Bakgrund: Heroin är en opiat ursprungen från opiumvallmon och är starkt förknippad med beroende och död. När heroin och andra kortverkande opiater binder in till μ-opioidreceptorer i hjärnan sker en ökad frisättning av signalsubstansen dopamin och en stark känsla av eufori infinner sig. Vid upprepat intag sker förändringar i hjärnan; belöningseffekten minskar medan antibelöningseffekterna ökar och cravings och abstinensymptom blir allt tydligare vid frånvaro av drogen. Vid läkemedelsassisterad rehabilitering vid opiatberoende (LARO) används förutom psykosocial behandling även långverkande opioider såsom opioidagonisten metadon och den partiella opioidagonisten buprenorfin, för att återställa homeostasen och reducera cravings och abstinenssymptom som opioidberoendet har skapat. Metadon är effektivt vid beroendebehandling men dess risker begränsar dess användning. Buprenorfin har lägre överdospotential men eventuellt sämre effekt än metadon. Syfte: Syftet med denna litteraturstudie var att undersöka skillnad i effekt mellan buprenorfinpreparat och metadon vid behandling av opioidberoende. Metod: Arbetet är en litteraturstudie baserat på fem vetenskapliga studier vilka har erhållits via sökning i PubMed samt Cochrane Library. De aspekter som avhandlats är; fullföljande och retention av behandling, samtidigt sidomissbruk av opiater samt allvarliga incidenter och biverkningar. Resultat: De inkluderade studierna i denna litteraturstudie visade att metadon är bättre på att bevara patienter i behandling medan buprenorfin mer effektivt kan minska sidomissbruket av opiater. Ju högre doser som användes, desto fler deltagare stannade kvar i behandling och desto färre urinprover rapporterades positiva för sidomissbruk av opiater. Få allvarliga incidenter rapporterades från studierna. Slutsats: Både metadon och buprenorfinpreparaten har sina för- och nackdelar.  Då behandling med metadon tidigare bevisats vara mer riskfyllt bör buprenorfinpreparaten utgöra förstahandsval, men vid otillräcklig effekt bör byte till metadon ske. Detta överrensstämmer med riktlinjerna i Sverige idag. Dock tycks det finnas anledning att i framtida studier undersöka dos-effekt-samband för både dessa preparat, samt också att fokusera på den initiala fasen vid behandling med buprenorfin. / Background: Heroin is an opiate from the opium poppy which is strongly associated with dependence, overdose and death. When heroin and other opiates binds to the μ-opioid receptors located in the brain, dopamine is released from the ventral tegmental area and a strong feeling of euphoria arises. Continuous intake of opioids cause changes in the brain and the feeling of euphoria will be less distinct during drug intake. Instead, cravings and abstinence, will be more distinctive in absence of the drug and causes drug-abusers to continue to use the drug. The cravings and abstinence is due to an overactive HPA-axis and amygdala. This overactivity can be reduced by treatment with long lasting opioids that is used in treatment of opioid dependence. The development of opioid maintenance treatment started in the US during the early 1960s. A few years later, opioid dependent people could join the first opioid maintenance treatment program in Uppsala, Sweden. The opioid maintenance treatment involves both pharmacological and psychosocial treatment. There are two main substances available for opioid maintenance treatment in Sweden: methadone, a full μ-opioid receptor agonist and buprenorphine, a partial μ-opioid receptor agonist. Methadone has been proven to be very efficacious treating opioid dependence. However, the risk of overdose leading to respiratory depression, limits its usefulness. Buprenorphine on the other hand, has a lower risk of toxicity but may not have same efficacy as methadone. Aim: The purpose of this literature study is to examine the efficacy of buprenorphine versus methadone among patients in opioid maintenance treatment. Methods: Five different randomized, controlled trials were selected from PubMed and The Cochrane Library to be included in this literature study. To limit this degree project, four variables was selected: completion and retention in treatment, use of illicit opiates during treatment and adverse events associated with treatment medication. Results: According to the findings in the five studies, methadone can be considered as a better option than buprenorphine when it comes to retaining participants in treatment. However, buprenorphine is somewhat more effective reducing the illicit use of opiates. When both methadone and buprenorphine were used in higher doses, more participants stayed in treatment. Also, higher doses were associated with a lower portion of urine samples positive for illicit opiates. Few adverse events were documented from the studies. Conclusion: Both methadone and buprenorphine have advantages and disadvantages. Since treatment with methadone is more perilous, buprenorphine should be considered as first-line treatment. But if the clinical effect remains insufficient, a transition to methadone treatment should occur, all according to the guidelines of opioid maintenance treatment in Sweden. However, future studies should consider evaluating the relationship between dose and effect of buprenorphine and possibly also methadone. Furthermore, more focus should be added on the initiation phase of treatment with buprenorphine.

Made available in DSpace on 2014-06-11T19:31:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-12-17Bitstream added on 2014-06-13T19:20:10Z : No. of bitstreams: 1 pereira_da_dr_jabo.pdf: 1782082 bytes, checksum: 77e52685e1f96a8aa8b16c4ad7bfc7f8 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A metadona é um opioide pouco utilizado na prática veterinária, sendo que existem ainda, questionamentos quanto ao seu uso. Dessa maneira, objetivou-se comparar o emprego da metadona, administrada por via intramuscular e intravenosa e seus efeitos sobre os parâmetros cardiorrespiratórios e profundidade anestésica em cadelas submetidas à ovariossalpingohisterectomia. Utilizaram-se 16 cadelas (103 kg), pré-medicadas com levomepromazina (0,5 mg/kg, IM). Transcorridos 20 minutos, a indução anestésica foi realizada com propofol (5 mg/kg, IV) e a manutenção com isofluorano. Após 10 minutos, os animais receberam metadona pelas vias IM (GIM) e IV (GIV), na dose de 0,3 mg/kg, diluídos em solução fisiológica (volume total=1ml/5kg). As mensurações das variáveis frequências cardíaca (FC) e respiratória (f), pressões arteriais (PAS, PAD e PAM), eletrocardiografia (ECG), temperatura esofágica (TE), pressão parcial de dióxido de carbono no final da expiração (EtCO2), saturação da oxihemoglobina (SpO2) e índice biespectral (BIS) iniciaram-se antes da administração do opioide (M0), 20 minutos após M0 (M1) e a cada 10 minutos (M2 a M5). As mensurações do cortisol foram obtidas em M0 (antes do opioide), M2, M5 (30, 60 minutos após a metadona), M6, M7 e M8 (1, 3 e 6 horas após OSH). A análise estatística utilizada foi a de Perfil, testes t, de Tuckey, e Kruskal-Wallis (5%). Foram observados tempos de extubação e recuperação maiores no GIV. Com relação à f, FC, PAM, TE, EtCO2, SpO2 e BIS não foram observadas diferenças significativas entre grupos e momentos. Não foi observada diferença entre grupos para os níveis de cortisol. Entre momentos, no GIM, as concentrações de cortisol em M0 foram menores do que em M7. Para a escala descritiva (escores) não foram observadas diferenças entre grupos e momentos / Methadone is an opioid little used in veterinary practice, and there are still questions about its use.Thus, the aim of this study was to compare the effects of intramuscular (IMG) and intravenous (IVG) administration of methadone on cardiopulmonary parameters, biespectral index and analgesic requirements in female dogs submitted to ovariohysterectomy. Sixteen female dogs were used (10±3 kg), premedicated with levomepromazine (0,5 mg/kg, IM). After 20 minutes, propofol (5 mg/kg) was used for induction and the anesthesia was maintained with isoflurane. After 10 minutes, methadone at 0.3 mg/kg was administered intravenously in IVG and intramuscularly in IMG, diluted in physiological saline (total volume of 1ml/5kg). The initial measurement of heart ( HR) and respiratory rates (RR), arterial pressures (SAP, DAP and MAP), electrocardiogram (ECG), body temperature (BT), concentration of end-tidal carbon dioxide (PECO2), peripheral oxygen saturation (SpO2) and biespectral index (BIS) was performed immediately before the administration of opioid (M0), after 20 minutes (M1) and then at 10-minute intervals (M2, M3, M4 and M5). Serum cortisol concentrations (Sc) were measured at M0, M2, M5 (30 and 60 minutes after opioid, and 1(M6), 3 (M7) and 6 (M8) hours after the end of surgery. The statistical analysis used was profile and tests “t”, Tuckey and Kruskal-Wallis (5%). Times of extubation and recovery were higher in IVG. HR, RR, APM, BT, PECO2, SpO2 and BIS did not differ significantly among times or between groups at any time. No differences were observed between groups for Sc. Between moments, in IMG, Sc at M0 were lower than at M7. For the descriptive scale (scores), no differences between groups or among times were observed

Made available in DSpace on 2016-12-08T16:24:14Z (GMT). No. of bitstreams: 1 PGCA13MA104.pdf: 1965004 bytes, checksum: abf177b639035d63846aaabc8ace39dc (MD5) Previous issue date: 2013-02-15 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The prevention and control of pain are basic components to have an adequate anesthesia. In this sense objective with this study, to investigate the postoperative analgesia of ketamine in subanestésica dose of methadone and the association of both intramuscularly in cats. A total of 24 cats, mongrel, weighing on average 2.8 ± 0.6 kg, proven healthy by clinical examination and laboratory referred for elective ovariossalpingohisterectomia. The day before the beginning of the experiment, animals were anesthetized with propofol for placing a catheter in the jugular vein for subsequent blood sampling for measurement of cortisol. The next day, animals were randomly allocated to three groups, which received ketamine group (n = 8) the dose of 0.5 mg / kg; methadone (GM, n = 8) the dose of 0.3 mg / kg; methadone and ketamine (GCM, n = 8) at doses of 0.5 mg / kg and 0.3 mg / kg, respectively, all the intramuscular route. All groups received the drug 20 minutes before surgery, and then were induced with propofol dose effect and maintained with isoflurane in system without rebreathing, diluted in 100% oxygen, and the surgical procedure performed by the same surgeon . The postoperative evaluation consisted of measurement of cortisol and pain scores using the multidimensional acute pain in cats, which assesses psychomotor change, including posture, comfort, activity and attitude; protecting the painful area by the reaction to palpation surgical wound reaction to palpation of the abdomen / flank; physiological variables, the measurement of systolic blood pressure and appetite, and vocal expression of pain. The collection of samples for cortisol measurement was performed one hour before surgery, during surgery (between clamping pedicles) and postoperative (1, 2, 3, 4, 8, 12 and 24 hours) and evaluation pain hour before surgery and at times 1, 2, 3, 4, 8, 12 and 24 hours after surgery. The cortisol levels were higher in CG compared to GM and GCM in M2, M3 and M4. Pain scores were higher in GC in moments M2, M3 and M4 compared to GM and GCM, respectively. In summation of points in M2 and M3, CG showed higher values than GM and GCM, and M5, CG obtained values greater than GCM. Only variables PAS and voicing the pain did not differ significantly between groups and between moments. Regarding the number of redemptions postoperatively in GC 100% (8/8) of animals requiring rescue, GM at 62.5% (5/8) and GCM 37.5% (3/8). It was concluded that intramuscular administration of the combination of ketamine and methadone reduces the analgesic application postoperatively. The analgesia provided by ketamine alone was unsatisfactory due to the high need for rescue analgesic / A prevenção e o controle da dor são componentes básicos para se ter um procedimento anestésico adequado. Neste sentido objetivou-se com este estudo, investigar a analgesia pósoperatória da cetamina em dose subanestésica, da metadona e a associação de ambas pela via intramuscular em felinos. Foram utilizadas 24 gatas, sem raça definida, pesando em média 2,8 ± 0,6 kg, comprovadamente hígidas através de exame clínico e laboratorial, encaminhadas para ovariossalpingohisterectomia eletiva. No dia anterior ao início do experimento, os animais foram anestesiados com propofol para colocação de cateter na veia jugular, para posterior coleta de sangue para mensuração do cortisol. No dia seguinte, os animais foram alocados aleatoriamente em três grupos, os quais receberam cetamina (GC, n=8) na dose de 0,5mg/Kg; metadona (GM, n=8) na dose de 0,3mg/Kg; e cetamina e metadona (GCM, n=8) nas doses de 0,5mg/Kg e 0,3mg/Kg, respectivamente, todos pela via intramuscular. Todos os grupos receberam os fármacos 20 minutos antes do procedimento cirúrgico, e em seguida foram induzidos com propofol a dose efeito e mantidos com isofluorano em sistema sem reinalação de gases, diluído em oxigênio a 100%, sendo o procedimento cirúrgico realizado sempre pelo mesmo cirurgião. A avaliação pós-operatória constou de mensuração do cortisol e escore de dor através da escala multidimensional de dor aguda em felinos, a qual avalia alteração psicomotora, incluindo postura, conforto, atividade e atitude; proteção da área dolorosa, através da reação à palpação da ferida cirúrgica, reação à palpação do abdome/flanco; variáveis fisiológicas, pela aferição da pressão arterial sistólica e apetite; e expressão vocal da dor. A coleta de amostra para mensuração do cortisol foi realizada uma hora antes do procedimento cirúrgico, no trans-operatório (entre pinçamento de pedículos) e no pós-operatório (1, 2, 3, 4, 8, 12 e 24 horas) e a avaliação de dor uma hora antes do procedimento cirúrgico e nos momentos 1, 2, 3, 4, 8, 12 e 24 horas após a cirurgia. Os valores de cortisol foram maiores no GC em comparação ao GM e GCM em M2, M3 e M4. Os escores de dor foram maiores no GC nos momentos M2, M3 e M4 em comparação ao GM e GCM, respectivamente. No somatório de pontos, em M2 e M3, GC apresentou valores maiores que GM e GCM, e em M5, GC obteve valores maiores que GCM. Apenas as variáveis PAS e vocalização à dor não apresentaram diferença significativa entre grupos e entre momentos. Em relação ao número de resgates no pós-operatório no GC 100% (8/8) dos animais necessitaram de resgate, no GM 62,5% (5/8) e no GCM 37,5% (3/8). Conclui-se que a administração intramuscular da associação de cetamina e metadona reduz o requerimento analgésico no pós-operatório. A analgesia promovida pela cetamina isolada foi insatisfatória devido a alta necessidade de resgate analgésico

A dor aguda pós-operatória tem suscitado grande interesse por seu potencial risco de cronicidade caso não seja adequadamente tratada, podendo piorar a recuperação e a qualidade de vida do paciente. Este estudo comparativo foi realizado de maneira prospectiva, aleatória e encoberta para se avaliar os efeitos sedativos, analgésicos e na resposta inflamatória da administração de metadona ou tramadol. Foram incluídos 28 cães com ruptura de ligamento cruzado e submetidos a osteotomias corretivas, distribuídos em três grupos: TRA - 4 mg/kg de tramadol; MET0,5 - 0,5 mg/kg de metadona e MET0,7 - 0,7 mg/kg de metadona, administrados por via intramuscular na medicação pré-anestésica (MPA). A indução da anestesia foi realizada com propofol e os animais foram intubados e mantidos com isofluorano em oxigênio a 100%. Parâmetros fisiológicos (frequências cardíaca, respiratória e pressão arterial) foram avaliados nos dados momentos: TBL (basal), T1 (uma hora após a MPA), T2 (duas horas após, transcirúrgico), T4 (quatro horas após, pós-cirúrgico), T6 (seis horas após) e T24 (24 horas após). Escores de sedação e dor foram avaliados por escalas em TBL, T1, T4, T6 e T24. Coletas de sangue para mensuração de IL-6 foram realizadas em TBL, T1, T6 e T24. Animais apresentando escores na escala análoga visual maiores que 4, na escala de Glasgow maiores que 5 ou na escala de Colorado maiores que 2, recebiam analgesia complementar com o fármaco do grupo em que foram alocados. Utilizou-se análise de variância para medidas repetidas (ANOVA) com pós teste de Tukey para análise estatística dos parâmetros fisiológicos. Escores de dor e sedação foram comparados entre diferentes momentos por teste de Friedman, seguido de teste de Tukey. Os grupos foram comparados em um mesmo momento, por teste não-paramétrico Kruskal-Wallis, seguido de teste post hoc de Dunn. Valores de p<0,05 expressam diferença significativa. Não houve diferença entre os grupos com relação a idade, peso e sexo, além de tempos de cirurgia e extubação. Os valores de frequência cardíaca, respiratória e pressão arterial mantiveram-se dentro dos parâmetros aceitáveis nas condições avaliadas, havendo redução nos valores em T2 nos grupos MET0,5 e MET 0,7 com relação ao TBL. Para os escores na escala análoga visual, dentro do grupo TRA houve aumento significativo em T4 comparado a TBL, T1 e T24 e entre T1 e T6 (p<0,001). No grupo MET0,5, houve aumento significativo de T1 para T4 (p<0,001). Os grupos TRA e MET0,5 apresentaram médias±DP mais altas (3,4±2,5 e 2,5±2,6, respectivamente) que MET0,7 (1,1±1,5) em T4. Na escala de dor de Glasgow, em MET0,5, houve aumento significativo no momento T4 com relação aos momentos T6 e T24 (p<0,001). No grupo MET0,7, houve aumento significativo no momento T4 para TBL e T24 (p<0,001). Houve maior necessidade de resgate no grupo TRA (quatro animais em T4 e dois em T6), contudo após um incremento na dose do fármaco, obteve-se controle adequado da dor. Não foram observadas diferenças estatísticas significativas quanto ao grau de sedação, escala de Colorado e interleucinas séricas entre os grupos e momentos avaliados. A metadona e o tramadol foram eficazes em promover analgesia pós-operatória quando administrados antes do procedimento cirúrgico e suas doses ajustadas no resgate analgésico. Ambos parecem ter tido efeito sobre a liberação de IL-6, sugerindo modulação da resposta inflamatória aguda / Acute postoperative pain has aroused great interest because of their potential risk of chronification if not treated properly, may worsen the recovery and quality of life of the patient. This clinical trial was conducted in a prospective, randomized, double-blind comparison to evaluate the efficacy of methadone and tramadol as premedication in dogs. 28 animals with ruptured cruciate ligament undergoing corrective osteotomies were divided into three groups: TRA - received 4 mg/kg of tramadol; MET0.5 - received 0.5 mg/kg of methadone and MET0.7 - received 0.7 mg/kg of methadone intramuscularly. Anesthesia induction was performed with propofol and animals intubated for general anesthesia with isoflurane in 100% oxygen. Physiological parameters (heart and respiratory rate and blood pressure) were evaluated at specified times (in hours): TBL (baseline), T1, T2, T4, T6 and T24. Pain and sedation scores were described by use of visual analogue scale (VAS), composite modified Glasgow scale and Colorado scale at TBL, T1, T4, T6 and T24. Blood samples for measurement of IL-6 were performed in moments TBL, T1, T6 and T24. Statistical analysis was performed by ANOVA for repeated measurements. Pain and sedation scores were compared in different times by Friedman\'s test followed by Tukey test. Groups were compared by non-parametric Kruskal-Wallis test followed by post hoc Dunn\'s test. Values with p <0.05 were considered significant. There was no statistically significant difference among groups with respect to age, weight, gender, time of surgery and time for extubation. Heart rate, respiratory rate and blood pressure values were maintained within acceptable values and a reduction was observed in T2 in groups MET0.5 and MET0.7 in relation to TBL. Increases in VAS scores were observed in TRA in T4 compared to TBL, T1 and T24 and between T1 and T6 (p<0.001). In MET0.5 there was a significant increase in T4 when compared to T1 (p<0.001). Groups TRA and MET0.5 showed higher mean±SD values (3.4±2.5 and 2.5±2.6, respectively) than MET0.7 (1.1±1.5) in T4. In Glasgow pains scale, there was significant increase in T4 when compared to T6 and T24 (p<0.001). In MET0.7, T4 showed higher scores than TBL and T24 (p<0.001). TRA showed greater demand of rescue analgesia (four animals in T4 and two in T6), however after a dose adjustment pain was controlled. There were no statistically significant differences in degree of sedation, Colorado acute pain scale and serum interleukin among groups and time points assessed. Both drugs were effective in promoting postoperative analgesia when administered prior to surgical procedure and the doses adjusted according to demand. The drugs appear to have an effect on the release of IL-6, suggesting acute inflammatory response modulation

The objective of this study was to evaluate the cardiovascular effects and compare the analgesic efficacy intraoperative and postoperative provided by methadone administered via epidural (EP) or intramuscular (IM) in bitches submitted to total unilateral mastectomy surgery. For this it was used 12 female dogs anesthetized and randomly distributed into two groups of six animals each. In the first group the methadone was administered via epidural, after anesthetic stabilization (GEP) and another group, methadone was administered via intramuscular in the pre-anesthetic medication (GIM). In the first part of the study evaluated heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), mean arterial pressure (MAP), diastolic blood pressure (DBP), carbon dioxide released at the end of expiration (ETCO 2) and arterial blood gas analysis. Both FC when FR and blood gas analysis did not show significant changes. The GIM had higher values in all pressure ratings (DAP, MAP and SAP), but within the parameters for the species. The GIM had higher values in all pressure ratings (DAP, MAP and SAP), but within the range for the species. Both routes of administration showed little change in the evaluated parameters, however the epidural demonstrated greater anesthetic and analgesic stability for this procedure. In the second part of the study, the postoperative analgesia was measured by pain scales at the University of Melbourn, Visual Analogue Scale (VAS) and Glasgow Simplified Composed Measure pain scale. It also evaluated serum concentration of cortisol, lactate and glucose. Difference was observed between the groups only in the T6 Melbourn scale and analgesic rescue at T2 to the animals of the GIM. Cortisol presented a significant enhancement in the first hour in both groups and the remaining analyzes did not demonstrate differences. The administration of methadone epidural provided higher postoperative analgesia period that intramuscular administration showing to be the best option for this procedure. For both steps, the mean scores were submitted to statistical analysis by Kruskal-Wallis test to the groups between the different moments and Wilcoxon to compare the groups within each time. The Scott-Knott post-test was used for comparison in pairs at 5% significance level. After observing of the study in its two steps can be concluded that both methadone administered via epidural as intramuscular are secure in the perioperative period because does not cause significant changes in the physiological parameters. However the epidural proved to have a more efficient analgesia during surgery and post-operative period, in which we observed a greater analgesia period which makes it a safe and the best route for satisfactory analgesia in the procedure and in the studied species. / O objetivo do presente estudo foi avaliar os efeitos cardiovasculares e comparar a eficácia analgésica transoperatória e pós-operatória proporcionada pela metadona administrada pela via epidural (EP) ou pela via intramuscular (IM) em cadelas submetidas à cirurgia de mastectomia unilateral total. Para tanto foram utilizadas 12 cadelas anestesiadas e distribuídas aleatoriamente em dois grupos compostos de seis animais cada. Em um grupo foi administrado metadona via epidural após estabilização anestésica (GEP) e em outro grupo a metadona foi administrada via intramuscular na medicação pré-anestésica (GIM). Na primeira parte do estudo foram avaliados frequência cardíaca (FC), frequência respiratória (f), pressão arterial sistólica (PAS), pressão arterial média (PAM), pressão arterial diastólica (PAD), tensão de dióxido de carbono ao final da expiração (ETCO2) e hemogasometria do sangue arterial. Tanto a FC, quanto f e hemogasometria não apresentaram alterações significativas. O GIM apresentou valores mais altos em todas as avaliações das pressões (PAD, PAM e PAS), porém dentro dos parâmetros para a espécie. As duas vias de administração demonstraram poucas alterações nos parâmetros avaliados, entretanto a via epidural demonstrou maior estabilidade anestésica e analgésica para esse procedimento. Na segunda parte do estudo, a analgesia pós-operatória foi avaliada pelas escalas de dor da Universidade de Melbourn, Escala Visual Analógica (EVA) e escala de dor de Medida Composta de Glasgow Simplificada. Avaliou-se também concentração sérica de cortisol, lactato sérico e glicemia. Foi observada diferença entre os grupos somente no T6 pela escala de Melbourn, e resgate analgésico no T2 para os animais do GIM. O Cortisol apresentou aumento significativo na primeira hora de avaliação em ambos os grupos e as demais análises não demonstraram diferenças. A administração de metadona via epidural proporcionou maior período de analgesia pós-operatória que a administração intramuscular sendo a melhor opção para esse procedimento. Para ambas as etapas as médias dos escores foram submetidas a análise estatística pelos testes Kruskall-Wallis para os grupos entre os diferentes momentos e Wilcoxon para comparar os grupos dentro de cada tempo. O pós-teste de Scott-Knott foi utilizado para comparação aos pares ao nível de 5% de significância. Após a observação do estudo em suas duas etapas pode-se concluir que tanto a metadona administrada pela via epidural quanto a via intramuscular são seguras no período transoperatório por não causar alterações significativas nos parâmetros fisiológicos estudados, entretanto a via epidural se mostrou mais eficiente em relação a analgesia tanto nesse período quanto no período pós-operatório, onde foi possível observar um maior período analgésico, tornando-a uma via segura para no procedimento e espécie estudados.

L’objectif de cette thèse a été d’explorer l’association entre des variants génétiques impliqués dans la variabilité interindividuelle de la réponse au traitement par les opioïdes et la survenue d’effets secondaires. Nous avons recherché si des facteurs génétiques influençaient la réponse à la morphine dans le traitement de la douleur aigüe. L’allèle T du polymorphisme c.3435C>T d’ABCB1 est significativement associé aux doses de morphine et à la survenue de nausées dans une étude pilote chez des patients libanais en post-opératoire. Ensuite, l’étude de la réponse à la morphine chez des patients présentant une obésité morbide a montré que la fréquence de l’allèle 118G d’OPRM1 et le seuil de sensibilité à la douleur sont plus élevés que chez les patients à poids normal. La recherche des facteurs influençant la variabilité de la réponse à la méthadone chez des patients toxicomanes traités pour substitution a mis en évidence deux polymorphismes (TaqIA de DRD2/ANKK1 et c.118A>G d’OPRM1) significativement associés à la dose maximale de méthadone administrée. Trois facteurs sont associés au phénotype CYP3A, impliqué dans le métabolisme de la méthadone: la prise de benzodiazépines, l’infection par le VIH et un polymorphisme de POR, gène qui code une oxydoréductase. De plus, le travail mené sur les effets secondaires cardiaques de la méthadone a permis de mettre en évidence trois facteurs corrélés à l’allongement de l’espace QT : la dose, l’infection par le VIH et le polymorphisme p.Lys897Thr de KCNH2 codant pour le canal potassique hERG. Ces travaux contribuent à démontrer l’intérêt d’intégrer des données cliniques et génétiques dans la prescription personnalisée des opioïdes. / The main objective of this thesis was to explore the association between genetic variants potentially involved in inter-individual variability of opioids’ response and side effects in the treatment of pain and opiate substitution treatment. Initially, we investigated whether genetic factors influence the response to morphine in the treatment of acute pain. The T allele of the polymorphism ABCB1 c.3435C>T was significantly associated with doses of morphine and the outcome of nausea in a pilot study in Lebanese postoperative patients. Next, we examined the response to morphine in patients with morbid obesity (BMI>40); in these patients, the frequency of the 118G OPRM1 allele and the pain threshold appeared to be higher than in patients with normal BMI. The search for factors influencing the variability in response to methadone in patients treated for drug substitution showed that two polymorphisms (DRD2/ANKK1 TaqIA and OPRM1 c.118A>G) were significantly associated with the maximum doses of methadone. In addition, three factors were associated with the CYP3A phenotype, involved in the metabolism of methadone: the use of benzodiazepines, HIV infection and a polymorphism in POR gene, which encodes an oxidoreductase. Finally, the exploration of the cardiac side effects of methadone has highlighted three factors significantly correlated with QT prolongation: methadone doses, HIV infection and the polymorphism p.Lys897Thr in KCNH2 encoding a cardiac potassium ion channel. This work demonstrates the importance of integrating both clinical and genetic data in the personalized prescription of opioids.

Made available in DSpace on 2016-01-26T18:55:27Z (GMT). No. of bitstreams: 1 Dissertacao Camila.pdf: 356742 bytes, checksum: d31eb9f6798556536fdad46d8eb56d72 (MD5) Previous issue date: 2008-08-27 / This study compared the analgesic, sedative and neuroendocrine effects of the epidural (EP) and intramuscular (IM) methadone in cats submitted to ovariohisterectomy. Cats were randomly assigned to three groups of 08 animals each and received EP or IM methadone (0.2mg.kg-1 diluted with saline to 0.2ml.kg-1, G1 and G2, respectively) or a saline placebo (G3). Pre-anaesthetic medication was acepromazine (0.1mg.kg-1 IM). Anaesthesia was induced with thiopental (12mg.kg-1 IV) and maintained with halothane. Serum cortisol concentration, behavioral changes, degree of analgesia and sedation were evaluated. In the epidural methadone group (G1) lower scores of pain were observed when compared with the others groups, but the difference did not significance. Rescue analgesia was administered 3 times to 02 cats in the G1, 9 times to 05 cats in the G2 and 11 times to 06 cats in the G3. It was concluded that the methadone preemptive administration reduced postoperative analgesic requirement. Stress response was modulated by methadone in cats submitted to ovariohisterectomy. / Esse estudo comparou os efeitos analgésicos, sedativos e neuroendócrinos do opióide metadona administrado via intramuscular ou epidural em gatas, submetidas a ovariossalpingohisterectomia (OSH). Os animais foram distribuídos aleatoriamente em três grupos de 08 animais cada, sendo tratados com metadona pela via epidural ou intramuscular (0,2mg.kg-1 diluída em solução salina em volume final de 0.2ml.kg-1, G1 e G2, respectivamente) ou com solução salina (G3) (n=8). Na medicação pré-anestésica foi administrada acepromazina (0,1mg.kg-1 IM), a indução anestésica foi realizada com tiopental sódico (12mg.kg-1 IV), com posterior manutenção em anestesia geral inalatória, com halotano. Avaliaram-se comportamento, grau de analgesia, sedação e concentração sérica de cortisol. No grupo tratado com metadona epidural (G1), foram observados escores inferiores de dor, quando comparados aos demais grupos. Analgesia resgate foi administrada 3 vezes em 2 animais do G1, 9 vezes em 5 animais do G2 e 11 vezes em 6 animais do G3. Conclui-se que a administração preemptiva da metadona reduziu o requerimento de analgésico pós-operatório. Paralelamente, a metadona favoreceu a modulação da resposta de estresse em gatas submetidas à OSH.

Made available in DSpace on 2016-07-18T17:53:05Z (GMT). No. of bitstreams: 1 Dissertacao Camila.pdf: 356742 bytes, checksum: d31eb9f6798556536fdad46d8eb56d72 (MD5) Previous issue date: 2008-08-27 / This study compared the analgesic, sedative and neuroendocrine effects of the epidural (EP) and intramuscular (IM) methadone in cats submitted to ovariohisterectomy. Cats were randomly assigned to three groups of 08 animals each and received EP or IM methadone (0.2mg.kg-1 diluted with saline to 0.2ml.kg-1, G1 and G2, respectively) or a saline placebo (G3). Pre-anaesthetic medication was acepromazine (0.1mg.kg-1 IM). Anaesthesia was induced with thiopental (12mg.kg-1 IV) and maintained with halothane. Serum cortisol concentration, behavioral changes, degree of analgesia and sedation were evaluated. In the epidural methadone group (G1) lower scores of pain were observed when compared with the others groups, but the difference did not significance. Rescue analgesia was administered 3 times to 02 cats in the G1, 9 times to 05 cats in the G2 and 11 times to 06 cats in the G3. It was concluded that the methadone preemptive administration reduced postoperative analgesic requirement. Stress response was modulated by methadone in cats submitted to ovariohisterectomy. / Esse estudo comparou os efeitos analgésicos, sedativos e neuroendócrinos do opióide metadona administrado via intramuscular ou epidural em gatas, submetidas a ovariossalpingohisterectomia (OSH). Os animais foram distribuídos aleatoriamente em três grupos de 08 animais cada, sendo tratados com metadona pela via epidural ou intramuscular (0,2mg.kg-1 diluída em solução salina em volume final de 0.2ml.kg-1, G1 e G2, respectivamente) ou com solução salina (G3) (n=8). Na medicação pré-anestésica foi administrada acepromazina (0,1mg.kg-1 IM), a indução anestésica foi realizada com tiopental sódico (12mg.kg-1 IV), com posterior manutenção em anestesia geral inalatória, com halotano. Avaliaram-se comportamento, grau de analgesia, sedação e concentração sérica de cortisol. No grupo tratado com metadona epidural (G1), foram observados escores inferiores de dor, quando comparados aos demais grupos. Analgesia resgate foi administrada 3 vezes em 2 animais do G1, 9 vezes em 5 animais do G2 e 11 vezes em 6 animais do G3. Conclui-se que a administração preemptiva da metadona reduziu o requerimento de analgésico pós-operatório. Paralelamente, a metadona favoreceu a modulação da resposta de estresse em gatas submetidas à OSH.

Opioids are considered as a dangerous addictive substances which are widely used in medicine for their strong analgetic effects. Opioids (such as morphine and methadon) may nevertheless play an important role in the resistance of the heart to ischemia by reducing the rate of cell damage. This protective effect is well understood about morphine but we don't know almost nothing about effects of methadone on the myocardium. The main aim of this thesis was to find out how chronic methadone treatment affects ischemic tolerance of rat hearts. For our experiments we used Wistar rats in two series. In the first series we administered morphine (10 mg/kg/day, i.m.) or methadone (2 mg/kg/day, i.m.) for 10 days. In the second experiment series we administered methadon for 28 days (2 mg/kg/day, i.m.). For analysis of the ischemic heart tolerance we used the isolated perfused heart method. Incidence and severity of ischemia and reperfusion arrhythmias were analyzed during the 50 min of ischemia and early reperfusion. Infarct size was analyzed histochemically, using tetrazolium salts and KMnO4 1 h after reperfusion and was determined by planimetric method. In the first series of experiments analyzing the effect of 10-day administration of both opioids on the resistance of the heart to ischemia we did not find a...

Opioid abuse costs affect the majority of the adult population in our society directly or indirectly. The current prevailing medical treatment for opioid addiction is methadone maintenance treatment (MMT). MMT reduces infectious disease spread, illicit drug use, criminal activity, and overdose potential. MMT is only as effective as the length of time a client remains active and compliant with the program. In previous studies, therapeutic alliance (TA) has been shown to positively influence the effectiveness of substance abuse treatment. However, a gap exists in research in regards to the impact of TA on the effectiveness of MMT outcomes. The theoretical framework of this study is based on therapeutic alliance, which guided an examination on whether therapeutic alliance (as measured by the Session Rating Scale) influenced MMT retention and compliance (drug screens and session attendance). Archival data from 264 clients receiving MMT for opioid dependence were reviewed from a nonprofit community-based agency in Arizona. Logistic regression results revealed that TA did not significantly affect retention or compliance. However, issues were noted such as how the SRS was administered, a lack of understanding by clients regarding scoring the SRS, and unique social desirability demands when clients are in MMT. The finding that TA alone did not significantly affect retention and compliance does not decrease the need to find effective means to improve MMT outcomes. Rather, the findings suggest a critical need to identify and utilize measures more appropriate for clients receiving MMT. In doing so, positive social change may be achieved by assisting clinical staff in developing a strong therapeutic alliance with MMT clients as they focus on problem solving as a joint venture when challenges in the recovery process arise.