利尿药和降担血糖药.ppt

Medicinal chemistry Chapter 10 Diuretics and Synthetic Hypoglycemic Drugs College of Pharmacy, SDUShutao MaEmail:mashutao@sdu.edu.cn Chapter 10 Diuretics and Synthetic Hypoglycemic Drugs Section 1 Hypoglycemic Drugs Section 2 Diuretics Section 1 Hypoglycemic Drugs The classic triad of symptoms in diabetes is polyphagia, polydypsia (thirst), and polyuria (excess urine). All three result directly from excessive serum glucose levels. Type 1 diabetes usually develops in an acute manner, although the destructive autoimmune process may have been underway for some time. Type 2 diabetes has a more insidious, often asymptomatic onset and its presence is usually detected by routine medical examinations. Definitions Type I Diabetes. Insulin-dependent diabetes mellitus (IDDM), this condition occurs when the β-cells of the pancreatic islets of Langerhans are destroyed, probably by an autoimmune process, such that insulin production is deficient. Type 2 Diabetes. Noninsulin-dependent diabetes mellitus (NIDDM) is very frequently associated with obesity in its mainly adult victims. Serum insulin levels are normal or elevated, so in essence this is a disease of insulin resistance. Biochemistry and Pathogenesis of Diabetes Classifications First Generation Sulfonylureas: tolbutamide. Second Generation Sulfonylureas: glibenclamide. Third Generation Sulfonylureas: glimepiride, repaglinide. Biguanides: metformin. α- Glucosidase Inhibitors: Acarbose, Miglitol. Mechanism of Action Sulfonylureas interact with receptors on pancreatic β-cells to block ATP-sensitive potassium channels. This in turn leads to opening of voltage-sensitive calcium channels which produces an influx of calcium; the influx of calcium results in β-cells production of insulin. An additional effect of sulfonylureas is suppression of gluconeogenesis in the liver. Physical-Chemical Properties Sulfonylureas are weak acids due to the marked delocalization of the nitrogen lone electron pair by the sulfo