An alternative analgesic to morphine is methadone, which is used to control chronic pain and is used in opioid rehabilitation treatment programs due to methadone having a long half-life and being relatively inexpensive as compared to extended-release forms of morphine. Despite its benefits, methadone accumulates in adipose tissue due to being lipophilic, binds strongly to plasma proteins, and is metabolized in the liver by the cytochrome P450 system causing methadone levels to be variable and subject to influence according to the individual body compositions and concurrent use of cytochrome P450 inhibitors. In addition to methadone being able to cause both respiratory and central nervous system depression, methadone can also prolong the QT interval and cause potentially life-threatening arrhythmias including torsades de pointes. The susceptibility of unintentional overdosing of methadone due to its varied pharmacologic properties and potentially fatal induction of arrhythmias may cause the risks of methadone use to outweigh its benefits and therefore must be closely monitored.

No description available.

MSc (Med),Dept of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand / Pain is the net effect of multidimensional mechanisms that engage most parts of the central nervous system (CNS) and the treatment of pain is one of the key challenges in clinical medicine (Le Bars et al., 2001; Miranda et al., 2008). Polypharmacy is seen as a barrier to analgesic treatment compliance, signifying the necessity for the development of fixed dose combinations (FDCs), which allow the number of tablets administered to be reduced, with no associated loss in efficacy or increase in the prevalence of side effects (Torres Morera, 2004). FDCs of analgesic drugs with differing mechanisms of nociceptive modulation offer benefits including synergistic analgesic effects, where the individual agents act in a greater than additive manner, and a reduced occurrence of side-effects (Raffa, 2001; Camu, 2002). This study aimed at producing a novel, rate-modulated, fixed-dose analgesic formulation for the treatment of mild to moderate pain. The fixed-dose combination (FDC) rationale of paracetamol (PC), tramadol hydrochloride (TM) and diclofenac potassium (DC) takes advantage of previously reported analgesic synergy of PC and TM as well as extending the analgesic paradigm with the addition of the anti-inflammatory component, DC. The study involved the development of a triple-layered tablet delivery system with the desired release characteristics of approximately 60% of the PC and TM being made available within 2 hours to provide an initial pain relief effect and then sustained zero-order release of DC over a period of 24 hours to combat the on-going effects of any underlying inflammatory conditions. The triple-layered tablet delivery system would thus provide both rapid onset of pain relief as well as potentially address an underlying inflammatory cause. The design of a novel triple-layered tablet allowed for the desired release characteristics to be attained. During initial development work on the polymeric matrix it was discovered that only when combined with the optimized ratio of the release retarding polymer polyethylene oxide (PEO) in combination with electrolytic-crosslinking activity, provided by the biopolymer sodium alginate and zinc gluconate, could the 24 hour zero-order release of DC be attained. It was also necessary for this polymeric matrix to be bordered on both sides by the cellulosic polymers containing PC and TM. Thus the application of multi-layered tableting technology in the form of a triple-layered tablet were capable of attaining the rate-modulated release objectives set out in the study. The induced barriers provided by the three layers also served to physically separate TM and DC, reducing the likelihood of the bioavailability-diminishing interaction noted in United States Patent 6,558,701 and detected in the DSC analysis performed as part of this study. The designed system provided significant flexibility in modulation of release kinetics for drugs of varying solubility. The suitability of the designed triple-layered tablet delivery system was confirmed by a Design of Experiments (DoE) statistical evaluation, which revealed that Formulation F4 related closest to the desired more immediate release for PC and TM and the zero-order kinetics for DC. The results were confirmed by comparing Formulation F4 to typical release kinetic mechanisms described by Noyes-Whitney, Higuchi, Power Law, Pappas-Sahlin and Hopfenberg. Using f1 and f2 fit factors Formulation F4 compared favourably to each of the criteria defined for these kinetic models. The Ultra Performance Liquid Chromatographic (UPLC) assay method developed displayed superior resolution of the active pharmaceutical ingredient (API) combinations and the linearity plots produced indicated that the method was sufficiently sensitive to detect the concentrations of each API over the concentration ranges studied. The method was successfully validated and hence appropriate to simultaneously detect the three APIs as well as 4-aminophenol, the degradation product related to PC. Textural profile analysis in the form of swelling as well as matrix hardness analysis revealed that an increase in the penetration distance was associated with an increase in hydration time of the tablet and also an increase in gel layer thickness. The swelling complexities observed in the delivery system in terms of both the PEO, crosslinking sodium alginate and both cellulose polymers as well as the actuality of the three layers of the tablet swelling simultaneously suggests further intricacies involved in the release kinetics of the three drugs from this tablet configuration. Modified release dosage forms, such as the one developed in this study, have gained widespread importance in recent years and offer many advantages including flexible release kinetics and improved therapy and patient compliance.

Copaifera langsdorffii Desf. é conhecida popularmente como \"copaíba\", sendo encontrada nas regiões norte e nordeste do Brasil. Nesta tese reportam-se o estudo fitoquímico das folhas de C. langsdorffii, por meio do fracionamento de seu extrato hidroalcoólico, o isolamento e a purificação de seus metabólitos secundários majoritários, a biotransformação do epóxido do ácido caurenóico, bem como a avaliação das atividades analgésica e anti-inflamatória do extrato e compostos isolados. Para avaliação do perfil cromatográfico, o extrato hidroalcoólico das folhas (Cop) foi particionado em hexano, diclorometano, acetato de etila, n-butanol e água. Com o uso de filtração em gel, Cromatografia Contra Corrente e CLAE preparativa foram isolados os compostos quercetina-3-O-?-L-ramnopiranosídeo (quercitrina), canferol-3-O-?-L-ramnopiranosídeo (afzelina), bem como os ácidos 4\',4\'\'-dimetóxi-4,5-di-O-galoilquínico e 4-(4\'\'-metóxi galoil)-3,5-di-O-galoilquínico. O ácido caurenóico e o caurenol foram isolados em coluna de gel de sílica a partir da fração em acetato de etila. O ácido caurenóico foi submetido a epoxidação com ácido 3-cloroperbenzóico e foi submetido à biotransformação pelo fungo Beauveria sulfurenscens em meio sintético. A biotransformação do epóxido do ácido caurenóico forneceu o ácido 7?,17-diidroxi-ent-caur-15-en-19-oico, até então desconhecido, bem como o ácido 7?,17-diidroxi-16?-ent-cauran-19-oico, o ácido 7?,17-diidroxi-16?-ent-cauran-19-oico, o ácido 9?,16?,17-triidroxi-ent-cauran-19-oico e o ácido 16?,17-diidroxi-ent-cauran-19-óico. Cop e caurenol reduziram a inflamação induzida por ácido acético com máxima inibição de 40,3 e 53,6%, respectivamente. Na segunda fase do ensaio de formalina foi observada redução de 54,5 e 64,6%, respectivamente. A resposta inflamatória observada por carragenina e dextrana mostrou máxima redução de 52,3 e 43,6% para Cop e de 64,3 e 80% para caurenol, respectivamente. Cop e caurenol reduziram a produção de NO estimulada por LPS e aumentaram a liberação de TNF-?, mas não modularam a expressão de IL-6 e IL-10. Portanto, caurenol está envolvido na atividade antiedematogênica do extrato. Já a quercitrina e a afzelina não foram ativas nos protocolos utilizados. Cop e caurenol não alteraram a primeira fase do ensaio de formalina, a latência em placa quente, o desempenho motor dos animais e a migração celular. Concluiu-se que Cop e caurenol possuem atividade antiedematogênica atuando em sítios periféricos, contudo essa propriedade não está associada com a regulação da migração celular, TNF-?, IL-6 e IL-10. / Copaifera langsdorffii Desf., known as \"copaiba\", is found in the northern and northeastern of Brazil. This thesis reports the phytochemical study of C. langsdorffii leaves, through its hydroalcoholic extract (Cop) fractionation, isolation and purification of its major secondary metabolites, the biotransformation of kaurenoic acid epoxide, as well the evaluation of the analgesic and anti-inflammatory activities of the extract and isolated compounds. For the evaluation of the chromatographic profile, the extract was partitioned into hexane, dichloromethane, ethyl acetate, n-butanol and water fractions. With the use of gel filtration chromatography, counter current chromatography and preparative HPLC, quercetin-3-O-?-L-rhamnopyranoside (quercitrin), kaempferol-3-O-?-L-rhamnopyranoside (afzelin), 4\'- 4\'\'-dimethoxy-4 ,5-di-O-galloylquinic acid and 4-(4-methoxy galloyl\'\')-3,5-di-O-galloylquinic were isolated. The epoxidation of kaurenoic acid was performed with 3-chloroperbenzoic acid and it was submitted to biotransformation by the fungus Beauveria sulfurenscens in synthetic medium. Biotransformation of kaurenoic acid epoxide furnished the unknown compound 7?,17-dihydroxy-ent-kaur-15-en-19-oic acid and the compounds 7?,17-dihydroxy-16?-ent-kauran-19-oic acid, 7?,17-dihydroxy-16?-ent-kauran-19-oic acid, 9?, 16?,17-trihydroxy-ent-kauran-19-oic acid and 16?,17-dihydroxy-19-ent-kauran-oic acid. Cop and kaurenol reduced the inflammation induced by acetic acid in mice with a maximal inhibition of 40.3 and 53.6%, respectively. The second phase in the formalin test in mice showed maximal reduction of 54.5 and 64.6%, respectively. The inflammatory responses induced by both carrageenan and dextran in rats showed maximal reduction of 52.3 and 43.6 % for Cop, as well as 64.3% and 80.0% for kaurenol, respectively. Cop and kaurenol reduced the NO production stimulated by LPS in a dose-dependent manner, and increased the release of TNF-?, but did not regulate IL-6 and IL-10. Therefore, kaurenol is involved in the extract antiedematogenic activity of the extract, whereas quercitrin and afzelin were not active in the used protocols. Cop and kaurenol did not alter the formalin first phase, hot-plate latency, motor performance or cell migration. The obtained results show that C. langsdorffi extract and kaurenol possess antiedematogenic properties acting on peripheral sites, but these properties are not associated with cell migration, TNF-?, IL-6 or IL-10 regulation.

Introdução: A literatura sugere que o medo da dependência de opióides é uma barreira para o alívio da dor, especialmente quando há suspeita de uso desses fármacos. No entanto, essa hipótese carece de testes empíricos. Objetivos: Comparar a conduta de profissionais de enfermagem na administração de analgésicos opióides e não opióides, quando há ou não suspeita de que o paciente seja usuário de drogas; identificar a prevalência de pacientes com suspeita de uso de drogas e conhecer as características dos pacientes que os profissionais de enfermagem consideram como sugestivas de uso de drogas. Método Estudo transversal com pacientes e profissionais de enfermagem (auxiliares e técnicos). Foram incluídos 507 pacientes com trauma ortopédico e prescrição de analgésico opióide, internados em quatro hospitais de Londrina, Paraná, entre fevereiro de 2011 a março de 2012, e 199 profissionais responsáveis pela administração de medicamentos a esses pacientes. Cada paciente recebeu a avaliação de três profissionais e considerou-se paciente suspeito aquele indicado por pelo menos um profissional. O desfechos principais foram a 1) quantidade administrada de analgésicos opióides e não opióides prescritos em regime se necessário e em horário fixo nas últimas 24 horas; 2) prevalência de pacientes suspeitos de uso de drogas; 3) condutas dos profissionais frente à solicitação do opióide; 4) Características dos pacientes que os profissionais consideram sugestivas de uso de drogas. Nas análises utilizaram-se os testes de Qui quadrado, Fisher e Mann-Whitney, e nível de significância de 5%. Resultados: A prevalência de pacientes suspeitos foi de 6,86%, maior em homens (p<0.036) e jovens (p<0,001). Os pacientes suspeitos receberam mais opióides se necessário (p=0,037) e até 30% da dose máxima possível, contra até 20% para os não suspeitos. A administração entre suspeitos e não suspeitos não diferiu quanto aos opióides prescritos em horário fixo, no entanto, deixou-se de administrar 10% da dose para ambos os grupos. Entre os profissionais entrevistados, 75,6% relataram que mantêm a analgesia com opióide, mesmo quando há suspeita de o paciente ser usuário de droga, mas 28,9% deles disseram tentar reduzir a dose nesses casos. As características dos pacientes mais frequentemente consideradas pelos profissionais como sugestivas de uso de drogas pertenciam à categoria consequências emocionais/físicas/sociais e sinais de abstinência (70,6%) e insistência pelo opióide (55,9%), mais do que a aparência pessoal (0,0%). Conclusão: A prevalência de suspeitos foi semelhante a estudos realizados em departamentos de emergência, sugerindo que os auxiliares e técnicos de enfermagem foram cuidadosos na estimativa de suspeição. Os resultados obtidos contrariam a literatura, pois indicaram que os suspeitos de serem usuários de droga receberam mais analgésicos opióides. Assumindo-se a premissa de que os profissionais identificaram corretamente os usuários de drogas, pode-se explicar o maior recebimento de opióide pelos suspeitos, pelas características comportamentais e emocionais: maior inquietude, insistência verbal e talvez menor alívio da dor, pois usuários de droga podem desenvolver tolerância. A administração de analgésicos, especialmente em esquema se necessário, é uma decisão importante da enfermagem que pode contribuir para o alívio da dor, daí a importância de entender as motivações que influenciam os profissionais nessa decisão. / Introduction: The literature suggests that the fear of getting addicted to opiods can be a barrier to adequate pain relief, especially when there is a suspicious of drug use. However, this hypothesis needs to be tested empirically. Objectives: Compare the conduct of nursing professionals in administering analgesics when there is the suspicion that the patient is a drug user; identify the prevalence of patients with the suspicious of drugs use and knowing the characteristics of patients that nursing professionals consider as indicators of drug use. Method: Transversal study with patients and nursing professionals (aides and technicians). The study included 507 patients with orthopedics trauma to whom opiod analgesics were prescribed. They were admitted to four hospitals in Londrina, Paraná, Brazil, between February 2011 and 2012. Patients were seen by 199 professionals responsible for administering the medications. Each patient was evaluated by three professionals regarding drug use suspicion. The patient was classified as suspect when indicated by at least one of these professionals. The evaluation included 1) amount of opioid analgesics prescribed under the if necessary regime and at fixed times; 2) prevalence of patients being suspected of drug use and 3) professionals conduct when dealing with opioid prescriptions in the last 24 hours. The analysis used Chi Square, Fisher and Mann- Whitney tests at 5% of level of significance. Results: The prevalence of suspect patients was 6.86%, greater in men (p<0.036) and young people (p<0,001). When comparing the group of suspects with the group of non-suspects, the suspect patients received more opioids under the if needed regime (p=0.037) and up to 30% of the possible maximum dosage against 20% for the non suspects. There was no difference between suspects and non suspects regarding the administration of opioid analgesics prescribed as if necessary; however, 10% of the dosage was not administered to both groups. Among the interviewed nursing aides and technicians, 75,6% reported that they maintain analgesia with opioid even when there was a suspicion that the patient is a drug user; however, 28,9% said they tried to reduce the dosage in these cases. The patients characteristics most often considered by professionals as suggestive of drug use belonged to the emotional/physical/social consequences and withdrawal signs category (70,6%) and insistence by the opioid (55,9%), more than personal appearance (0,0%). Conclusion: The prevalence of suspects was similar to studies performed in emergency departments, suggesting that nursing aides and technicians were careful in estimating suspicion. The results contradict those mentioned in the literature, since they indicate that drug users suspects received more opioid analgesics. By accepting the assumption that nursing aides and technicians have identified illicit drug users correctly, the greater number of opioid administration by the suspects can be explained based on the behavioral and emotional characteristics of this group: greater restlessness, verbal insistence and perhaps less pain relief, since drug users may develop tolerance to certain drugs. Whether or not to administer analgesics, especially those with the if necessary regime, is an important decision for the nursing staff, since they can contribute to an adequate pain relief, thus the importance of understanding the motivations that lead professionals to take this decision.

Assegurar o bem-estar dos animais de laboratório e evitar a dor e o sofrimento desnecessários são as principais considerações na experimentação. Por isso, a investigação em busca de novos protocolos anestésicos que garantam um mínimo ou nulo desconforto dos animais tem-se convertido num tema prioritário. Neste estudo realizou-se a comparação do efeito da combinação de xilazina (X) e ketamina (K) com acepromazina (A) e opióides [metadona (Me), morfina (Mo) e tramadol (T)] com a finalidade de avaliar sua influência nos parâmetros fisiológicos de ratos de laboratório, para ambos os sexos, bem como seu poder analgésico e o efeito da oxigenação sobre os mesmos. A associação XKA para ratos machos e fêmeas e a associação XKMe para fêmeas foram as mais seguras e eficazes para procedimentos anestésicos. Porém, os resultados do teste de formalina com a medição da vocalização ultrassônica (VUS) sugerem que o protocolo de XKA tem um poder analgésico baixo, não sendo indicado para procedimentos que possam gerar dor moderada ou severa. Todas as associações anestésicas tiveram efeitos importantes como diurese, manutenção dos olhos abertos e hiperglicemia, os quais devem ser considerados quando possam influenciar nos resultados experimentais. Também, se conseguiu demonstrar que a oxigenação melhora a saturação de oxigênio (SO2) e os valores da pressão parcial de oxigênio (pO2) confirmando que sua utilização deveria ser sempre parte dos procedimentos experimentais com anestesia injetável para evitar a hipoxemia. Não obstante, observou-se uma acidose respiratória por aumento da pressão parcial do CO2 (pCO2) e diminuição do pH, cuja causa se relacionou à hipoventilação por depressão respiratória e acúmulo de CO2 durante o transcorrer da anestesia. Tal situação demonstra a necessidade de oxigenar os animais desde a indução da anestesia e de administrar medicamentos para reverter a depressão respiratória como a naloxona, bem como utilizar animais que não apresentem nenhum tipo de comprometimento respiratório. Portanto, a inclusão de analgesia e a oxigenação nos protocolos anestésicos injetáveis devem ser utilizadas de forma rotineira garantindo a mínima presença de dor e, com isso, resultados mais confiáveis nos procedimentos experimentais. / Ensuring the wellbeing of laboratory animals and avoiding unnecessary pain and suffering is one of the main considerations in experimentation. Therefore, the investigation of new anesthetic protocols that guarantee a minimum or null discomfort of the animals has become a priority theme. In this study, it was made an evaluation of the effect of the combination of xylazine (X) and ketamine (K) with acepromazina (A) and opioids [methadone (Me), morphine (Mo) e tramadol (T)] with the purpose of comparing their influence on the physiological parameters of laboratory rats, for both sexes, and evaluating their analgesic power and the effect of the oxygenation on them. The XKA protocol for male and females rats and the XKMe protocol for females were the safest and most effective for anesthetic procedures. However, the results of the formalin test with the measurement of the ultrasonic vocalization (VUS) suggest that the XKA protocol had a low analgesic power, and it is not indicated for procedures that can generate moderate or severe pain. All anesthetic protocols had important effects as diuresis, maintenance of open eyes, and hyperglycemia; these effects should be considered when they could influence in the experimental results. It was demonstrated that oxygenation improves oxygen saturation (SO2) and oxygen partial pressure (pO2) confirming that its use should be considered in the experimental procedures with injectable anesthesia to avoid hypoxemia. Nevertheless, a respiratory acidosis was observed due to the increase in partial pressure of CO2 (pCO2) and the decrease in pH, that could be caused for the hypoventilation due to respiratory depression and CO2 accumulation during the course of anesthesia. This leads to consider the need to pre-oxygenate animals from induction, to use drugs to reverse respiratory depression such as naloxone, and to work with animals that are not respiratory compromised. Therefore the inclusion of analgesia and oxygenation in anesthesia protocols should begin to be used routinely ensuring minimal presence of pain and thus more reliable results in the experimental procedures.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / No presente estudo, o Topiramato (TP) foi avaliado em modelos de dor aguda e de dor neuropÃtica diabÃtica. Camundongos Swiss machos foram utilizados nos testes de nocicepÃÃo aguda (formalina, placa quente e capsaicina) e ratos Wistar machos no teste de dor neuropÃtica (filamentos de von Frey). No teste da formalina (2 %; 20 ÂL/i.pl.), foi quantificado o tempo que o animal lambia a pata que recebeu o estÃmulo durante 0-10 min (fase 01) e 20-40 min (fase 02). Os resultados mostraram uma reduÃÃo na segunda fase (***p<0,001) nas trÃs doses utilizadas do TP, enquanto que apenas a maior dose mostrou efeito na primeira fase do teste (***p<0,001). O efeito do TP (80 mg/Kg) foi revertido pela naloxona 2 mg/Kg na segunda fase do teste da formalina , mas nÃo pela glibenclamida 3mg/Kg, ciproeptadina 5 mg/Kg e ondansetrona 0,5 mg/Kg quando comparado com o controle em ambas as fases. No teste da placa quente (52Â) foi verificada a reaÃÃo do camundongo ao estÃmulo tÃrmico onde o animal responde tentando pular ou lamber uma de suas patas traseiras. Os animais foram submetidos a placa aos 00, 30, 60, 120 e 240 min apÃs os tratamentos e comparou-se os grupos que receberam TP nas diferentes doses ( 20, 40 e 80 mg/Kg) e o grupo controle. Nesse modelo, TP demonstrou atividade aos 90 e 120min (**p<0,01; ***p<0,001) apenas na maior dose utilizada (80 mg/Kg). Em outro protocolo, os animais receberam capsaicina (20 ÂL, 2 Âg/ i.pl), sendo quantificado o tempo durante 5 min que estes lamberam ou morderam a pata estimulada, com comparaÃÃo posterior entre os grupos NÃo se verificou efeito significativo de TP em todas as doses utilizadas quando comparado com o controle. Para avaliaÃÃo da aÃÃo antinociceptiva em dor neuropÃtica, os animais foram inicialmente induzidos a diabetes com estreptozotocina 40 mg/Kg i.p e apÃs trinta dias foram submetidos ao teste com filamentos de von. NÃo se verificou efeito significativo do TP nas doses utilizadas quando comparado com o controle. O TP nÃo alterou a freqÃÃncia de locomoÃÃo dos animais no teste do campo aberto e no teste do Rota rod e nÃo aumentou o nÃmero de quedas nem diminuiu o tempo de permanÃncia na barra giratÃria, sugerindo que o TP nÃo exerce sua atividade antinociceptiva por aÃÃo depressora ou relaxante muscular. Em conclusÃo, a partir desses resultados podemos sugerir que o TP apresenta efeito antinociceptivo frente a diferentes estÃmulos de dor aguda, mas nÃo na dor neuropÃtica diabÃtica. O efeito analgÃsico nos testes de dor aguda, provavelmente envolve sistema opiÃide, porÃm nÃo os canais de potÃssio sensÃveis ao ATP e sistema serotoninÃrgico / In the present study, Topiramate (TP) was evaluated in acute pain and diabetic neuropathic animal models. Male Swiss mice were used in the tests of acute nocicepcion (formalin, hot plat and capsaicin) e male Wistar rats in the neuropathic pain test (filaments of von Frey). In the formalin test (2%, 20 ÂL/i.pl), it was measured the time spent by the animal licking the left hind paw which received the stimulation during 0-10 min (phase 01) and 20-40 min (phase 02).The results showed a reduction of the second phase (*** p<0.001) in the three doses used of TP while only the biggest dose showed effect in the first stage of test (*** p< 0.001). The TP effect (80 mg/Kg) was reverted by naloxone 2 mg/kg in the second phase of the test of the formalin, but not for glibenclamide 3 mg/kg, cyproeptadine 5 mg/kg and ondansetron 0.5 mg/kg when compared to control in both phases. In the hot plate test (52Â) was analysed the reaction of the mouse to the thermal stimulation where the animal respond tryning to jump or to lick one of its brack legs. The animals had been submitted the plate to 00, 30, 60 and 120 min after the treatments and compared the groups that had received TP in the different doses (20,40 e 80 mg/kg). The results showed, TP demonstrated activity to 90 and 120 min (**p < 0.01; *** p < 0.001) only in the biggest dose used (80mg/kg). In another protocol, the animals received capsaicin (20 ÂL/2Âg/i.pl), but the results ere not significant. For evaluations of the antinociceceptive action in neuropathic pain, the animals had been initially induced diabetes with streptozotocine 40 mg/Kg i.p. and after thirty days had been submitted to the test with filaments of von Frey. No significant effect of TP was observed in all doses used when compared with the controls. TP did not modify the frequency of locomotion of the animals in the open field and presented no effect in the Rota rod test suggesting that the TP does not exert its analgesic effect by depressive actions or relaxant muscular activity. In conclusion, the results may suggest that TP presents antinociceptive effect front the different stimulations of acute pain, but not in diabetic neuropathic pain. The analgesic effect in acute pain, probably involves system opioid, and seems do not involve potassium canals or serotoninergic system

Assegurar o bem-estar dos animais de laboratório e evitar a dor e o sofrimento desnecessários são as principais considerações na experimentação. Por isso, a investigação em busca de novos protocolos anestésicos que garantam um mínimo ou nulo desconforto dos animais tem-se convertido num tema prioritário. Neste estudo realizou-se a comparação do efeito da combinação de xilazina (X) e ketamina (K) com acepromazina (A) e opióides [metadona (Me), morfina (Mo) e tramadol (T)] com a finalidade de avaliar sua influência nos parâmetros fisiológicos de ratos de laboratório, para ambos os sexos, bem como seu poder analgésico e o efeito da oxigenação sobre os mesmos. A associação XKA para ratos machos e fêmeas e a associação XKMe para fêmeas foram as mais seguras e eficazes para procedimentos anestésicos. Porém, os resultados do teste de formalina com a medição da vocalização ultrassônica (VUS) sugerem que o protocolo de XKA tem um poder analgésico baixo, não sendo indicado para procedimentos que possam gerar dor moderada ou severa. Todas as associações anestésicas tiveram efeitos importantes como diurese, manutenção dos olhos abertos e hiperglicemia, os quais devem ser considerados quando possam influenciar nos resultados experimentais. Também, se conseguiu demonstrar que a oxigenação melhora a saturação de oxigênio (SO2) e os valores da pressão parcial de oxigênio (pO2) confirmando que sua utilização deveria ser sempre parte dos procedimentos experimentais com anestesia injetável para evitar a hipoxemia. Não obstante, observou-se uma acidose respiratória por aumento da pressão parcial do CO2 (pCO2) e diminuição do pH, cuja causa se relacionou à hipoventilação por depressão respiratória e acúmulo de CO2 durante o transcorrer da anestesia. Tal situação demonstra a necessidade de oxigenar os animais desde a indução da anestesia e de administrar medicamentos para reverter a depressão respiratória como a naloxona, bem como utilizar animais que não apresentem nenhum tipo de comprometimento respiratório. Portanto, a inclusão de analgesia e a oxigenação nos protocolos anestésicos injetáveis devem ser utilizadas de forma rotineira garantindo a mínima presença de dor e, com isso, resultados mais confiáveis nos procedimentos experimentais. / Ensuring the wellbeing of laboratory animals and avoiding unnecessary pain and suffering is one of the main considerations in experimentation. Therefore, the investigation of new anesthetic protocols that guarantee a minimum or null discomfort of the animals has become a priority theme. In this study, it was made an evaluation of the effect of the combination of xylazine (X) and ketamine (K) with acepromazina (A) and opioids [methadone (Me), morphine (Mo) e tramadol (T)] with the purpose of comparing their influence on the physiological parameters of laboratory rats, for both sexes, and evaluating their analgesic power and the effect of the oxygenation on them. The XKA protocol for male and females rats and the XKMe protocol for females were the safest and most effective for anesthetic procedures. However, the results of the formalin test with the measurement of the ultrasonic vocalization (VUS) suggest that the XKA protocol had a low analgesic power, and it is not indicated for procedures that can generate moderate or severe pain. All anesthetic protocols had important effects as diuresis, maintenance of open eyes, and hyperglycemia; these effects should be considered when they could influence in the experimental results. It was demonstrated that oxygenation improves oxygen saturation (SO2) and oxygen partial pressure (pO2) confirming that its use should be considered in the experimental procedures with injectable anesthesia to avoid hypoxemia. Nevertheless, a respiratory acidosis was observed due to the increase in partial pressure of CO2 (pCO2) and the decrease in pH, that could be caused for the hypoventilation due to respiratory depression and CO2 accumulation during the course of anesthesia. This leads to consider the need to pre-oxygenate animals from induction, to use drugs to reverse respiratory depression such as naloxone, and to work with animals that are not respiratory compromised. Therefore the inclusion of analgesia and oxygenation in anesthesia protocols should begin to be used routinely ensuring minimal presence of pain and thus more reliable results in the experimental procedures.

Patients experience some degree of pain accompanying all surgical procedures. If this pain is not adequately treated, it will cause severe physiological and psychological damage. It will even affect patients' postoperative recovery. However, if preemptive analgesia is administered before noxious stimuli arise, rather than afterwards, it is significantly more effective. The purpose of this study is to recognize that reasonable effort and time should be spent to determine a patient's tolerance level towards pain before surgery. Then, the appropriate dosage of analgesia can be given immediately after surgery to alleviate pain. By administering effective pain relief, it will improve patient¡¦s satisfaction with medical services. Using classic experimental design (which consists of an experimental group and a control group), this study focuses on cases of patients who had hemorrhoid surgery in a certain hospital in southern Taiwan. The experimental group and the control group consist of a total of 75 valid samples. The experimental group received customizing analgesic postoperative care, while the control group received conventional analgesic postoperative care. Patient¡¦s satisfaction questionnaires were gathered from patients on the day they were discharged from the hospital. Instruments used in the experiment include VAS, PThM, and patient¡¦s satisfaction questionnaires.To examine the basic characteristics of the samples in both the experimental group and the control group, two statistical methods, Chi-square test and independent T test, were adopted. For patient¡¦s satisfaction questionnaires, Mann-Whitney-Wilcoxon test of nonparametric method was adopted to examine if obvious differences in satisfaction levels existed between the two groups. The result of the experiment shows the analgesic effect from customizing analgesic postoperative care is far better than conventional care. The patient¡¦s satisfaction toward the doctor's professional skill was higher as well. On the other hand, the patient¡¦s satisfaction level toward the whole medical process had no obvious improvement. This study proves that customizing analgesic postoperative care can effectively prevent postoperative pain from occurring. However, to raise patient¡¦s satisfaction towards the whole medical process, better professional medical skill is required as well as improved medical services.

Bakgrund: Receptfria smärtstillande läkemedel (rslm) är lättåtkomliga läkemedel som unga individer kan självmedicinera med. Psykisk ohälsa bland unga ökar, vilket skulle kunna påverka användandet. Skolsköterskor har ofta god insyn i skolelevers livssituation och kan ha en god uppfattning om hur skolelever använder rslm. Syfte: Att undersöka skolsköterskans uppfattning om användandet av rslm bland skolelever i Uppsala kommun samt jämföra uppfattningar mellan skolsköterskor i grundskola och på gymnasiet. Metod: En deskriptiv och komparativ tvärsnittsstudie med kvantitativ ansats. Urvalsgruppen var 62 skolsköterskor i Uppsala kommun. En webbenkät användes för datainsamling och data analyserades i huvudsak med deskriptiv statistik. Resultat: Majoriteten av skolsköterskorna visste inte om eleverna använder rslm på rätt indikation, i rätt dos eller om en ökning skett de senaste tio åren. Majoriteten (59 %) uppfattade att det ofta är samma elever som efterfrågar rslm. Det fanns signifikant skillnad i några uppfattningar mellan skolsköterskorna på grundskolan och gymnasiet men antalet deltagare var lågt, vilket gör resultatet av jämförelse osäkert. Huvudvärk uppfattades som den vanligaste orsaken till efterfrågan av rslm (86,8 %). De vanligaste orsakerna till huvudvärk hos elever uppfattades vara missad måltid (64,9 %) och dålig sömn (64,9 %). De vanligaste orsakerna till generellt magont hos elever uppfattades vara missad måltid (45,9 %) och till nackvärk uppfattades vara användande av mobil, dator och surfplatta (52,9 %). Slutsats: Många skolsköterskor hade ingen uppfattning om elevers användande av rslm. Elever har smärttillstånd som kan bottna i flera orsaker. Fler studier inom det här ämnet behövs för att kunna identifiera hur användandet av rslm ser ut bland unga. / Background: Over-the-counter analgetics are easily accessible and something that young individuals can use for self-medication. Mental health problems increase among young individuals which can affect their use. School-nurses often have a good insight into the lives of school-children, and can therefore identify how school-children use over-the-counter analgetics. Aim: To examine school-nurses perceptions about the use of over-the-counter analgetics among school-children in the community of Uppsala and compare perceptions between school-nurses in elementary schools - and in the high schools. Method: A descriptive and comparative cross-sectional study with a quantitative approach. The sample was 62 school-nurses in the community of Uppsala. Data was collected by an internet-based survey and was mainly analyzed with descriptive statistics. Results: The majority of the school-nurses don’t know if over-the-counter analgetics are used properly, as prescribed, with the correct doses, or if the use has increased over ten years. The majority perceive that it's often the same school-children that request over-the-counter analgetics. There was a significant difference in some perceptions, but due to the low participation, the value of significant data can be vague. Headaches was the most common causes to request over-the-counter analgetics (86,8 %). The perceptions of the most common causes of headaches among school-children were skipping meals (64,9 %), and sleeping problems (64,9 %). The most common causes of general stomach-aches were skipping meals (45,9 %), the most common causes of neck pain were the use of cellphones, computers and tablet devices (52,9 %). The majority of the school-nurses don’t know if over-the-counter analgetics are used properly, as prescribed, with the correct doses, or if the use has increased over ten years. The majority perceive that it's often the same school-children that request over-the-counter analgetics. There was a significant difference in some perceptions, but due to the low participation, the value of significant data can be vague. Conclusion: Many school-nurses are interrogative to questions about school-children’s use of over-the-counter analgetics. School-children have pain conditions for several causes. More studies about this subject are needed to be able to identify the use among school-children.