AP, um segundo tubete (mais 1,8mL) era reinjetado. Confirmada a anestesia pulpar, iniciava-se a pulpectomia. O sucesso do BNAI foi definido como a capacidade de acessar a câmara pulpar e a realização da pulpectomia sem relato de dor (VAS) pelo paciente (escore 0 ou 1), enquanto o insucesso foi caracterizado pelo incomodo/dor (escore 2 ou 3), que impedisse a continuação. Nesse caso, um terceiro e último tubete foi dado por técnicas complementares (intraligamentar ou intrapulpar) para finalizar o procedimento. Na análise estatística utilizou-se o teste Exato de Fisher e ANOVA com nível de significância fixado em 5%. Obtivemos que no grupo Mepivacaína com 1,8mL, a taxa de anestesia pulpar (AP) foi de 52% (11/21), e sucesso no BNAI de 55% (6/11); a injeção de mais 1,8mL (2º tubete) aumentou a AP para 86% (18/21) e o sucesso no BNAI para 55% (10*/18). No Grupo Lidocaína, com 1.8mL, a taxa da AP foi de 33% (7/21), o BNAI foi de 0%; com mais 1,8mL (2º tubete), a AP aumentou para 67% (14/21) e sucesso no BNAI para 14% (2*/14) (*com diferença estatística onde p0,05). A mepivacaína com volume menor proporcionou, clinicamente, maior índice de anestesia pulpar e sucesso do BNAI (pulpectomia total), e permitiu chegar mais próximo da polpa quando comparada a lidocaína. Concluímos que a mepivacaína obteve melhores resultados no sucesso do BNAI para a realização da pulpectomia em molares inferiores com pulpite irreversível. / The aim of this, double blind randomized study, was to evaluate the anesthetic efficacy of inferior alveolar nerve block (IANB) using 2% mepivacaine and 2% lidocaine both associated with adrenaline 1:100,000 in molars with irreversible pulpitis. The sample of these study consisted of forty-two healthy patients diagnosed with irreversible pulpitis actively experiencing pain. For blocking the IAN was established the following protocol: injection of one cartridge (1.8 mL) by the technique pterigomandibular of three indirect positions, expected 10 minutes and electric pulp test (EPT) Vitality Scanner®-SybronEndo, USA was accomplishment. If tooth sensitivity pain persisted another cartridge (plus 1.8 mL) was given by the same technique and the same methodology was performed. The pulpectomy was continued after the confirmation of pulpal anesthesia, which was established as the lack of response at maximum stimulation (80A) of EPT. In cases where the patient reported pain during pulpectomy even confirmed the blockage, a third cartridge was given by complementary techniques (intraligamentary or intrapulpal) to complete the endodontic procedure. The anesthetic efficacy in IANB was established when the pulpectomy was performed without report of pain and without complementation. For analysis and comparison of results we used the Fisher exact statistical test and ANOVA with significance level set at 5%. Regarding the effectiveness of the anesthetic with 1,8 mL mepivacaine, determined pulpar anesthesia (PA) was 52% (11/21), and success in IANB (pulpectomy) 55% (6/11), the most injection of 1,8 mL, increased 86% (18/21) for AP and success in IANB to 55% (10*/18). In the lidocaine group, with 1.8mL, AP rate was 33% (7/21), the IANB was 0%, with a further 1.8 mL (cartridge 2) the AP increased to 67% (14/21) and success was to IANB 14 % (2*/14), (*statistically difference p 0.05). Mepivacaine with smaller volume clinically provided a higher rate of pulpal anesthesia and most successful of IANB (pulpectomy total), allowing to reach nearest dental pulp than lidocaine. Concluded that mepivacaine performed better in success of IANB (pulpectomy) that lidocaine in molars with irreversible pulpitis
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Efeitos cardiovasculares da infiltração maxilar da articaína e lidocaína associadas à epinefrina em procedimentos restauradores / Cardiovascular effects of maxillary infiltration of articaine and lidocaine with epinephrine in restorative proceduresCarina Gisele Costa 17 December 2007 (has links)
O objetivo deste estudo foi avaliar os efeitos cardiovasculares da infiltração maxilar usando lidocaína 2% associada à epinefrina 1:100.000, articaína 4% associada à epinefrina 1:100.000 e 1:200.000 em diferentes etapas da consulta odontológica para realização de procedimento restaurador. Vinte voluntários receberam, aleatoriamente, 1,8 ml dos três anestésicos locais. A pressão arterial sistólica, diastólica e média e a freqüência cardíaca foram avaliadas pelos métodos oscilométrico e fotopletismográfico em sete etapas da consulta odontológica. A análise estatística dos parâmetros cardiovasculares através dos testes ANOVA e Tukey não mostrou diferenças significativas entre as três soluções anestésicas. Houve diferença estatisticamente significante para os parâmetros cardiovasculares entre as diferentes etapas clínicas da consulta odontológica. A variação dos parâmetros cardiovasculares é semelhante para as soluções de articaína e lidocaína associadas à epinefrina e é influenciada pelas etapas da consulta odontológica. / The aim of this study was to evaluate cardiovascular effects by maxillary infiltration using 2% lidocaine with 1:100.000 epinephrine, 4% articaine with 1:100.000 and 1:200.000 epinephrine in different stages of dental appointment for restorative procedures. Twenty healthy patients randomly received 1,8 ml of the three local anesthetics. Systolic blood pressure, average blood pressure, diastolic blood pressure and heart rate were evaluated by the oscillometric and photoplethysmograph methods in seven stages of the appointment. Statistical analysis by ANOVA and Tukey tests of cardiovascular parameters did not show significant differences between the anesthetic associations. There were significant differences for the parameters among different clinical stages of the dental appointment. The variation of cardiovascular parameters is similar for articaine and lidocaine solutions and it is influenced by the stages of the dental appointment.
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EFEITO DA LIDOCAÍNA ENDOVENOSA PERIOPERATÓRIA SOBRE A ANALGESIA E A CONCENTRAÇÃO SÉRICA DE CITOCINAS: estudo randomizado e duplo-cego / EFFECT OF ENDOVENOUS LIDOCAINE ON ANALGESIA AND SERUM CYTOKINES CONCENTRATION: randomized and double-blind trialOrtiz, Michele Purper 16 December 2014 (has links)
Postoperative pain still occurs in more than 50% of surgical procedures. It s known that
inappropriate treatment of postoperative pain can worsen patient s outcome, either for
increasing systemic surgical stress response, increasing cardiologic events, or even by
the development of chronic pain. New multimodal analgesia strategies have been
employed, based on the use of different drugs, by different administration methods and at
different times, trying to reduce the amount of opioids and, consequently, their side
effects. In this setting, continuous intravenous lidocaine used during perioperative period
has shown to be promising. This trial aimed to compare postoperative analgesia in
patients who underwent laparoscopic cholecystectomies, under general anesthesia, and
received endovenous lidocaine in comparison to a control group. Opioid consumption,
time of ileus, time to discharge and levels of interleukin 1, 6, 10, tumoral necrosis factor
and interferon gamma were also compared. Forty-four patients undergoing laparoscopic
cholecystectomies were randomly allocated in two groups. The first one received
endovenous lidocaine bolus of 1.5 mg.kg-1 followed by continuous infusion of 3 mg.kg-1
during intraoperative period until one hour after the end of the procedure. The second
one received saline, intravenously, at the same infusion rate (ml.h-1), during the same
period. It was a double-blind intervention. In the postoperative period, both groups
received dipyrone and morphine patient controlled analgesia (PCA). Pain was assessed
by VNS (Visual Numeric Scale), both at rest and when coughing at the 1st, 2nd, 4th, 12th
and 24th hour after the end of the surgery. Blood samples for cytokines measurement
were taken at the end of procedure and 24 hours later. The total morphine PCA demand,
the time for the first flatus and the length of hospital stay were also recorded and
compared. Groups were similar relating to gender (p = 0,2), age (p = 0,5), weight (p =
0,08) and length of surgery (p = 0,6). No differences were observed regarding the
intensity of postoperative pain between the groups, either at rest (p = 0,76) or when
coughing (p = 0,31), in morphine consumption (p = 0,9) and in the duration of ileus (p =
0,5) or length of hospital stay (p = 0,9). The inflammatory markers, IL-1 (p = 0,02), IL-6 (p
< 0,01), γ IFN (p < 0,01) and α TNF (p < 0,01), showed significant reduction in lidocaine
group against placebo group, except IL-10 (p = 0,01), that, because of its antiinflammatory
effects, increased its concentration. Thus, intravenous lidocaine in the
perioperative period of laparoscopic cholecystectomies was not able to reduce
postoperative pain, opioid consumption, and duration of ileus or length of hospital stay.
However, its anti-inflammatory effect was evidenced by the significant changes in the
studied cytokines. / A dor pós-operatória ainda ocorre em mais de 50% dos procedimentos cirúrgicos. Sabe-se
que o tratamento inadequado da mesma pode piorar o desfecho dos pacientes, seja através
de uma resposta sistêmica exacerbada ao estresse cirúrgico, do aumento da incidência de
eventos cardiológicos isquêmicos ou mesmo do desenvolvimento de dor crônica. Novas
estratégias de analgesia multimodal têm sido utilizadas, baseadas no uso de diferentes
fármacos, por diferentes vias de administração e em períodos distintos, tentando reduzir as
doses de opioides, e, consequentemente, seus efeitos adversos. Neste contexto, a infusão
contínua de lidocaína intravenosa no período perioperatório tem se mostrado promissora. O
objetivo principal desse estudo foi comparar o grau de analgesia pós-operatória em
pacientes submetidos a colecistectomias laparoscópicas, sob anestesia geral, que
receberam lidocaína intravenosa em relação a um grupo controle. Comparou-se, também, o
consumo de opioide, o tempo de íleo paralítico, o tempo de alta hospitalar e os níveis de
interleucinas 1, 6, 10, fator de necrose tumoral e interferon gama. Foram selecionados 44
pacientes submetidos a colecistectomias videolaparoscópicas, que foram distribuídos
aleatoriamente em dois grupos. O primeiro recebeu lidocaína endovenosa, com bolus inicial
de 1,5 mg.kg-1, seguido da infusão contínua de 3 mg.kg-1 durante o período transoperatório
até uma hora após o término do procedimento. O segundo grupo recebeu solução
fisiológica, intravenosa, nas mesmas taxas de infusão, em, durante o mesmo período de
tempo. A intervenção foi realizada de maneira duplo-cega. No pós-operatório, ambos os
grupos receberam dipirona e utilizaram analgesia controlada pelo paciente (PCA) com
morfina. A dor foi avaliada através da Escala Numérica Visual (ENV) em repouso e ao tossir
na 1ª, 2ª, 4ª, 12ª e 24ª hora após o término da cirurgia. Amostras de sangue para dosagem
de citocinas foram coletadas no final do procedimento e vinte e quatro horas após. A dose de
morfina utilizada, o tempo para passagem de flatos e o tempo de alta hospitalar também
foram registrados e comparados. Os grupos se distribuíram igualmente referente ao sexo (p
= 0,2), idade (p = 0,5), peso (p = 0,08) e tempo de cirurgia (p = 0,6). Não foram observadas
diferenças na intensidade da dor pós-operatória entre os grupos tanto em repouso (p = 0,76)
quanto ao tossir (p = 0,31), na dose total de morfina (p = 0,9) e nos tempos de íleo paralítico
(p = 0,5) e de alta hospitalar (p = 0,9). Os marcadores inflamatórios avaliados, IL-1 (p =
0,02), IL-6 (p < 0,01), IFN γ (p < 0,01) e FNT α (p < 0,01), apresentaram redução significativa
de seus níveis séricos no grupo lidocaína, com exceção da IL-10 (p = 0,01), que, por
apresentar efeito anti-inflamatório, teve sua concentração aumentada. Assim, a lidocaína
endovenosa perioperatória em colecistectomias laparoscópicas não foi capaz de reduzir a
dor pós-operatória, o consumo de opioides, o tempo de íleo paralítico e o tempo de alta
hospitalar. Entretanto, seus efeitos anti-inflamatórios foram evidenciados pelas alterações
séricas significativas das citocinas estudadas.
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Injeção peridural de lidocaína associada à xilazina ou detomidina na prevenção da dor pós-incisional em éguasSilva, Gabriel Bottini da [UNESP] 10 December 2009 (has links) (PDF)
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silva_gb_me_jabo.pdf: 1117997 bytes, checksum: 88ee7014b706d275943b075b58aba825 (MD5) / A medula espinhal tem importante papel no mecanismo de transmissão dos impulsos nervosos nociceptivos. O bloqueio desses impulsos interrompe ou minimiza a dor derivada da liberação de mediadores inflamatórios deletérios ao organismo. Assim ela tem sido sede de administração de fármacos, tanto para a realização de bloqueios anestésicos, quanto para a prevenção da dor pós-operatória. Em éguas é comum a indicação do uso da via peridural caudal para a administração de fármacos como nos casos de prolapsos uterinos e vaginais, lacerações vulvo-perineais decorrentes de distocias ou de monta natural, nos casos de pneumovagina e torções uterinas. Avaliou-se 3 grupos com 7 éguas cada, após receberem injeção peridural de 0,25 mg/kg de lidocaína associada com solução de cloreto de sódio 0,9% (GLS) ou lidocaína, na mesma dose, associada à 0,17 mg/kg de xilazina (GLX) ou 0,02 mg/kg detomidina (GLD). A avaliação considerou o perfil clínico por meio da aferição das frequências cardíaca (FC) e respiratória (f), da pressão arterial média (PA) e da avaliação da sensibilidade cutânea (SCP) com o uso de filamentos de von Frey em éguas submetidas a incisões cutâneas na região glútea. Em decorrência da diminuição da sensibilidade cutânea promovida pelos tratamentos, os valores de FC, f e de PA mantiveram-se estáveis, com pequeno declínio nos grupos GLX e GLD. As associações de lidocaína com xilazina ou com detomidina (GLX e GLD) diminuíram significativamente a sensibilidade cutânea pós-incisional (SCP) logo a partir de T15, quando comparadas ao grupo que recebeu apenas lidocaína associada á solução de cloreto de sódio 0,9% (GLS). Os três grupos apresentaram diminuíção significativa da SCP em todos os tempos após as aplicações quando comparados ao T0... / The spinal cord plays an important role the mechanism of tranmission of nociceptive nerve impulses. Blocking these impulses stop or minimize the pain derived from the release of inflammatory mediators deleterious to the body. So it has been the seat of administration of drugs, both the anesthetic blocks, and for the prevention of postoperative pain. In mares is common to indicate the use of epidural caudal to the administration of drugs as in cases of uterine prolapse and vaginal, vulvo-perineal lacerations resulting from dystocias natural mating or in cases of uterine pneumovagina and twists. We evaluated 3 groups of 7 mares each, after receiving epidural injection of 0.25 mg/kg of lidocaine mixed with sodium chloride 0.9% (GLS) or lidocaine, the same dose associated with 0.17 mg/kg xylazine (GLX) or 0.02 mg/kg detomidine (GLD). The evaluation considered the clinical profile through measurement of heart rate (HR) and respiratory rate (RR), mean arterial pressure (BP) and the evaluation of skin sensitivity (PCS) using von Frey filaments in mares undergoing skin incisions in the gluteal region. Due to the decrease in skin sensitivity promoted by the treatments, the values of FC, fe, BP remained stable, with small decline in GLD and GLX groups. Combinations of lidocaine and xylazine or detomidine (GLD and GLX) significantly decreased the sensitivity of the skin post-incision (SCP) as early as T15, compared with the group receiving only lidocaine associated with the solution of sodium chloride 0.9% (GLS). The three groups showed a significant decrease in SCP at all times after the applications when compared to T0. The GLS group showed significant differences between the values of the sides and incised not incised in the times T45 to T105, the GLX group from T60 to T1440 (except T75), and the GLD group from T90 to T1440... (Complete abstract click electronic access below)
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Injeção peridural de lidocaína associada à xilazina ou detomidina na prevenção da dor pós-incisional em éguas /Silva, Gabriel Bottini da. January 2009 (has links)
Orientador: José Antonio Marques / Banca: Carlos Augusto Araujo Valadão / Banca: Roberto Pimenta de Pádua Foz Filho / Resumo: A medula espinhal tem importante papel no mecanismo de transmissão dos impulsos nervosos nociceptivos. O bloqueio desses impulsos interrompe ou minimiza a dor derivada da liberação de mediadores inflamatórios deletérios ao organismo. Assim ela tem sido sede de administração de fármacos, tanto para a realização de bloqueios anestésicos, quanto para a prevenção da dor pós-operatória. Em éguas é comum a indicação do uso da via peridural caudal para a administração de fármacos como nos casos de prolapsos uterinos e vaginais, lacerações vulvo-perineais decorrentes de distocias ou de monta natural, nos casos de pneumovagina e torções uterinas. Avaliou-se 3 grupos com 7 éguas cada, após receberem injeção peridural de 0,25 mg/kg de lidocaína associada com solução de cloreto de sódio 0,9% (GLS) ou lidocaína, na mesma dose, associada à 0,17 mg/kg de xilazina (GLX) ou 0,02 mg/kg detomidina (GLD). A avaliação considerou o perfil clínico por meio da aferição das frequências cardíaca (FC) e respiratória (f), da pressão arterial média (PA) e da avaliação da sensibilidade cutânea (SCP) com o uso de filamentos de von Frey em éguas submetidas a incisões cutâneas na região glútea. Em decorrência da diminuição da sensibilidade cutânea promovida pelos tratamentos, os valores de FC, f e de PA mantiveram-se estáveis, com pequeno declínio nos grupos GLX e GLD. As associações de lidocaína com xilazina ou com detomidina (GLX e GLD) diminuíram significativamente a sensibilidade cutânea pós-incisional (SCP) logo a partir de T15, quando comparadas ao grupo que recebeu apenas lidocaína associada á solução de cloreto de sódio 0,9% (GLS). Os três grupos apresentaram diminuíção significativa da SCP em todos os tempos após as aplicações quando comparados ao T0 ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The spinal cord plays an important role the mechanism of tranmission of nociceptive nerve impulses. Blocking these impulses stop or minimize the pain derived from the release of inflammatory mediators deleterious to the body. So it has been the seat of administration of drugs, both the anesthetic blocks, and for the prevention of postoperative pain. In mares is common to indicate the use of epidural caudal to the administration of drugs as in cases of uterine prolapse and vaginal, vulvo-perineal lacerations resulting from dystocias natural mating or in cases of uterine pneumovagina and twists. We evaluated 3 groups of 7 mares each, after receiving epidural injection of 0.25 mg/kg of lidocaine mixed with sodium chloride 0.9% (GLS) or lidocaine, the same dose associated with 0.17 mg/kg xylazine (GLX) or 0.02 mg/kg detomidine (GLD). The evaluation considered the clinical profile through measurement of heart rate (HR) and respiratory rate (RR), mean arterial pressure (BP) and the evaluation of skin sensitivity (PCS) using von Frey filaments in mares undergoing skin incisions in the gluteal region. Due to the decrease in skin sensitivity promoted by the treatments, the values of FC, fe, BP remained stable, with small decline in GLD and GLX groups. Combinations of lidocaine and xylazine or detomidine (GLD and GLX) significantly decreased the sensitivity of the skin post-incision (SCP) as early as T15, compared with the group receiving only lidocaine associated with the solution of sodium chloride 0.9% (GLS). The three groups showed a significant decrease in SCP at all times after the applications when compared to T0. The GLS group showed significant differences between the values of the sides and incised not incised in the times T45 to T105, the GLX group from T60 to T1440 (except T75), and the GLD group from T90 to T1440... (Complete abstract click electronic access below) / Mestre
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Comparação da articaína e lidocaína no bloqueio do nervo alveolar inferior / Comparison of articaine and lidocaine in alveolar nerve block lowerMarcelo Siviero 30 January 2009 (has links)
O objetivo dessa pesquisa foi avaliar o tempo de latência e duração pulpar anestésica da dose de 1,8ml das seguintes soluções anestésicas locais: cloridrato de articaína 4% associado à epinefrina 1:100.000 (ART 100) e 1:200.000 (ART 200) e cloridrato de lidocaína 2% associado à epinefrina 1:100.000 (LIDO 100) no bloqueio convencional do nervo alveolar inferior. A amostra do experimento consistiu de vinte pacientes normorreativos, submetidos a três consultas para tratamento restaurador de baixa complexidade em três dentes posteriores inferiores. Os períodos de latência e duração da anestesia local na polpa dentária foram monitorados com um estimulador pulpar elétrico (Vitality Scanner Model 2006®-SybronEndo, CA, EUA). Para análise e comparação dos resultados da latência e duração pulpar das três soluções anestésicas locais foi utilizado o teste paramétrico ANOVA e o teste auxiliar de Bonferroni com nível de significância fixado em 5% (p<0,05). Em relação ao período de latência pulpar não houve diferença estatisticamente significante entre nenhuma das três soluções anestésicas locais utilizadas (p > 0,05). Já em relação ao período de duração pulpar houve diferença estatisticamente significante entre ART 100 e LIDO 100 (p=0,000) e entre ART 200 e LIDO 100 (p=0,000). Portanto, a latência das duas soluções de articaína foram similares à solução de lidocaína, mas ambas apresentaram duração de ação anestésica maior do que a solução de lidocaína. / The aim of this study was to evaluate the time of onset and duration of pulp anesthetic dose of 1.8 ml of local anesthetic solutions following: 4% hydrochloride articaine associated with epinephrine 1:100.000 (ART 100) and 1:200.000 (ART 200) and 2% hydrochloride of lidocaine associated with epinephrine 1:100.000 (LIDO 100) in alveolar nerve block lower. The sample of the experiment consisted of twenty healthy patients, underwent three appointments for restorative treatment of low complexity in three subsequent lower teeth. The periods of onset and duration of local anesthetic in dental pulp were monitored with an electric stimulator pulp (Vitality Scanner®, Model 2006 - SybronEndo, CA, USA). To analyze and compare the results of onset and duration of the three pulp solutions local anesthetic was used parametric ANOVA test and the test of Bonferroni help with significance level set at 5% (p < 0.05). For the period of onset there was no statistically significant difference between any of the three approaches used local anesthetic (p> 0.05). Already in relation to the duration of pulp statistically significant difference between ART 100 and LIDO 100 (p = 0000) and between ART 200 and LIDO 100 (p = 0000). Therefore, the onset of the two solutions of articaine were similar to the solution of lidocaine, but both showed duration of anesthetic action superior to the solution of lidocaine.
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Lidocaina lipossomal produzida em processo escalonavel : formulação, caracterização e testes biologicos / Liposomal lidocaine prepared in a scale-up procedure : formulation, characterization and biological testsAlmeida, Ana Claudia Pedreira de 23 June 2008 (has links)
Orientador: Eneida de Paula / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-11T08:29:18Z (GMT). No. of bitstreams: 1
Almeida_AnaClaudiaPedreirade_D.pdf: 2120861 bytes, checksum: ce2b043fb38d0b927ee7a899b2da40ae (MD5)
Previous issue date: 2008 / Resumo: Anestésicos locais se caracterizam pela capacidade de abolir a dor sem a perda da consciência; contudo, são moléculas pequenas facilmente redistribuídas do sítio de injeção, limitando a duração da anestesia. Uma maneira de prolongar a anestesia é encapsular os anestésicos locais com sistemas carreadores como lipossomas, que permaneçam no sítio de injeção por um tempo maior, liberando o anestésico gradualmente e diminuindo sua toxicidade sistêmica. Este trabalho teve por finalidade caracterizar físico-químicamente uma nova formulação de lidocaína lipossomal, preparada por um processo escalonável; quanto à estabilidade e toxicidade local e avaliar a eficácia da formulação in vivo, quanto ao bloqueio sensorial e efeito sobre o sistema cardiovascular, em modelos animais, em comparação com preparações comerciais de LDC, associadas ou não a vasoconstritores. Partículas sólidas foram preparadas misturando-se fosfatidilcolina de soja hidrogenada, colesterol e manitol; após secagem em spray-dryer as partículas sólidas foram ressuspensas em tampão, a pH 7,4. A LDC foi incorporada na concentração de 2%. Análises por espalhamento de luz quase elástico revelaram uma população principal de lipossomas com 292,5 nm (100 %), cujo tamanho diminuiu para 227,0 nm após a incorporação da LDC. O coeficiente de partição determinado para o anestésico neste sistema foi de 23,5 ± 7,9. Experimentos de diálise mostraram que a encapsulação nos lipossomas reduziu a taxa de liberação da LDC em relação à LDC livre, o que pode levar a um prolongamento do efeito anestésico. O processo de esterilização por calor levou a um aumento significativo na peroxidação lipídica, porém os níveis de peróxido foram inferiores a 2nM por 10 meses após a preparação. Análises de espalhamento de luz indicaram que o tamanho dos lipossomas manteve-se estável por até 8 meses, a 4oC. Os ensaios in vitro, em cultura de fibroblastos 3T3, demonstraram que a encapsulação nos lipossomas não alterou de forma significativa a toxicidade da LDC em relação à LDC livre, mas apresentou menor citotoxicidade que a lidocaína associada ao vasoconstritor. Nos ensaios in vivo, o efeito anestésico da formulação de lidocaína lipossomal foi avaliado em relação à LDC livre e LDC com vasoconstritor, nas mesmas concentrações, pelo teste de bloqueio do nervo infraorbital, em ratos. Apesar do efeito anestésico da lidocaína lipossomal 2% não ser tão prolongado quanto o da lidocaína comercial associada à epinefrina, esta se mostrou vantajosa, pois aumentou em 67% o efeito anestésico total obtido, em relação à LDC livre 2% e teve efeito equivalente ao da LDC livre 3% (p<0,05). A cardiotoxicidade foi avaliada através do eletrocardiograma (ECG), medindo-se a pressão arterial média (PAM) e a freqüência cardíaca (FC), em ratos. Os resultados mostraram que não houve alterações no ECG, com redução na FC e queda na PAM que foi 52% menor para o grupo da LDC lipossomal em relação ao uso da LDC livre (p<0,05). Em conclusão, a nova formulação de lidocaína lipossomal aumentou a duração do bloqueio nervoso sensorial com menor cardiotoxicidade, podendo promover benefícios clínicos com uma margem de segurança maior, tornando-se uma formulação promissora na busca de anestésicos mais seguros e potentes / Abstract: Local anesthetics are characterized by their ability to suppress pain without losing awareness; however, these small molecules are quickly released from the site of injection, limiting the duration of anesthesia. One interesting approach to prolong anesthesia is to encapsulate local anesthetics with carrier systems as liposomes that will remain at the site of injection, gradually releasing the anesthetic and reducing its systemic toxicity. In this study we have performed the physicochemical characterization of a novel liposomal lidocaine formulation, prepared with a spray-dryer scale-up procedure, regarding its stability and local toxicity. The In vivo evaluation of the sensorial blockade and effect on the cardiovascular system caused by the formulation was essayed in animal models, in comparison to the commercially available preparation of LDC, associated or not with vasoconstrictors. Solid lipid particles were prepared mixing hydrogenated soybean phosphatidylcholine, cholesterol and mannitol; after the spray-drying process the particles were suspended in buffer at 7.4. LDC was incorporated in a 2% concentration. Laser light-scattering analysis showed a main liposome population with 292.5 nm (100%), which size slightly decreased (227.0 nm) after LDC incorporation. The partition coefficient of LDC in the system was determined as 23.5 ± 7.9. Dialysis experiments showed that encapsulation into liposomes reduced the release rate of LDC in relation to free LDC, what can take to a longer anesthetic effect. The sterilization process significantly increased lipid peroxidation, but the levels were less than 2nM up to 10 months after preparation. Light scattering analysis indicated that the size of the vesicles remained stable up to 8 months, at 4oC. In vitro essays with 3T3 fybroblasts demonstrated that encapsulation into liposomes did not significantly change the LDC toxicity in relation to free LDC, but diminished the citotoxicity in relation to the vasoconstrictor-associated LDC. In vivo essays the anesthetic effect of the liposomal lidocaine formulation was compared to that of free LDC and vasoconstrictor-associated LDC, at the same concentrations, through the infraorbital nerve blockade test in rats. Although the effect of liposomal lidocaine 2% was not comparable to that obained with lidocaine plus epinefrine, that formulation was found to be very interesting since it increased 67% the anesthetic effect in relation to free lidocaine at 2% and it was equipotent to free lidocaine 3% (p<0.05). Cardiotoxicity was evaluated through electrocardiograms (ECG), measuring the average arterial pressure (AAP) and heart rate (HR), in rats. Results showed no alterations in the ECG, but a decrease in the HR and a 52% reduction in the AAP in the liposome LDC group in comparison to the animals treated with free LDC were shown. In conclusion, the novel liposome lidocaine formulation presented here increased the sensorial nervous blockade duration and decreased the cardiotoxicity, promoting clinic benefits that include a higher drug-safety becoming a promising formulation in the search for safer and more potent anesthetics / Doutorado / Bioquimica / Doutor em Biologia Funcional e Molecular
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