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Novos alvos na farmacoterapia da obesidade
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Abstract(s)
Atualmente, a obesidade é um tema que merece uma atenção acrescida devido ao aumento e da sua prevalência entre a população mundial, nomeadamente entre as crianças, que desde cedo são afetadas por esta patologia correndo graves riscos de desenvolverem futuras comorbilidades.
Esta é uma doença multifatorial que resulta da interação complexa entre fatores genéticos, metabólicos, hormonais, ambientais, comportamentais e culturais. A hiperfagia, o consumo excessivo de lípidos e hidratos de carbono e sedentarismo são os principais fatores implicados na sua fisiopatologia. O método mais utilizado para o diagnóstico da obesidade é o cálculo do Índice de Massa Corporal (IMC). O excesso de peso (IMC de 25 Kg/m2 ou mais) e a obesidade (IMC maior que 30 Kg/m2) são a quinta causa de morte a nível mundial, pelo que é fundamental reunir esforços no sentido de reduzir esta epidemia.
A reduzida eficiência a longo prazo das modificações de estilo de vida isoladamente exige a necessidade de outro tipo de intervenções, seja por meio do uso adjuvantes de uma (farmacoterapia) ou abordagem mais invasiva, a cirurgia. A cirurgia bariátrica, embora até hoje tenha-se mostrado o método mais efetivo de tratamento dessa enfermidade, pode estar associada a dificuldades nutricionais e metabólicas ainda não totalmente esclarecidas. Por outro lado, a disponibilidade de fármacos anti obesidade ainda é muito limitada, por isso é importante perceber toda a história que levou à suspensão de alguns fármacos previamente existentes, por questões de segurança.
A lorcaserina e a combinação de fentermina-topiramato são dois medicamentos aprovados pela Administração Federal de Alimentos e Medicamentos (FDA, do inglês Food and Drug Administration) recentemente, em 2012. O cetilistato, um inibidor das lipases é assumido como fármaco seguro e ainda mais eficaz, em comparação com o orlistato e encontra-se na fase III de ensaios clínicos. Outros fármacos promissores e que estão em ensaios clínicos de fase III são o liraglutido, um análogo do peptídeo semelhante à glicagina 1 (GLP-1, do inglês Glucagon-like peptide-1), que atua através dos mecanismos periféricos, e a associação bupropiona-naltrexona que atua através de um mecanismo central misto, como inibidor da recaptação de dopamina e noradrenalina e como antagonista dos recetores opioides-μ.
Currently, obesity has become an issue due to its increasing worldwide prevalence, particularly among children, who from an early age are affected by this disease with a serious risk of developing future comorbidities. Although there is a genetic predisposition, this is a multifactorial disease that results from the complex interaction between genetic, metabolic, hormonal, environmental, behavioral and cultural factors. Overeating, excessive ingestion of fats and carbohydrates and a sedentary lifestyle are factors involved in its pathophysiology. The most widely used method for the diagnosis of obesity is calculating the Body Mass Index (BMI). Overweight (BMI of 25 kg/m2 or more) and obesity (BMI greater than 30 kg/m2) are the fifth leading cause of death worldwide, so it is essential to join efforts to reduce this epidemic. The reduced efficiency of long-term changes in lifestyle calls for the need of another type of intervention, either through the use of adjuvants (pharmacotherapy) or through a more invase procedure (surgery). Although bariatric surgery as so far proved to be the most effective method for the treatment of this disease, it may be associated with nutritional and metabolic difficulties which are still unclear. Moreover, the availability of anti-obesity drugs is still very limited, so it is important to understand all the history that led to the suspension of some previously existing drugs due to safety issues. Lorcaserin and the combination of phentermine-topiramate, are two drugs recently approved by the Food and Drug Administration (FDA), in 2012. Cetilistat, an inhibitor of lipases is stated to have a high safety profile, compared with orlistat, which is undergoing Phase III clinical trials. Other promising drugs which are in phase III are liraglutide, an analog of glucagon-like peptide-1, acting through peripheral mechanisms, and the association bupropion-naltrexone that operates through a mixed central mechanism, an inhibitor that reuptakes dopamine and noredrenaline and a μ-opioid receptor antagonist.
Currently, obesity has become an issue due to its increasing worldwide prevalence, particularly among children, who from an early age are affected by this disease with a serious risk of developing future comorbidities. Although there is a genetic predisposition, this is a multifactorial disease that results from the complex interaction between genetic, metabolic, hormonal, environmental, behavioral and cultural factors. Overeating, excessive ingestion of fats and carbohydrates and a sedentary lifestyle are factors involved in its pathophysiology. The most widely used method for the diagnosis of obesity is calculating the Body Mass Index (BMI). Overweight (BMI of 25 kg/m2 or more) and obesity (BMI greater than 30 kg/m2) are the fifth leading cause of death worldwide, so it is essential to join efforts to reduce this epidemic. The reduced efficiency of long-term changes in lifestyle calls for the need of another type of intervention, either through the use of adjuvants (pharmacotherapy) or through a more invase procedure (surgery). Although bariatric surgery as so far proved to be the most effective method for the treatment of this disease, it may be associated with nutritional and metabolic difficulties which are still unclear. Moreover, the availability of anti-obesity drugs is still very limited, so it is important to understand all the history that led to the suspension of some previously existing drugs due to safety issues. Lorcaserin and the combination of phentermine-topiramate, are two drugs recently approved by the Food and Drug Administration (FDA), in 2012. Cetilistat, an inhibitor of lipases is stated to have a high safety profile, compared with orlistat, which is undergoing Phase III clinical trials. Other promising drugs which are in phase III are liraglutide, an analog of glucagon-like peptide-1, acting through peripheral mechanisms, and the association bupropion-naltrexone that operates through a mixed central mechanism, an inhibitor that reuptakes dopamine and noredrenaline and a μ-opioid receptor antagonist.
Description
Trabalho Complementar apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Licenciada em Ciências da Nutrição
Keywords
Obesidade Farmacoterapia Perda de peso Novos fármacos Obesity Drug Weight loss New drugs