利尿药和降血糖药 PPT课件.ppt

Medicinal chemistry
Chapter 10 Diuretics and Synthetic Hypoglycemic Drugs
College of Pharmacy, SDUShutao MaEmail:******@sdu.
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 sulfonyl