Thesis (M.S.)--Rutgers University, 2007. / "Graduate Program in Nutritional Sciences." Includes bibliographical references (p. 38-45).

The stereo-chemistry, structure activity relationships and the metabolism of the anorectic drug, diethylpropion hydrochloride, have been reviewed briefly, together with the analytical methods for the determination of this drug and its metabolites in biological fluids. In addition, the physico-chemical properties, mode of action, pharmacology and uses of the metabolites have been presented. A comprehensive review on general principles of salivary excretion of drugs and their therapeutic drug monitoring in saliva with relevant published data on saliva/plasma drug concentration relationships has been outlined. Sensitive and specific assay procedures, based on gas-liquid chromatography for the identification, separation and determination of diethylpropion and its two major metabolites i.e. ethylaminopropiophenone (11) and diethylnorpseudoephedrine (IV) in aqueous and biological fluids, have been developed. These methods were used to study the urinary excreUon as well as saliva and plasma levels of the two major metabolites and, where possible, the unchanged drug, in man. Sustained release pellets with diffusion rate-controlled membranes were employed to control the rate of input into the body by oral or rectal route of administration. Urinary excretion data and plasma levels of metabolites 11 and IV in volunteers, where the urine was controlled at an acidic pH, were used for the evaluation of the bioavailabilities of different dosage forms of diethylpropion hydrochloride. The concentrations of metabolites 11 and IV were also measured in saliva and in plasma after administration of the drug in different doses and dosage forms: relationships between saliva and plasma concentrations (S/P) and between urinary excretion rates and plasma concentrations (U/P) were developed for each of the two metabolites during plateau levels after oral administration of the sustained release pellets (Lot R 7773). The potential use of salivary excretion of the metabolites as an index to monitor their plasma levels and bioavailabilities, was examined. The distinct advantage of using a subdivided controlled release system (i. .e. sustained release pellets) to a single unit sustained release tablet (erosion-core type) in relation to influence of the physical presence of food on the rate and extent of absorption has been demons t rated . It was found that the route of administration (oral or rectal) did not significantly affect the bioavailability of the sustained release pellets. The study also involved the investigation of the release of the drug from the pellets. Because the release control step was diffusion, no significant influences on dissolution rates were observed with the use of different dissolution test models and agitation intensities. The influence of the concentration and composition (presence of cations viz. Na+ and K+ i~r anions viz . phosphate and borate) of the dissolution medium on the release of the drug from sustained release pellets, was also studied. Any potential changes in the dissolution pattern on storage of the pellets under different conditions (4°C, room temperature and 37°C) ovrr, a period of at least one year, were investigated. The in vitro and in vivo correlations of two lots of sustained release pellets, each exhibiting different dissolution profiles, and administered rectally and orally, were developed: the in vitro data on the free drug were related to the sum of the urinary excretion data of metabolites II and IV. An attempt to use an empirical approach to predict urinary excretion rate profiles of metabolite II after oral administration of the sustained release pellets, was promising; the calculated profiles were reasonably comparable with those of in vivo studies. However, the complete validity of such equations needs further investigations. / Thesis (Ph.D.)-University of Durban-Westville, 1984.

The pineal gland has become the subject of considerable investigation as it provides a productive experimental model for studying circadian rhythms and regulation of end organs. In the rat, the pineal gland provides a convenient model for investigating the noradrenergic receptor system and the effects of various drugs on this system. The effect of appetite suppressants on the rat pineal gland function is described. Appetite suppressants increase melatonin synthesis in organ cultures of rat pineal glands. This effect appears to be mediated by noradrenaline acting on β-adrenoceptors on the pinealocyte membrane. When β-adrenoceptors are blocked, the appetite suppressant-induced rise in melatonin synthesis is prevented. Depletion of noradrenaline in sympathetic nerve terminals also prevented the appetite suppressant-induced rise in melatonin synthesis. Activation of β-adrenoceptors is followed by a rise in N-acetyltransferase activity via a cyclic adenosine monophosphate second messenger system. The effect of appetite suppressants on the activity of liver tryptophan pyrrolase was also investigated. The activity of this enzyme is an important determinant of tryptophan availability to the brain and consequently of brain serotonin levels. The results show that appetite suppressants inhibit both holoenzyme and total enzyme activities of tryptophan pyrrolase. This finding suggests that appetite suppressants may act by inhibiting tryptophan pyrrolase activity thereby increasing brain serotonin, a phenomenon known to be associated with anorexia. There are two possible mechanisms by which appetite suppressants inhibit tryptophan pyrrolase activity. Firstly, these agents, being drugs of dependence, may increase liver NADPH concentrations which inhibit pyrrolase activity. Secondly, appetite suppressants may act on the pineal gland to stimulate melatonin synthesis. Melatonin inhibits pyrrolase activity in a dose-dependent manner. This inhibition will elevate plasma tryptophan levels which result in a rise in brain serotonin synthesis. The present study suggests a possible relationship between the pineal gland and appetite centres in the hypothalamus. Melatonin may have a direct effect on appetite centres since food restriction is associated with an increased melatonin binding in the hypothalamus. If this possible relationship can be extended, melatonin can open new possibilities for the control of food intake and consequently, of pathological obesity.

This study explored the possibility that some individuals with alcohol and amphetamine addictions are initially motivated to use alcohol and amphetamines because of underlying issues involving body dissatisfaction and weight reduction associated with Anorexia and Bilimia Nervosa. Current literature reveals similarities among chemical dependencies and eating disorders.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-09-14T11:30:48Z No. of bitstreams: 1 eduardoluizmendoncamartins.pdf: 956113 bytes, checksum: e8e88eb48b6a69981a3291e3d3744bcc (MD5) / Approved for entry into archive by Diamantino Mayra (mayra.diamantino@ufjf.edu.br) on 2016-09-26T20:17:11Z (GMT) No. of bitstreams: 1 eduardoluizmendoncamartins.pdf: 956113 bytes, checksum: e8e88eb48b6a69981a3291e3d3744bcc (MD5) / Made available in DSpace on 2016-09-26T20:17:11Z (GMT). No. of bitstreams: 1 eduardoluizmendoncamartins.pdf: 956113 bytes, checksum: e8e88eb48b6a69981a3291e3d3744bcc (MD5) Previous issue date: 2011-03-28 / A obesidade é um grave problema de saúde pública em nosso país, com sua prevalência crescendo em níveis epidêmicos. O grau de obesidade está diretamente relacionado com o risco de morbimortalidade. O tratamento farmacológico deve ser precedido de uma mudança de hábitos alimentares e prática regular de atividades físicas. Os medicamentos só devem ser utilizados sob supervisão médica e após uma avaliação criteriosa da relação risco-benefício, para cada paciente especificamente. Em 2005, o Brasil foi o maior consumidor mundial per capita de anfetaminas com finalidade emagrecedora. Estudos anteriores sugerem que as farmácias de manipulação são responsáveis pela maior porcentagem de notificações referentes a supressores de apetite. O presente estudo avalia as dispensações de psicotrópicos anorexígenos durante o ano de 2009 em Juiz de Fora, por meio das informações obtidas dos boletins de consumo enviados mensalmente (RMNRB2) à VISA municipal e de dados obtidos no SNGPC (ANVISA). De 7.759 notificações de psicotrópicos anorexígenos, 93,3% foram dispensadas por farmácias de manipulação e somente 6,7% por drogarias. Do total, 55,4% foram da substância anfepramona, seguido de 33,1% referentes à femproporex e 11,5% de mazindol. Dos 189 médicos que emitiram as prescrições analisadas, 57% não tinham especialidade cadastrada no CRM. Sete profissionais foram responsáveis por 6.492 dispensações no ano, correspondendo a 83,7% do total. O profissional com maior número de prescrições teve 3.535 prescrições dispensadas, correspondendo a 45,6% de todas as prescrições do período analisado. Das 3.535 prescrições de substâncias psicotrópicas anorexígenas emitidas por esse profissional, todas foram dispensadas em farmácias, sendo 99,5% em um único estabelecimento. As prescrições desse profissional correspondem a 94,3% de todo o movimento de dispensações de anorexígenos efetuadas no período analisado, nesse estabelecimento. Comparando com o relatório da ANVISA referente ao consumo no país, no mesmo período, as três substâncias apresentam um consumo maior em Juiz de Fora e microrregião, em Dose Diária Definida/mil habitantes/ano. O cenário mostra a dispensação de psicotrópicos anorexígenos como um problema relevante de saúde coletiva e indica a necessidade de reavaliação dos critérios de monitoramento de sua prescrição, dispensação e consumo. / Obesity is a serious public health problem in Brazil, with prevalence figures increasing at epidemic rates. The degree of obesity is directly related to the risk of morbidity and mortality. A pharmacological approach must always be preceded by a change of eating habits along with the regular practice of physical exercises. Drugs should only be used under medical supervision and after a careful assessment of the individualized risk-benefit ratio. In 2005, Brazil had the world´s largest per capita consumption of amphetamines for weight loss. Previous studies have suggested that magistral pharmacies are responsible for the largest percentage of notifications referring to appetite suppressants. This study assesses the dispensations of appetite-suppressant psychotropics during the year 2009, in Juiz de Fora, through information obtained from the municipal sanitary surveillance authority (consisting of monthly consumption bulletins [RMNRB2] and data from the Brazilian sanitary surveillance agency [ANVISA]). Of the 7,759 notifications of drugsuppressant psychotropics, 93.3% were dispensed by magistral pharmacies, while only 6.7% were dispensed by drugstores. Of the total, 55.4% were of amphepramone, followed by 33.1% of fenproporex and 11.5% of mazindol. The large majority of the prescribing physicians did not have their specialty registered with the Regional Medical Council (57%). Seven physicians were responsible for 6,492 dispensed prescriptions, accounting for 83.7% of the total. A single physician had been responsible for 3,535 dispensed prescriptions, corresponding to 45.6% of all prescriptions during the study period. Of the 3,535 prescriptions of appetitesuppressant psychotropics signed by this physician, 99.5% were dispensed by a single magistral pharmacy. The prescriptions signed by this physician corresponded to 94.3% of all appetite-suppressants dispensed by this pharmacy during the study period. Compared with the ANVISA report, referring to the national consumption during the same period, the three substances had a greater consumption in Juiz de Fora (daily defined dose/thousand inhabitants/year). This scenario points to the dispensation of appetite-suppressant psychotropics as a relevant public health issue, indicating the need to reassess the criteria guiding the monitoring of their prescription, dispensation and consumption.

Made available in DSpace on 2015-07-22T20:50:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-05-27 / Introdução/Objetivo: Os fatores orexígenos e anorexígenos e a Taxa Metabólica de Repouso (TMR) desenvolvem um importante papel no controle e regulação do balanço energético e estão diretamente relacionados com a obesidade. Com base nesta relação, o objetivo desta pesquisa foi verificar os efeitos do tratamento multidisciplinar de longo prazo nos fatores orexígenos e anorexígenos e na TMR em adolescentes obesos. Metodologia: No presente estudo foram selecionados 20 adolescentes obesos (11 meninas e 9 meninos), com idade entre 14 e 19 anos. Os critérios de inclusão foram o IMC percentil > 95 de acordo com o Centers for Disease Control and Prevention e estágio de maturação sexual pós púbere. Os fatores orexígenos e anorexígenos foram avaliados por radioimunoensaio. A TMR foi mensurada por calorimetria indireta, a composição corporal por Pletismografia e a gordura visceral e subcutânea por Ultra-sonografia. Resultados: Após 12 meses de intervenção, os adolescentes obesos apresentaram diminuição significativa na massa corporal total, no IMC, na gordura corporal (% e em kg,), na massa magra (kg), e na gordura visceral e subcutânea. O grupo não apresentou diminuição significativa da TMR. Os fatores anorexígenos diminuíram significativamente e o MCH aumentou ao término da terapia. Conclusão: Podemos concluir que a terapia multidisciplinar de longo prazo foi efetiva para melhorar a composição corporal, os fatores orexígenos e anorexígenos, contribuindo para o controle da obesidade e do balanço energético. Palavras-Chave: Fatores orexígenos e anorexígenos; taxa metabólica de repouso; adolescente obeso; terapia multidisciplinar. / Background/Aims: anorexigenic and orexigenic factors and resting metabolic rate (RMR) play an important role in the energy balance and they are directly related to obesity. In this way, it was verified the effects of long-term multidisciplinary therapy on orexigenic and anorexigenic factors and resting metabolic rate in obese adolescents. Methods: Twenty obese adolescents (11 girls and 9 boys) aged between 14 and 19 years, BMI > 95th percentile of CDC, were submitted to intensive long-term multidisciplinary therapy during 12 months. Orexigenic and anorexigenic factors concentrations were measured by a radioimmunoassay (RIA) kit. RMR was measured by indirect calorimetry. Body composition was measured by pletismography, and visceral and subcutaneous fat were analyzed by ultrassonography. Results: After one year of multidisciplinary therapy, the obese adolescents presented a significant decrease in body mass (p<0.001), BMI (p<0.001), fat mass (kg and %), lean mass (kg), subcutaneous and visceral fat. The group did not decrease significantly in RMR and RMR/FFM. The anorexigenic factors (leptin and alpha- MSH concentrations) decreased significantly. The orexigenic neuropeptide (MCH) increased by the end of the multidisciplinary therapy. Conclusion: Our investigation demonstrated that long-term multidisciplinary therapy was effective to improve body composition, anorexigenic and orexigenic factors contributing to obesity control. / TEDE / BV UNIFESP: Teses e dissertações