RESUMO
Since Diabetes Control and Complications Trial (DCCT), intensive therapy has been directed at achieving glucose and glycosylated hemoglobin (HbA1c) values as close to normal as possible regarding safety issues. However, hyperglycemia (especially postprandial hyperglycemia) and hypoglicemia continue to be problematic in the management of type 1 diabetes. The objective of associating other drugs to insulin therapy is to achieve better metabolic control lowering postprandial blood glucose levels. Adjunctive therapies can be divided in four categories based on their mechanism of action: enhancement of insulin action (e.g. the biguanides and thiazolidinediones), alteration of gastrointestinal nutrient delivery (e.g. acarbose and amylin) and other targets of action (e.g. pirenzepine, insulin-like growth factor I and glucagon-like peptide-1). Many of these agents have been found to be effective in short-term studies with decreases in HbA1c of 0.5-1%, lowering postprandial blood glucose levels and decreasing daily insulin doses.
Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas/metabolismo , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Tiazolidinedionas/uso terapêutico , Acarbose/metabolismo , Acarbose/uso terapêutico , Amiloide/metabolismo , Amiloide/uso terapêutico , Diabetes Mellitus Tipo 1/metabolismo , Quimioterapia Combinada , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Hipoglicemia/tratamento farmacológico , Incretinas/metabolismo , Incretinas/uso terapêutico , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/uso terapêutico , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Metformina/uso terapêutico , Antagonistas Muscarínicos/metabolismo , Antagonistas Muscarínicos/uso terapêutico , Pirenzepina/metabolismo , Pirenzepina/uso terapêutico , Período Pós-PrandialRESUMO
Desde o Diabetes Control and Complications Trial (DCCT), a terapia insulínica intensiva tem sido direcionada para alcançar valores de glicemia e hemoglobina glicada (HbA1c) tão próximos do normal quanto a segurança permita. Entretanto, a hiperglicemia (especialmente a hiperglicemia pós-prandial) e a hipoglicemia continuam a ser um problema no manejo do diabetes tipo 1. O objetivo de associar outras drogas à terapia insulínica é diminuir a glicemia pós-prandial. A terapia adjunta pode ser dividida em três grupos, conforme seu mecanismo de ação: 1. Aumento da ação da insulina (metformina e tiazolidinedionas); 2. Alteração da liberação de nutrientes no trato gastrintestinal (acarbose e amilina); 3. Outros modos de ação [pirenzepina, fator de crescimento insulina-símile (IGF-1) e peptídeo semelhante ao glucagon 1 (GLP-1). Muitos desses agentes mostraram, em estudos de curto prazo, diminuição de 0,5 por cento a 1 por cento na HbA1c, diminuir a hiperglicemia pós-prandial e as doses diárias de insulina.
Since Diabetes Control and Complications Trial (DCCT), intensive therapy has been directed at achieving glucose and glycosylated hemoglobin (HbA1c) values as close to normal as possible regarding safety issues. However, hyperglycemia (especially postprandial hyperglycemia) and hypoglicemia continue to be problematic in the management of type 1 diabetes. The objective of associating other drugs to insulin therapy is to achieve better metabolic control lowering postprandial blood glucose levels. Adjunctive therapies can be divided in four categories based on their mechanism of action: enhancement of insulin action (e.g. the biguanides and thiazolidinediones), alteration of gastrointestinal nutrient delivery (e.g. acarbose and amylin) and other targets of action (e.g. pirenzepine, insulin-like growth factor I and glucagon-like peptide-1). Many of these agents have been found to be effective in short-term studies with decreases in HbA1c of 0.5-1 percent, lowering postprandial blood glucose levels and decreasing daily insulin doses.
Assuntos
Humanos , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas/metabolismo , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Tiazolidinedionas/uso terapêutico , Acarbose/metabolismo , Acarbose/uso terapêutico , Amiloide/metabolismo , Amiloide/uso terapêutico , Quimioterapia Combinada , Diabetes Mellitus Tipo 1/metabolismo , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Hipoglicemia/tratamento farmacológico , Incretinas/metabolismo , Incretinas/uso terapêutico , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/uso terapêutico , Metformina/uso terapêutico , Antagonistas Muscarínicos/metabolismo , Antagonistas Muscarínicos/uso terapêutico , Período Pós-Prandial , Pirenzepina/metabolismo , Pirenzepina/uso terapêuticoRESUMO
Since the onset of the AIDS epidemic, some 20 million people have died and the estimate is that today close to 40 million are living with type 1 human immunodeficiency virus (HIV)/AIDS. About 14 thousands people are infected worldwide daily with this disease. Still, only a few pharmaceuticals are available for AIDS chemotheraphy. Some pharmaceuticals act against the virus before the entrance of the HIV into the host cells. One of these targets is the glucosidase protein. This class of enzymes has been recently explored because the synthesis of viral glycoproteins depends on the activity of enzymes, such as glucosidase and transferase, for the elaboration of the polysaccharides. In this work we study several glucosidase inhibitors. The DFT method is used to compute atomic charges and the ligand/receptor interaction was simulated with docking software. Analysis of the interactions of the proposed pharmaceutical, a pseudodisaccharide, with the Thermotoga maritima 4-alpha-glucanotransferase in complex with modified acarbose, the scores from docking as well as the graphical superposition of all the ligands, suggest that our molecular designed pseudo-disaccharide may be a potent glucosidase inhibitor.