Desenvolvimento e aplicação de método analí­tico para detecção de estimulantes em suplementos nutricionais adulterados / The development and application of analytical method for the detection of stimulants in adulterated nutritional supplements

A adição fraudulenta de ativos farmacêuticos em suplementos nutricionais é um problema mundial. É comum encontrar mensagens sobre perda de peso, aumento da capacidade intelectual e/ou física, e estímulo sexual na embalagem de suplementos adulterados com fármacos sintéticos ocultos em formulações aparentemente inofensivas para os usuários. No Brasil, a disponibilidade de dados sobre a adulteração de suplementos nutricionais é escassa. No presente trabalho, foi desenvolvido e aplicado um método analítico empregando cromatografia gasosa com detector de nitrogênio fósforo (GC-NPD) para a detecção, identificação e quantificação de estimulantes/anorexígenos não declarados nos rótulos de suplementos alimentares, tais como: cafeína, femproporex, anfepramona, fenfluramina, sibutramina, fentermina, efedrina, fenilpropanolamina, pseudoefedrina e 4- metilhexan-2-amina. A técnica de extração/solubilização com metanol foi utilizada, ressaltando a utilização de baixa quantidade de amostra, solvente e padrões de estimulantes. Após o desenvolvimento e validação do método, as análises foram aplicadas em amostras de suplementos nutricionais obtidos em lojas especializadas em suplementos, de diversas partes do estado de São Paulo (n=125). Das 125 amostras de suplemento nutricional analisadas, 38 delas (30%) apresentaram resultado positivo para alguma das substâncias de interesse, dentre elas, sibutramina, cafeína e efedrina mediante a metodologia escolhida. As amostras positivas foram posteriormente analisadas qualitativamente por LC-MS/MS, no propósito de confirmar o resultado positivo obtido. A técnica analítica empregada proporciona seletividade, linearidade, precisão, exatidão, recuperação e limites em conformidade ao objetivo que foram destinadas. Os métodos de preparo de amostra desenvolvidos e validados demonstraram ser simples, práticos, eficientes e diferenciados pelo baixo uso de amostra e solvente

The fraudulent addition of active pharmaceutical compounds in nutritional supplements is, indeed, a worldwide problem. Often, it can be found several advertisements on various supplement packaging assuring weight loss, increased intellectual and/or physical capacity and sexual stimulation. These products may have been 'spiked' with synthetic drugs containing formulations which are apparently harmless to users. In Brazil, the availability of data about adulteration of nutritional supplements is scarce. In the present work, an analytical method using gas chromatography coupled with a nitrogen-phosphorus detector (GC-NPD) was developed and applied for the detection, identification and quantification of undeclared stimulants and/or anorectic agents in food supplement labels, such as: caffeine, fenproporex, amfepramone, fenfluramine, sibutramine, phentermine, ephedrine, phenylpropanolamine, pseudoephedrine e 4- metilhexan -2- amine. The extraction/solubilization with methanol presented satisfactory results, emphasizing the use of low amount of sample, solvent and standards of analytes. After the development and validation, the method was applied in samples of nutritional supplements obtained from specialty stores in various parts of the state of São Paulo (n = 125). From the 125 nutritional supplement samples analyzed, 38 of them (30%) presented positive results for some of the substances of interest, among them sibutramine, caffeine and ephedrine according to the chosen methodology. The positive samples were subsequently analyzed qualitatively by LCMS / MS, in order to confirm the positive result obtained. The analytical technique employed provides selectivity, linearity, precision, accuracy, recovery and limits in accordance with the intended purpose. The sample preparation methods developed and validated to be simple, practical, efficient and differentiated by the low sample and solvent usage

Prescrição, dispensação e regulação do consumo de psicotrópicos anorexígenos em Belo Horizonte, Minas Gerais, Brasil / Prescription, dispensing, and regulation of psychoactive anorexigenic drugs in Belo Horizonte, Minas Gerais, Brazil

Estudo retrospectivo, realizado na cidade de Belo Horizonte, Minas Gerais, Brasil, para avaliar indicadores de dispensação e consumo de substâncias anorexígenas. Ocorreu em duas etapas: na primeira, foram analisadas 2.906 das 168.237 notificações de receitas aviadas por estabelecimentos farmacêuticos da cidade, em 2003. Observou-se uma baixa qualidade nas notificações. O consumo projetado foi de 19,75 DDD/mil habitantes/dia. A substância mais consumida foi o fenproporex (59,8 por cento). Uma farmácia foi responsável por 39,8 por cento das dispensações. Na segunda etapa, foram analisados 14.554 registros do livro de receituário geral da farmácia que mais dispensou tais produtos, no período de abril a agosto de 2005. Os anorexígenos responderam por 9,2 por cento das manipulações e 91,8 por cento deles foram prescritos para uso concomitante com outra substância: 43 por cento com clordiazepóxido, 50,6 por cento com fluoxetina, 7,5 por cento com outro anorexígeno e 28,2 por cento com bromazepam. Os resultados observados sugerem um uso indiscriminado e irracional de anorexígenos neste município, sendo fundamental aprimorar a regulação do mercado de produtos manipulados. Para tanto, é necessário uma melhor compreensão do papel da farmácia nessa regulação e o papel dos prescritores no uso racional dessas substâncias.

This retrospective study in Belo Horizonte, Minas Gerais, Brazil, aimed to provide indicators on the sale and consumption of anorexigenic substances. During the first stage, 2,906 of 168,237 prescriptions received by pharmacies in 2003 were analyzed, showing low quality of prescriptions. Projected consumption in defined daily doses was 19.75 DDD/1,000 inhabitants/day in 2003. Fenproporex (59.8 percent) was the most widely consumed drug. One pharmacy was responsible for 39.8 percent of the pharmaceutical sales. During the second stage, 14,554 sales records from this "blockbuster" pharmacy were analyzed, from April to August 2005; 9.2 percent of sales were for anorexigenic products, 91.8 percent of which prescribed in association with another substance. The data suggest irrational use of anorexigenic drugs by these consumers and highlight the need for proper regulation of these products. It is important to understand both the role of pharmacies in this regulation and that of physicians in the rational use of these substances.

TSH levels associated with slimming pill use in a population-based study of brazilian women

OBJECTIVE: To determine the consumption of slimming pills (SP) and its association with TSH levels. RESEARCH METHODS AND PROCEDURES: A survey was carried out in Rio de Janeiro (about 5 million inhabitants), Brazil, from June 2004 to April 2005. Households (1,500) were selected using three-stage probability sampling. Women were asked about use of SP, and blood sample was collected. Women were classified as users of SP any time in life, but not in previous two months (n = 293), current users (n = 150), and never users (n = 853). Weighted multivariate regression analyses compared TSH levels among these groups of users. RESULTS: The frequency of use of SP any time in life was 34 percent and the use in the previous two months was 11 percent. Both frequencies were greater among younger and obese women, and among those of high socioeconomic level (p-value < 0.001). TSH level was statistically lower among current users of SP (1.96 mUI/ml; 95 percentCI = 1.93-1.98) compared to previous users 2.83 mUI/ml (95 percentCI = 2.13-3.02) and never users 2.59 mUI/ml (95 percentCI = 2.20-3.21). These differences were still statistically significant after adjusting for age and body mass index. CONCLUSIONS: Use of SP decreased TSH levels among Brazilian women.

OBJETIVO: Determinar a freqüência de uso de fórmulas para emagrecer e sua associação com níveis de TSH. METODOLOGIA: Pesquisa realizada no Rio de Janeiro (5 milhões de habitantes), Brasil, de junho de 2004 a abril de 2005. A população de estudo foram mulheres com 35 anos ou mais, residentes em domicílios particulares permanentes do município do Rio de Janeiro não grávidas e não lactantes. A amostra de domicílios foi obtida por amostragem probabilística conglomerada em três estágios de seleção. As mulheres tiveram amostras de sangue coletadas e responderam a questões sobre uso de fórmulas, chás ou remédios para emagrecer. Quanto ao uso de fórmulas as mulheres foram classificadas em usuárias alguma vez na vida (n = 293), usuárias nos últimos dois meses (n = 150) e não usuárias (n = 853). Os níveis de TSH desses grupos foram comparados através de análise de regressão multivariada, levando em conta o desenho da amostra. RESULTADOS: O uso de fórmulas alguma vez na vida foi relatado por 34 por cento das mulheres e 11 por cento relataram tê-las consumido nos últimos dois meses. As freqüências foram maiores entre as mulheres mais jovens e obesas e de nível sócio-econômico mais elevado (valor de p < 0,001). Os níveis de TSH foram estatisticamente menores entre as usuárias de fórmulas (1,96 mUI/ml; IC 95 por cento = 1,93-1,98) comparados com usuárias prévias 2,83 mUI/ml (IC 95 por cento = 2,13-3,02) e não usuárias 2,59 mUI/ml (IC 95 por cento = 2,20-3,21). As diferenças entre os grupos mantiveram-se estatisticamente significantes após o ajuste por idade e índice de massa corporal. CONCLUSÃO: O uso de fórmulas para emagrecer diminuiu os níveis de TSH em mulheres brasileiras.

Tolerability and effectiveness of fluoxetine, metformin and sibutramine in reducing anthropometric and metabolic parameters in obese patients / Tolerabilidade e eficácia da fluoxetina, metformina e sibutramina na redução de parâmetros antropométricos e metabólicos em pacientes obesos

The aim of this study is to assess the effects of sibutramine (S) 15 mg/day, fluoxetine (F) 60 mg/day, and metformin (M) 1,700 mg/day, as an adjunct therapy to a 1,500 kcal/day diet, in reducing anthropometric and metabolic parameters. S (n= 8), F (n= 9), and M (n= 8) were compared to placebo (n= 10) in 35 obese patients in a 90-day trial. Side effects were also studied during the treatment. The data demonstrated that F therapy resulted in a greater average reduction in BMI (11.0 percent), weight (10.0 percent), abdominal circumference (11.0 percent) and percentfatty-tissue (12.8). An elevation in HDL-cholesterol (25.8 percent) and a reduction in average triglyceride levels (28.3 percent) were also shown. S presented a 7.91 percent reduction in the abdominal circumference and a 9.65 reduction in percentfatty-tissue was also found. M group presented reductions in BMI (4.03 percent), waist circumference (6.92 percent), HOMA (23.5 percent) and blood pressure (6.08 percent in systolic and 2.08 percent in diastolic). In general, the three drugs can be considered well tolerated. We concluded that F and S demonstrated a greater mean reduction in anthropometric and metabolic parameters when compared to M, however all of them are useful for that purpose, when the subjectsÆ characteristics are considered.

O objetivo deste estudo foi avaliar o efeito da sibutramina (S) 15 mg/dia, fluoxetina (F) 60 mg/dia, e metformina (M) 1.700 mg/dia, associadas a uma dieta de 1.500 kcal/dia, na redução de parâmetros antropométricos e metabólicos. S (n= 8), F (n= 9) e M (n= 8) foram comparadas ao placebo (n= 10) em 35 pacientes obesos durante 90 dias de tratamento. As reações adversas também foram avaliadas durante o tratamento. O grupo F demonstrou uma redução no IMC (11,0 por cento), peso (10,0 por cento), circunferência abdominal (11,0 por cento) e por cento de tecido adiposo (12,8). Também foram observados um aumento nos níveis de HDL-colesterol (25,8 por cento) e uma redução nos níveis de triglicérides (28,3 por cento), no grupo F. O grupo S apresentou uma redução de 7,91 por cento na circunferência abdominal e de 9,65 na por cento de tecido adiposo. Já o grupo M apresentou reduções no IMC (4,03 por cento), circunferência abdominal (6,92 por cento), HOMA (23,5 por cento) e pressão arterial (6,08 por cento na sistólica, 2,08 por cento na diastólica). Os três fármacos analisados foram bem tolerados durante o tratamento. Concluímos que a F e a S demonstraram maior eficácia na redução dos parâmetros antropométricos e metabólicos dos pacientes obesos quando comparadas à M, entretanto todas podem ser prescritas para essa finalidade, desde que sejam consideradas as características individuais dos pacientes.

Effects on Weight Reduction and Safety of Short-Term Phentermine Administration in Korean Obese People

The phentermine, an appetite suppressant, has been widely applied in Korea since 2004. However, there have been relatively few reports about the efficacy and the safety of phentermine in Korea. The aim of this study is to verify the effect of phentermine on weight reduction and the safety in Korean patients. This randomized, double-blind, placebo- controlled study had been performed between February and July, 2005, in Seoul on 68 relatively healthy obese adults whose body mass index was 25 kg/m2 or greater. They received phentermine-HCl 37.5 mg or placebo once daily with behavioral therapy for obesity. The primary endpoints were the changes of body weight and waist circumference from the baseline in the intention-to-treat population. Mean decrease of both body weight and waist circumference in phentermine-treated subjects were significantly greater than that of placebo group (weight: -6.7 +/- 2.5 kg, p < 0.001; waist circumference: -6.2 +/- 3.5 cm, p < 0.001). Significant number of subjects in phentermine group accomplished weight reduction of 5% or greater from the baseline and 10% or more (p < 0.001). There were no significant differences in systolic and diastolic blood pressure between the groups (p = 0.122 for systolic BP; p = 0.219 for diastolic BP). Dry mouth and insomnia were the only statistically significant adverse events that occurred more frequently in phentermine group. Most side effects of phentermine were mild to moderate in intensity. Short-term phentermine administration induced significant weight reduction and reduction of waist circumference without clinically problematic adverse events on relatively healthy Korean obese people.

Inappropriate weight management among Thai women consuming anorectics prescribed by private clinics in Bangkok.

This cross-sectional survey was conducted by a 2-stage sampling design. A total of 250 women, aged > or = 18 years, were recruited from 10 randomly chosen private clinics located around Bangkok with a license for possession and utilization of anorectic drugs, the psychotropic substances in category II. Body mass index was calculated at the time of survey. The prevalence of obesity, based on the proposed classification by body mass index in Asian adults, among the participants was 23.2% (95% CI: 18.0%-28.4%). Only 79 (31.6%) and 72 (28.8%) reported having low-calorie diets and increasing physical activities, respectively, both of which were recommended as the main part of comprehensive weight control. Cosmetic purpose was the main reason given by most participants (84.0%) to enter current weight-control treatments. Interestingly, most of the non-obese individuals (82.8%) misperceived themselves as being obese. These findings suggested that the inappropriate use of anorectic drugs among Thai women was a significant public health concern. Misperception of bodyweight status may contribute to the misuse of such anorectic drugs. The result would alarm the Food and Drug Administration, Ministry of Public Health to evaluate and revise the measures of the anorectic drug disposal. Further qualitative methods are recommended to investigate for body-image misconception, weight-control behavior among various populations.

Clinical evaluation of sibutramine in obese type 2 diabetic patients refractory to dietary management.

MATERIAL AND METHODS: An open, non-comparative study was carried out to assess the efficacy and toleration profile of sibutramine, a new antiobesity drug, in promoting weight loss in obese type 2 diabetes mellitus subject who failed to reduce weight after strict dietary control. Twenty seven patients completed the study. Sibutramine was started as a single morning dose of 10 mg and was subsequently increased to 15 mg daily if weight loss was not satisfactory. The total duration of the study was twelve weeks with followup at every four weeks. Effect of drug was monitored in terms of weight reduction, changes in body mass index, waist circumference, hip circumference, waist/hip ratio and other metabolic parameters. A fixed dietary prescription and concomitant therapy with drugs, if required and not likely to interfere with the trial therapy, was permitted but was not changed during the study period. RESULTS: At the end of 12 week, mean weight reduction in study subjects was 4.16 kg (p < 0.001), the corresponding BMI decreased by 1.6 (p < 0.0001) and hip circumference by 3.68 (p < 0.001). However, there was no significant change in fasting blood glucose and Hb(A1c) values. CONCLUSION: The study indicates sibutramine to be an effective and well tolerated agent leading to significant reduction in parameter of obesity in obese type 2 diabetic subjects.

A comparative study of the anorectic and behavioral effects of fenproporex on male and female rats

The anorectic and behavioral effects of fenproporex (Fenp, 10 mg/kg, ip) and methamphetamine (Met, 2.5 mg/kg, ip), a prototypical example of an amphetamine-like drug, were studied in male and female Wistar rats (5 and 3 months of age, respectively, at the beginning of the experiments) after acute (immediately after a single dose) or chronic treatment (after 60 days of administration). For the evaluation of the experimental parameters six groups of eight rats each were utilized for food intake and stereotyped behavior and six groups of nine rats each for body weight and motor activity. Similar anorectic effects (decreased food intake in grams: saline(Sal): 12.8 ñ 2.5, Met: 4.7 ñ 4.0, and Fenp: 4.4 ñ 20; decreased weight gain: Sal: 38 ñ 10, Met: 25 ñ 1.0, and Fenp: 27 ñ 3.0) were induced by both drugs in male rats. Female rats, however, required larger doses (20 mg/kg Fenp and 5.0 mg/kg Met) for a complete blockade of food intake. The behavioral tests were carried out 30, 60, 120, 180 and 300 min after drug administration and on day 1 and day 60 immediately after the treatment, for stereotypy and motor activity, respectively (male rats: Met: 3.8 ñ 0.3, Fenp: 6.0 ñ 0.9, and female rats: Met: 15.4 ñ 1.9, Fenp: 9.7 ñ 1.3). Though stereotyped behavior such as sniffing, continuous licking, and false bites was observed in all animals, this was more evident and prolonged in female rats. Both drugs also increased motor activity (male rats, acute treatment: Met: 608 ñ 419, Fenp: 677 ñ 354; chronic treatment: Met: 701 ñ 423, Fenp: 908 ñ 479; female rats, acute treatment: Met: 817 ñ 350, Fenp: 1177 ñ 282; chronic treatment: Met: 623 ñ 274, Fenp: 1511 ñ 573) with female rats once again showing greater sensitivity both after acute and chronic treatment. Our data indicate that fenproporex, like methamphetamine, has a stimulating effect on the central nervous system, indicating an action on the dopaminergic systems. These data further suggest that its therapeutic use as an appetite moderator should be prescribed with caution, especially to women, since, at least in the species studied, the female organism seems to show higher susceptibility to the central effects of this substance.

Drogas anorexígenas en el tratamiento de la obesidad / Anorexigenic drugs in the treatment of obesity

Obesity is highly prevalent and has several adverse effects on health. Its treatment is thus warranted and must aim to modify dietary and physical activity habits. The opinion of this association is that anorexigenic drugs with cathecolaminergic action (diethylpropion, phentermine, mazindol and phenylpropanolamine) or serotoninergic action (fenfluoramine and fluoxetine) may be used in moderate or severe obesity (BMI >30 kg/m2) after a complete clinical assessment and in the context of an integral medical treatment. This association recommends a close surveillance of the use of these drugs, specially when formulated as non-propietary prescriptions

Anorexia nerviosa: estudio clínico-fenomenológico de siete casos / Anorexia nervosa: clinical and phenomenological study of 7 cases

La anorexia nerviosa es un importante problema de salud. Estimaciones de la tasa de morbilidad y mortalidad fluctúan entre el 4 por ciento y el 18 por ciento. Esta enfermedad es más frecuente en mujeres y la edad de comienzo es la adolescencia. Se estudiaron 7 pacientes que cumplían los criterios diagnósticos del ICD-9 utilizando el método clínico fenomenológico. Se describen los fenómenos y las características psicopatológicas comunes a todas estas pacientes y su actitud frente a la enfermedad son reportados en este estudio. Los hallazgos sugieren que la anorexia nerviosa es una entidad clínica psiquiátrica con sus propios hechos psicopatológicos, las que claramente difieren de otros desórdenes psiquiátricos que presentan perturbación del apetito y disminución del peso corporal. Finalmente, nuestra impresión clínica es que las pacientes con anorexia nerviosa desarrollan inicialmente su hábito alimenticio por una necesidad de obtener una imagen corporal ideal la que posteriormente daría paso a una búsqueda permanente de la sensación de bienestar, la que alcanzan pero es inestable y frágil