DRUGS TO TREAT HYPERGLYCEMIA

Drugs that primarily stimulate insulin secretion by binding to the sulfonylurea receptor on the beta cells A)Sulfonylureas Stimulate insulin release from pancreatic B cells. Specific receptors on the surface of pancreatic B cells bind to sulfonylureas. Activation of these receptors closes potassium channel resulting in depolarization of the B cells This depolarized state permits calcium to enter the cell and actively promotr insulin release Not indicated to use in type 1 DM since require pancretic B cells

MEGLITINIDE ANALOG-Repaglinide
o Bind to sulfonylurea receptor and closing the ATP-sensitive potassium channel. o Plasma half life less than 1 hour. o Side effect:Hypoglycemia, weight gain o Useful in patient with renal impairment/elderly

2)Drugs that alter insulin action

A) Metformin Primary action is on liver ,reducing hepatic gluconeogenesis by activating adenosine monophasphate-activated protein kinase (AMPK). AMPK act as intracellular energy sensor andhas roleregulating gluconeogenesis Half life:1.5-3 hours,not bound with plasma protein,excreted unchanged by kidney. Used as adjunct to diet (obese),improve both fasting and postprandial hyperglycemia and hypertriglyceridemia without weight gain. Side effect: gastointestinal symptom

Thiazolidinediones
They bind avidly to peroxisome proliferatoractivated receptor gamma in adipocytes to promote adipogenesis and fatty acid uptake (in peripheral but not visceral fat). By reducing circulating fatty acid concentrations and lipid availability in liver and muscle, the drugs improve the patients sensitivity to insulin. Thiazolidinediones favourably alter concentrations of the hormones secreted by adipocytes, particularly adiponectin. They increase total body fat and have mixed effects on circulating lipids.

3) Drugs that affect absorption of glucose

ACARBOSE
Alpha-glucosidase inhibitors are saccharides that act as competitive inhibitors of enzymes needed to digest carbohydrates: specifically alpha-glucosidase enzymes in the brush border of the small intestines. The membrane-bound intestinal alphaglucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the small intestine. Acarbose also blocks pancreatic alpha-amylase in addition to inhibiting membrane-bound alpha-glucosidases. Pancreatic alphaamylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine.

 Inhibition of these enzyme systems reduces the rate of digestion of carbohydrates. Less glucose is absorbed because the carbohydrates are not broken down into glucose molecules. In diabetic patients, the short-term effect of these drugs therapies is to decrease current blood glucose levels: the long term effect is a small reduction in hemoglobin A1c level