Made available in DSpace on 2016-04-28T20:18:32Z (GMT). No. of bitstreams: 1 2009 - Priscila Andrade Pires.pdf: 1237061 bytes, checksum: 6489ca08dab0e701c25ed611f45a365e (MD5) Previous issue date: 2009-08-28 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Nonsteroidal anti-inflammatory drugs (NSAID) are widely using in veterinary medicine, having analgesic and anti-inflammatory activity, including reduction of oedema and antipyretic actions. They inhibit the cyclooxygenase enzime (COX). There are two isoforms of COX that are responsible for synthesis of prostaglandins. The COX I is usually a constitutive enzyme expressed in tissues. Prostaglandins, prostacyclin, and thromboxane synthesized by this enzyme are responsible for normal physiologic functions. COX II, on the other hand, is inducible and synthesized by inflammatory cells after stimulation by cytokines and other mediators of inflammation. In some tissues COX II may be constitutive as central nervous system and kidney. All NSAID can cause adverse side effects and their selective degree will be important for the ocurrence of undesirable reaction. The aim of this study was to evaluate the analgesic, antioedematogenic and antipyretic activity of some antiinflammatory used in veterinary clinics, the nonselective drugs, flunixin meglumine (FM) and ketoprofen (CT); the COX II preferential, meloxicam (MX) and carprofen (CP); and COX II selective, firocoxib, after oral administration, as well as their ulcerogenic activity in gastric mucosa, allowing a comparative analyses of their antinociceptive and/or anti-inflammatory actions and their adverse side effects, helping veterinary doctor in the choose of the drug that have better relation cost/risk/benefit of this drugs. To assess the antioedematogenic effect in croton oil-induced mice ear oedema method, the CT (ID50: 3,6 mg/kg) was the most potent drug, followed by CP and FM (ID50: 12,3 and 17,8 mg/kg, respectively). The MX and FC, despite of their effectiveness, showed low activity, didn t producing sufficient effects for determination the ID50 in maximal dose (30 mg/kg). In LPS induced fever in rats, the FC produced antipyretic activity with ID50 2,9 mg/kg, accompanied by CT, CP and FM (ID 50: 3,3; 3,6 and 4 mg/kg, respectively) and with greater dose of meloxicam (ID 50: 30 mg/kg). Evaluating the antinociceptive effect in the acetic acid-induced abdominal writhing model of analgesia in mice, the MX was the most effective drug (ID50: 0,09 mg/kg), followed by FM, FC, CP and CT (ID50: 0,4; 1,9; 2,3; 3,6, respectively), and using this ID50 in the evaluation of ulcerogenic action of this drugs in mice, the FC, FM and MX didn t induce significative gastric injury in 3o and 7o day of treatment. The CT and CP induced ulceration in 3o day, being the CT most intense. However in 7o day, we didn t notice gastric injury, suggesting that adapted gastric mucosa produces increased resistance to subsequent damage by this class of drugs. This results reveal that analgesic activity of almost all of this NSAID is independent of this antiodematogenic and antipyretic actions. The CT has similar ID50 in all pharmacological assays in this study. The gastric ulcerogenic activity has inverse ratio when compared with analgesic effects. / Os anti-inflamat?rios n?o esteroidais (AINES) s?o drogas amplamente usadas na medicina veterin?ria, tendo a??o analg?sica, anti-inflamat?ria, incluindo a redu??o do edema e antipir?tica. Agem inibindo a enzima cicloxigenase (COX), n?o havendo a forma??o de prostan?ides, e os efeitos colaterais promovidos pelos AINES tornam limitante o seu uso. H? duas isoformas de COX: a COX-I, constitutivamente nos tecidos e respons?vel pelas fun??es fisiol?gicas; e a COX-II, induzida ap?s est?mulos inflamat?rios, ?lgicos e t?rmicos. Dessa forma, entendeu-se que o uso de AINES seletivos para a COX-II, diminuiria os efeitos adversos desses f?rmacos, uma vez que garantiria as fun??es homeost?ticas da COX-I. Atualmente, sabe-se que a COX-II tamb?m est? presente constitutivamente em alguns tecidos como o sistema nervoso central e rim. Dessa forma, todos os AINEs podem causar efeitos adversos em maior ou menor intensidade, e o grau de seletividade de cada f?rmaco ser? determinante na ocorr?ncia de rea??es indesej?veis. O objetivo desse trabalho foi avaliar o potencial analg?sico, anti-edematog?nico e antipir?tico dos principais AINES utilizados em medicina veterin?ria, os COX n?o seletivos flunixim meglumine (FM) e cetoprofeno (CT); os COX-II preferenciais meloxicam (MX) e carprofeno (CP) e o COX-II seletivo firocoxibe (FC) ap?s a administra??o oral, bem como a atividade ulcerog?nica sobre a mucosa g?strica, tendo-se assim uma avalia??o comparativa tanto de seu efeito antinociceptivo e/ou antiinflamat?rio, como de rea??es indesej?veis; subsidiando o m?dico veterin?rio cl?nico, no estabelecimento da rela??o custo/benef?cio desses f?rmacos. No teste do edema de orelha induzido pelo ?leo de cr?ton em camundongos, o CT (ID50 = 3,6 mg/kg) foi ? droga mais potente, seguido do CP e FM (ID50 = 12,3 e 17,8 mg/kg, respectivamente). O MX e FC, apesar de efetivos, mostraram baixa atividade n?o produzindo efeito suficiente com a dose m?xima de 30mg/kg, para a determina??o da ID50. Na febre induzida pelo LPS em ratos, o FC produziu atividade antipir?tica com ID50 = 2,9 mg/kg, acompanhado do CT, CP e FM (ID50 = 3,3; 3,6 e 4 mg/kg, respectivamente) e com maiores doses do MX (ID50 = 17,8 mg/kg). Avaliando o potencial analg?sico pelo m?todo das contor??es abdominais com ?cido ac?tico em camundongos, o MX foi o mais potente (ID50 = 0,09 mg/kg), seguido do FM, FC, CP e CT (ID50 = 0,4; 1,9; 2,3 e 3,6 mg/kg, respectivamente) e, utilizando estas ID50 na avalia??o da atividade ulcerog?nica em camundongos, o FC, FM e MX n?o produziram efeitos g?stricos significativos no 3? ou no 7? dia dos tratamentos. O CT e o CP promoveram ulcera??es no 3? dia, sendo o CT de forma mais intensa; n?o se observando altera??es g?stricas no 7? dia, podendo esse efeito estar relacionado ao desenvolvimento de toler?ncia aos danos causados por essa classe de drogas na mucosa. Esses resultados revelam que a atividade analg?sica da quase totalidade desses f?rmacos independe da atividade antiedematog?nica e antipir?tica, tendo o CT revelado ID50 semelhantes em todos os testes farmacol?gicos. A atividade ulcerog?nica g?strica evidenciada, teve rela??o inversa com a atividade analg?sica de todos esses f?rmacos.

Made available in DSpace on 2015-04-14T13:54:13Z (GMT). No. of bitstreams: 1 462079.pdf: 3544507 bytes, checksum: 8aa2241950201e3ad9aaa5bc2c51d167 (MD5) Previous issue date: 2014-08-27 / Background: The high prevalence of anti-inflammatory and analgesic drug use by the elderly has been widely discussed in the literature because polymedication increases the risk of adverse effects and iatrogenic and drug interactions. Anti-inflammatory and analgesic drugs are primarily used to treat pain in the elderly, who are subject to high rates of arthrosis, arthritis and rheumatism. The prescription of anti-inflammatories and analgesics in the elderly should be individualized because the pharmacokinetics and pharmacodynamics of these drugs are altered in the elderly, which can cause numerous adverse effects. However, many studies have indicated a possible antioxidant action of anti-inflammatory drugs. Some studies have suggested that anti-inflammatory drugs induce the generation of reactive oxygen species, while other studies have demonstrated that they also have antioxidant activity. Aims: We report the findings of a transversal study of the use of anti-inflammatory and analgesic drugs among a random sample of elderly patients at the Family Health Strategy (FHS) in Porto Alegre, Rio Grande do Sul, Brazil. Methods: This study is part of the The multidimensional study of the elderly in the Family Health Strategy in Porto Alegre, Brazil (EMI-SUS) conducted over the period of March 2011 to December 2012. Data collection was performed by community health workers at the subjects homes using a general questionnaire and included sociodemographic data, life conditions and habits, chronic diseases and drug use. For this study, the focus was on drugs classified as anti-inflammatory or analgesic drugs according to the Anatomical Therapeutic Chemical classification system recommended by the World Health Organization. Blood was subsequently collected by the project team at the healthcare unit where the elderly patients were registered. The plasma levels of oxidative and inflammatory markers such as insulin, homeostatic model assessment-insulin resistance (HOMA-IR), malondialdehyde (MDA), ferric reducing ability of plasma (FRAP), advanced oxidation protein products (AOPP), interleukin-6 (IL-6) and ultra-sensitivity C-reactive protein (PCR_US) were determined. Anthropometric data were measured, but only body mass index (BMI) was used in this study. Results: Among the 758 elderly patients included in this study, between 60 and 111 years old, with the prevalence of anti-inflammatory and analgesic drug use was 28.8%. Paracetamol (67.9%) and ibuprofen (31.7%) were the most commonly used drugs. Women used antiinflammatory and analgesic drugs (P = 0.022) more frequently than men. Self-rated health was related to the use of anti-inflammatory and analgesic drugs, i.e., the worse the reported health, the greater the use of these drugs (P < 0.001). Of the conditions described by the elderly, hepatic disease (P = 0.004) and arthrosis/arthritis/rheumatism were associated with the use of anti-inflammatory and analgesic drugs. In addition, we observed that the higher the usage of medicines in general, the greater the use of anti-inflammatory and analgesic drugs (P < 0.001). Gastric problems reported by this elderly cohort may be associated with chronic or occasional use of NSAIDs (P = 0.042). There was no statistically significant association between the use of NSAIDs and oxidative or inflammatory markers. Conclusion: This study demonstrates the moderate use of anti-inflammatory and analgesic drugs by elderly patients at the FHS in Porto Alegre. Although these medications are important for the management of pain and inflammation, they may interfere with the improvement of the quality of life of the elderly. Thus, anti-inflammatory and analgesic drugs should be prescribed very carefully and individually in the elderly. With regard to inflammatory and oxidative markers, it is important to emphasize that the physiological effects of NSAIDs on markers of inflammation and oxidative metabolism are poorly characterized and controversial. This is the first study to demonstrate a lack of association between NSAID use and plasma levels of oxidative, antioxidant and inflammatory markers or the HOMA-IR value. / Introdu??o: A alta preval?ncia de uso de anti-inflamat?rios e analg?sicos por idosos ? amplamente discutida na literatura devido aos riscos de efeitos adversos, iatrogenias e intera??es medicamentosas, uma vez que a maioria dos idosos ? polimedicada. A dor ? um dos principais motivos de uso desses medicamentos, principalmente devido ao alto ?ndice de artrose, artrite e reumatismo nessa popula??o. A prescri??o de anti-inflamat?rios e analg?sicos em idosos deve ser individualizada, pois a farmacocin?tica e a farmacodin?mica desses f?rmacos sofrem altera??es no organismo idoso, podendo causar in?meros efeitos adversos. Apesar de todos esses indicativos, muitos estudos v?m apontando uma poss?vel a??o antioxidante dos anti-inflamat?rios. A literatura tem sugerido que os anti-inflamat?rios induzem ? gera??o de esp?cies reativas de oxig?nio, contudo outros estudos demonstram que tamb?m podem desempenhar uma atividade antioxidante. Objetivo: Estudar o uso de anti-inflamat?rios e analg?sicos pelos idosos que frequentam a Estrat?gia Sa?de da Fam?lia (ESF) de Porto Alegre, Rio Grande do Sul, Brasil. M?todos: Estudo transversal coletado em uma amostra aleat?ria de idosos da ESF do munic?pio de Porto Alegre. Este estudo faz parte do Estudo epidemiol?gico e cl?nico dos idosos atendidos pela Estrat?gia Sa?de da Fam?lia do munic?pio de Porto Alegre (EMI-SUS), realizado durante o per?odo de mar?o de 2011 a dezembro de 2012. A coleta de dados foi realizada pelos Agentes Comunit?rios de Sa?de, em visita domiciliar, por meio de question?rio geral contendo dados sociodemogr?ficos, condi??es de sa?de, doen?as cr?nicas e h?bitos de vida dos idosos e uso de medicamentos. Para este estudo, foram inclu?dos os antiinflamat?rios e analg?sicos conforme o sistema de classifica??o Anatomical Therapeutic Chemical. Foram coletados dados antropom?tricos dos idosos e para este estudo foi utilizado o ?ndice de massa corporal (IMC). A coleta de sangue foi realizada posteriormente pela equipe do projeto na unidade de sa?de onde os idosos estavam cadastrados. Foram determinados os n?veis plasm?ticos de marcadores oxidativos e inflamat?rios, tais como insulina, HOMA-IR (homeostatic model assessment-insulin resistance), malondialde?do (MDA), habilidade de redu??o f?rrica plasm?tica ou poder antioxidante (FRAP), produto avan?ado da oxida??o proteica (AOPP), interleucina-6 (IL-6) e prote?na c reativa ultrassens?vel (PCR-US). Resultados: Foram inclu?dos 758 idosos, com idade de 50 ? 111 anos e a preval?ncia de uso de anti-inflamat?rios e analg?sicos foi de 28,8%. O paracetamol (67,9%) e o ibuprofeno (31,7%) foram os medicamentos mais utilizados. O sexo feminino utilizava com maior frequ?ncia anti-inflamat?rios e analg?sicos (P=0,022). Diante das vari?veis de sa?de, a autopercep??o de sa?de mostrou estar relacionada com o uso de anti-inflamat?rios e analg?sicos, sendo que, quanto pior a sa?de relatada, maior o uso da terap?utica (P<0,001). Entre as patologias descritas pelos idosos, a doen?a hep?tica (P=0,004) e a artrose/artrite/reumatismo (P<0,001) mostraram estar associadas ao uso de anti-inflamat?rios e analg?sicos. Foi observado que, quanto maior o uso de medicamentos em geral, maior o uso de anti-inflamat?rios e analg?sicos (P<0,001). Quanto ao uso cr?nico de anti-inflamat?rios n?o esteroidais (AINEs), verificou-se associa??o com as doen?as gastrintestinais relatadas pelos idosos (P=0,042). Quanto ? associa??o dos AINEs com os marcadores oxidativos e inflamat?rios, nada estatisticamente significativo foi encontrado. Conclus?o: Os resultados deste estudo mostram a utiliza??o moderada de anti-inflamat?rios e analg?sicos pelos idosos da ESF de Porto Alegre. Sabe-se da import?ncia desses medicamentos para o manejo da dor e da inflama??o, podendo interferir na melhoria da qualidade de vida do idoso. Por?m, a prescri??o de anti-inflamat?rios e analg?sicos deve ser feita com muita cautela e de forma individualizada nos idosos. Quanto aos marcadores inflamat?rios e oxidativos, ? importante ressaltar que os efeitos fisiol?gicos dos AINEs nos marcadores do metabolismo oxidativo e inflamat?rio ainda s?o escassos e controversos. Entretanto, este ? o primeiro estudo que demonstrou a aus?ncia de associa??o do uso de AINEs com n?veis plasm?ticos de marcadores inflamat?rios e oxidativos, poder antioxidante e HOMA-IR.

Made available in DSpace on 2015-04-14T13:32:57Z (GMT). No. of bitstreams: 1 438021.pdf: 1108728 bytes, checksum: ad26f1d3bd584ce7ee67b129ed9fc9ad (MD5) Previous issue date: 2012-01-30 / AIM : To compare the efficacy of the intravenous administration of two analgesics (morphine or ketamine) for reduction of fractures or dislocations in children.METHODS : Randomized and controlled study conducted in the emergency department of a university hospital. Patients between 3 years to 14 years and 6 months old presenting dislocation or bone fracture requiring closed reduction were included. A previous sedation was provide with midazolam and analgesia was performed in a random way: IV ketamine or IV morphine. The groups were then compared to time required to start the intervention, the duration of the reduction and immobilization, the child's cooperation during the procedure, to the satisfaction of parents and orthopedic and adverse reactions.RESULTS : Twenty-five children were included. Demographic data, type of injury and pain scores before procedure was similar in both groups. The duration of the procedure was significantly lower in the morphine group compared to the ketamine group (median 3 versus 5 minutes; < p 0.027). The median pain score of the child after the procedure was 2 in both groups. Parents (guardians children) as well as orthopedic surgeons were very satisfied in both groups (p>0,3 and >0,2). One patient in the ketamine group and 3 in the morphine group presented lower saturation with rapid reversion (p>0,2).CONCLUSION : The results support the efficacy of ketamine as compared with standard analgesics such as morphine, in facilitating the reduction of dislocations or fractures in pediatric emergency with respect to pain relief and anxiety and parental satisfaction and orthopedists. / OBJETIVO : Comparar a efic?cia de dois analg?sicos endovenosos (cetamina ou morfina) para a redu??o de luxa??es ou fraturas em crian?as.M?TODOS : Estudo randomizado e controlado, conduzido no servi?o de emerg?ncia de um hospital universit?rio. Foram inclu?dos pacientes entre 3 anos a 14 anos e 6 meses apresentando luxa??o ou fratura fechada necessitando redu??o. Era realizada seda??o pr?via com midazolam e analgesia de forma randomizada para receber cetamina ou morfina. Os grupos foram comparados em rela??o ao tempo necess?rio para iniciar a interven??o, ? dura??o da redu??o e imobiliza??o, ? coopera??o da crian?a durante o procedimento, ? satisfa??o dos pais e do ortopedista e a rea??es adversas.RESULTADOS : Vinte e cinco crian?as foram inclu?das. Dados demogr?ficos, tipo de les?o e escore de dor antes da interven??o foram similares nos dois grupos. O tempo de dura??o do procedimento foi significativamente menor no grupo morfina em rela??o ao grupo cetamina (mediana 3 versus 5 minutos; p<0,027). A mediana do escore de dor da crian?a ap?s o procedimento foi 2 em ambos os grupos. Tanto os pais quanto os ortopedistas ficaram muito satisfeitos em ambos os grupos (p>0.3 e >0,2). Um paciente do grupo cetamina e 3 do grupo morfina apresentaram queda de satura??o com r?pida revers?o (p>0,2).CONCLUS?O : Os resultados refor?am a efic?cia da cetamina, quando comparada com um analg?sico padr?o como a morfina, em facilitar a redu??o de luxa??es ou fraturas em emerg?ncia pedi?trica no que tange ao al?vio da dor e ansiedade e satisfa??o dos pais e ortopedistas.