RESUMO
Many obese patients are exposed to hypolipidemic and serotonin-norepinephrine reuptake inhibitor (SNRI) drugs. Statins are one of the most marketed drugs in the world to treat dyslipidemia, while sibutramine, a SNRI drug, is prescribed in some countries to treat obesity and is detected as an additive in many adulterated weight loss supplements marketed worldwide. Previous studies reported adverse effects of isolated exposure to these drugs on male rat reproductive parameters. In the present work, we further investigated male reproductive toxicity of these drugs, administered in isolation or combination in adult rats for a longer period of treatment. Adult male rats (90 days) were treated (gavage) for 70 days with saline and dimethyl sulfoxide (control), sibutramine (10 mg/kg), rosuvastatin (5 mg/kg), or rosuvastatin combined with sibutramine. Sibutramine alone or with rosuvastatin, promoted a reduction in food intake and body weight gain, weight of the epididymis, ventral prostate and seminal vesicle; as well as decreased sperm reserves and transit time through the epididymis; androgen depletion; and increased index of cytoplasmic droplet. The rosuvastatin-treated group showed reduced frequency of ejaculation. Exposure to this drug alone or combined with sibutramine impaired epididymal morphology. Co-exposed rats had altered epididymal morphometry, and seminal vesicle and testis weights. The rats also showed decreased fertility after natural mating and a trend toward a delay in ejaculation, suggesting a small synergistic effect of these drugs. Given the greater reproductive efficiency of rodents, the results obtained in the present study raise concern regarding possible fertility impairment in men taking statins and SNRI drugs.
Assuntos
Ciclobutanos/toxicidade , Ciclobutanos/uso terapêutico , Obesidade/tratamento farmacológico , Fenômenos Reprodutivos Fisiológicos/efeitos dos fármacos , Rosuvastatina Cálcica/toxicidade , Rosuvastatina Cálcica/uso terapêutico , Testículo/efeitos dos fármacos , Adulto , Animais , Humanos , Masculino , Modelos Animais , Ratos , Ratos WistarAssuntos
Adjuvantes Imunológicos/uso terapêutico , Alopecia em Áreas/terapia , Ciclobutanos/uso terapêutico , Ciclopropanos/uso terapêutico , Imunoterapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Hospitais Universitários , Humanos , Masculino , México , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Antiobesity pharmacotherapy remains the main point of disagreement among both scientists and regulators. This is probably due to small sample sizes, high levels of heterogeneity, and low methodological quality. For many years, Brazil was one of the largest consumers of appetite suppressants worldwide, with evidence of irrational use of this drug class. Therefore, the country was the scene of a debate that divided the Brazilian Health Surveillance Agency (Anvisa - Agência Nacional de Vigilância Sanitária) and medical societies over the maintenance record of diethylpropion, mazindol and fenproporex. In this context, this commentary presents new arguments to contribute to the discussion, as well as recommendations for future studies.
Assuntos
Depressores do Apetite/uso terapêutico , Dietilpropiona/uso terapêutico , Mazindol/uso terapêutico , Obesidade/tratamento farmacológico , Anfetaminas/uso terapêutico , Brasil , Ciclobutanos/uso terapêutico , Aprovação de Drogas , Humanos , Medição de Risco/tendências , Resultado do TratamentoRESUMO
Vasovagal or neurocardiogenic syncope is a common clinical situation and, as with other entities associated with orthostatic intolerance, the underlying condition is a dysfunction of the autonomic nervous system. This article reviews various aspects of vasovagal syncope, including its relationship with orthostatic intolerance and the role of the autonomic nervous system in it. A brief history of the problem is given, as well as a description of how the names and associated concepts have evolved. The response of the sympathetic system to orthostatic stress, the physiology of the baroreflex system and the neurohumoral changes that occur with standing are analyzed. Evidence is presented of the involvement of the autonomic nervous system, including studies of heart rate variability, microneurography, cardiac innervation, and molecular genetic studies. Finally, we describe different studies on the use of beta-blockers and norepinephrine transporter inhibitors (sibutramine, reboxetine) and the rationality of their use to prevent this type of syncope.
El síncope vasovagal o neurocardiogénico es una situación clínica común, y así como en otras entidades asociadas con la intolerancia ortostática, la condición de base es una disfunción del sistema nervioso autónomo. En este artículo se revisan diversos aspectos sobre el síncope vasovagal, incluyendo su relación con la intolerancia ortostática y el papel que juega el sistema nervioso autónomo. Se da una breve reseña histórica del problema, así como una descripción de la forma en que han evolucionado los términos y conceptos asociados al mismo. Se hace un análisis sobre la respuesta del sistema nervioso simpático al estrés ortostático, la fisiología del sistema barorreflejo y los cambios neurohumorales que ocurren. Se muestra evidencia sobre el papel del sistema nervioso autónomo, incluyendo estudios sobre variabilidad de la frecuencia cardiaca, microneurografía, inervación cardiaca y estudios genéticos moleculares. Finalmente, se describen diferentes estudios sobre el uso de betabloqueadores e inhibidores del transportador de noradrenalina (sibutramina, reboxetina) y la justificación de su uso en la prevención de este tipo de síncope.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/antagonistas & inibidores , Sistema Nervoso Simpático/fisiopatologia , Síncope Vasovagal/fisiopatologia , Barorreflexo , Ciclobutanos/farmacologia , Ciclobutanos/uso terapêutico , Frequência Cardíaca/fisiologia , Humanos , Biologia Molecular , Morfolinas/farmacologia , Morfolinas/uso terapêutico , Reboxetina , Síncope Vasovagal/tratamento farmacológicoRESUMO
OBJECTIVE: To evaluate the effect of sibutramine on weight loss in obese adolescents. SUBJECTS AND METHODS: A double-blind controlled study lasting 13 months. The study included 73 obese adolescents of both sexes aged between 10 and 18 years. Laboratory tests and imaging studies were performed before, during wash-out, and at the end of 13 months. RESULTS: The percentage of patients who lost 10% of their initial weight in the placebo group was 46%, and in the sibutramine group was 75%. When placebo was used, average weight rose by 1.61 kg, and BMI decreased by 0.24 kg/m(2) whereas with the use of sibutramine, weight decreased by 4.47 kg, and average BMI decreased, 2.38 kg/m(2), with p < 0.001. CONCLUSIONS: Sibutramine induced significantly more weight loss in obese adolescents compared with placebo, without significant side effects. The weight loss curve was different depending on the moment sibutramine was introduced. This finding indicates that the best time to start sibutramine is when adhesion begins to fail.
Assuntos
Depressores do Apetite/uso terapêutico , Ciclobutanos/uso terapêutico , Obesidade Infantil/tratamento farmacológico , Redução de Peso/efeitos dos fármacos , Adolescente , Depressores do Apetite/efeitos adversos , Glicemia/análise , Índice de Massa Corporal , Criança , Colesterol/sangue , Estudos Cross-Over , Ciclobutanos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Insulina/sangue , Leptina/sangue , Masculino , Segurança do Paciente , Obesidade Infantil/sangue , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
Chemokines are small proteins that control several tissue functions, including cell recruitment and activation under homeostatic and inflammatory conditions. CXCL8 (interleukin-8) is a member of the chemokine family that acts on CXCR1 and CXCR2 receptors. CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, and CXCL7 are also ELR+ chemokine members that bind to these receptors, especially CXCR2. The majority of studies on the biology of CXCL8 and their receptors have been performed in polymorphonuclear leukocytes. However, many other cells express CXCR1/CXCR2, including epithelial, endothelial, fibroblasts and neurons, contributing to the biological effects of CXCL8. There is substantial amount of experimental data suggesting that CXCL8 and receptors contribute to elimination of pathogens, but may also contribute significantly to disease-associated processes, including tissue injury, fibrosis, angiogenesis and tumorigenesis. Here, we discuss the biology of CXCL8 family and the potential therapeutic use of antagonists or blockers of these molecules in the context of organ-specific diseases.
Assuntos
Inflamação/metabolismo , Interleucina-8/metabolismo , Receptores de Interleucina-8A/metabolismo , Receptores de Interleucina-8B/metabolismo , Anticorpos Monoclonais , Anticorpos Monoclonais Humanizados , Benzamidas/uso terapêutico , Ciclobutanos/uso terapêutico , Humanos , Inflamação/prevenção & controle , Interleucina-8/antagonistas & inibidores , Modelos Biológicos , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Receptores de Interleucina-8A/antagonistas & inibidores , Receptores de Interleucina-8B/antagonistas & inibidoresRESUMO
Objetivo : Avaliar o efeito da sibutramina na perda de peso de adolescentes obesos.Sujeitos e métodos : Estudo duplo-cego placebo controlado tipo cross over com duração de 13 meses. Foram incluídos no estudo 73 adolescentes obesos de ambos os sexos com idades entre 10 e 18 anos. A avaliação antropométrica foi realizada a cada 40 dias em média. Os exames laboratoriais e de imagem foram realizados antes, no período de wash-out e ao final dos 13 meses.Resultados : A porcentagem de pacientes que perderam 10% do peso inicial no placebo foi de 46% e, no grupo sibutramina, foi de 75%. Quando usaram o placebo, o peso em média se elevou em 1,61 kg, e o IMC reduziu em média 0,24 kg/m2, enquanto com o uso da sibutramina o peso reduziu em média 4,47 kg e o IMC reduziu em média 2,38 kg/m2 com p < 0,001.Conclusões : A sibutramina induziu significantemente mais perda de peso em adolescentes obesos em comparação ao placebo, sem efeitos colaterais significativos. A curva de evolução ponderal foi diferente de acordo com o momento em que a sibutramina foi introduzida. Esse achado indica que o melhor momento de introdução da sibutramina é quando a adesão começa a falhar. Arq Bras Endocrinol Metab. 2014;58(3):243-50.
Objective : To evaluate the effect of sibutramine on weight loss in obese adolescents.Subjetcs and methods A double-blind controlled study lasting 13 months. The study included 73 obese adolescents of both sexes aged between 10 and 18 years. Laboratory tests and imaging studies were performed before, during wash-out, and at the end of 13 months.Results : The percentage of patients who lost 10% of their initial weight in the placebo group was 46%, and in the sibutramine group was 75%. When placebo was used, average weight rose by 1.61 kg, and BMI decreased by 0.24 kg/m2 whereas with the use of sibutramine, weight decreased by 4.47 kg, and average BMI decreased, 2.38 kg/m2, with p < 0.001.Conclusions : Sibutramine induced significantly more weight loss in obese adolescents compared with placebo, without significant side effects. The weight loss curve was different depending on the moment sibutramine was introduced. This finding indicates that the best time to start sibutramine is when adhesion begins to fail. Arq Bras Endocrinol Metab. 2014;58(3):243-50.
Assuntos
Adolescente , Criança , Feminino , Humanos , Masculino , Depressores do Apetite/uso terapêutico , Ciclobutanos/uso terapêutico , Obesidade Infantil/tratamento farmacológico , Redução de Peso/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Índice de Massa Corporal , Glicemia/análise , Estudos Cross-Over , Colesterol/sangue , Ciclobutanos/efeitos adversos , Método Duplo-Cego , Insulina/sangue , Leptina/sangue , Segurança do Paciente , Obesidade Infantil/sangue , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
CONTEXT: No long-term studies have compared centrally acting drugs for treating obesity. OBJECTIVE: To compare the efficacy and safety of diethylpropion (DEP), fenproporex (FEN), mazindol (MZD), fluoxetine (FXT) and sibutramine (SIB) in promoting weight loss. DESIGN AND SETTING: A prospective, randomized, placebo (PCB)-controlled study conducted at a single academic institution. PATIENTS: A total of 174 obese premenopausal women. INTERVENTION: Participants randomly received DEP 75 mg (n=28), FEN 25 mg (n=29), MZD 2 mg (n=29), SIB 15 mg (n=30), FXT 20 mg (n=29) or PCB (n=29) daily over 52 weeks. Diet and physical activity were encouraged. MAIN OUTCOME MEASURES: The primary endpoints were changes in body weight and the proportion of women who achieved at least 5% weight loss by week 52 in the intent-to-treat population. Other measurements included anthropometry, safety, metabolic and cardiovascular parameters. RESULTS: Weight loss was greater than PCB (-3.1±4.3 kg) with DEP (-10.0±6.4 kg; P<0.001), SIB (-9.5±5.9 kg; P<0.001), FEN (-7.8±6.9 kg; P<0.01) and MZD (-7.4±4.9 kg; P<0.01) but not with FXT (-2.5±4.1 kg). Ten (33.3%) women lost⩾5% of their initial weight with PCB, compared with 20 (71.4%; P<0.001) with DEP, 20 (69%; P<0.02) with FEN, 21 (72.4%; P<0.01) with MZD, 22 (73.3%; P<0.001) with SIB and 10 (35.5%) with FXT. Each medically treated group experienced more adverse events compared with PCB (P<0.001). Compared with PCB, constipation was more prevalent with DEP, SIB and MZD (P<0.01); anxiety was more prevalent with DEP (P=0.01); and irritability occurred more frequently with DEP and FEN (P=0.02). Significant improvements in the depression and anxiety scores, binge-eating episodes and quality of life correlated with weight loss. CONCLUSION: The centrally acting drugs DEP, FEN, MZD and SIB were more effective than PCB in promoting weight loss in obese premenopausal women, with a satisfactory benefit-risk profile.
Assuntos
Anfetaminas/uso terapêutico , Fármacos Antiobesidade/uso terapêutico , Ciclobutanos/uso terapêutico , Dietilpropiona/uso terapêutico , Fluoxetina/uso terapêutico , Mazindol/uso terapêutico , Obesidade/tratamento farmacológico , Redução de Peso/efeitos dos fármacos , Adulto , Índice de Massa Corporal , Brasil , Dieta Redutora , Feminino , Seguimentos , Humanos , Obesidade/prevenção & controle , Estudos Prospectivos , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Because of the increasing prevalence of obesity, prevention and treatment of overweight has become a major public health concern. In addition to diet and exercise, drugs are needed for patients who failed to lose weight with behavioral treatment. The current article aimed to summarize recent concerns on the safety and efficacy of appetite suppressants. Several appetite suppressants have been banned for safety reasons. In 2010, sibutramine was withdrawn from the market because a long-term study showed it increased the risks of cardiovascular events. So far no study with a sufficiently large sample size has demonstrated that appetite suppressants can reduce morbidity and mortality associated with overweight. The withdrawal of sibutramine highlights that guidelines for the evaluation of weight control drugs must be more stringent, and studies on their long-term health benefits are needed prior to their marketing.
O aumento da prevalência da obesidade tornou a prevenção e tratamento do sobrepeso importante desafio para a Saúde Pública. Além da dieta e exercício, os medicamentos são necessários para pacientes que não conseguem perder peso com as mudanças comportamentais. O objetivo do artigo foi sumarizar as preocupações atuais com a segurança e efetividade de medicamentos inibidores do apetite. Vários anorexígenos foram banidos por razões de segurança. Em 2010, a sibutramina foi retirada do mercado porque um estudo de longa duração mostrou que ela aumentava o risco de eventos cardiovasculares. Até agora nenhum estudo com número expressivo de pacientes demonstrou que anorexígenos reduzem a morbi-mortalidade associada ao sobrepeso. A retirada da sibutramina do mercado mostra que diretrizes para avaliação de medicamentos anorexígenos devem ser mais rigorosas, e que estudos de longa duração sobre os benefícios para a saúde devem ser realizados antes da comercialização.
El aumento de la prevalencia de la obesidad ha convertido la prevención y tratamiento del sobrepeso importante desafío para la Salud Pública. Aunado a la dieta y ejercicio, los medicamentos son necesarios para pacientes que no logran perder peso con los cambios de comportamiento. El objetivo del artículo fue englobar las preocupaciones actuales con la seguridad y la efectividad de medicamentos inhibidores del apetito. Varios anorexígenos fueron eliminados por razones de seguridad. En 2010, la sibutramina fue retirada del mercado porque un estudio de larga duración demostró que ésta aumentaba el riesgo de eventos cardiovasculares. Hasta ahora ningún estudio con número considerable de pacientes demostró que anorexígenos reducen la morbi-mortalidad asociada al sobrepeso. La retirada de sibutramina del mercado muestra que directrices para evaluación de medicamentos anorexígenos deben ser más rigurosas, y que estudios de larga duración sobre los beneficios para la salud deben ser realizados antes de la comercialización.
Assuntos
Adulto , Humanos , Fármacos Antiobesidade/uso terapêutico , Depressores do Apetite/uso terapêutico , Ciclobutanos/uso terapêutico , Aprovação de Drogas , Obesidade/prevenção & controle , Fármacos Antiobesidade/efeitos adversos , Depressores do Apetite/efeitos adversos , Doenças Cardiovasculares/etiologia , Ensaios Clínicos como Assunto , Ciclobutanos/efeitos adversos , Obesidade/tratamento farmacológico , Fatores de Risco , Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The World Health Organization reports that waist circumference (WC) independent of weight or body mass index (BMI) predicts cardiovascular risk. We undertook this study to determine the change of prevalence in comorbidities associated with obesity and cardiovascular risk after favorably modifying WC. METHODS: We studied 153 nondiabetic patients with obesity (BMI =30 kg/m²) and WC in women =80 cm and in men =94 cm who entered a weight control program for 2 years. We evaluated the evolution of their anthropometric measurements and metabolic status. Ninety patients (58.8%) completed the study. With the prior acceptance of the patients, they received nutritional advice and psychological and physical activity support during their monthly visits. Also, anthropometric measurements and blood pressure were evaluated. At the beginning and after each 6 months, glucose, total cholesterol, HDL cholesterol and triglycerides were determined. At the beginning and at the end of study the Framingham risks were evaluated. RESULTS: Of the 90 patients, 37 (group 1) decreased their WC: in women <80 cm and in men <94 cm. In 53 patients (group 2) there were no significant changes. Changes were shown in group 1 for blood pressure (from 36.6% to 21.6%), hyperglycemia >100 mg/dl decreased from 18.8% to 8.1%, triglycerides >150 mg/dl decreased from 28.8% to 18.9% and Framingham risk at 10 years decreased. CONCLUSIONS: There is a direct relationship between WC and cardiovascular risk. When WC decreases, cardiovascular risk is favorably modified. Measurement of WC is a good predictor of cardiovascular risk.