Advantages And Disadvantages Of Sulfonylureas

TREATMENT

ORAL HYPOGL YCAEMIC AGENTS

Oral hypoglycaemic agents lower blood glucose levels and are effective orally. Due to the chief drawback of insulin that it must be given by injection, oral hypoglycaemic agents came into existence. In 1940s sulfonamides was introduced , but it had hypoglycaemia as the chief side effect. After this, the first clinically acceptable sulfonylurea tolbutamide was introduced in 1957. In 1970s 'second generation' sulfonylureas have been developed which were more potent than the former agents. Clinically useful biguanide phenformin was developed parallel to sulfonylureas in 1957. Recently 3 newer classes of drugs, viz. alpha glucosidase inhibitors, meglitinide analogues, thiazolidinediones and DPP4 inhibitors

Sulfonylureas bind to a specific sulfonylurea receptor (SUR) on pancreatic β cells. Binding decreases an adenosine triphosphate–dependent potassium ion (K+) channel, leading to decreased potassium efflux and subsequent depolarization of the membrane. Voltage-dependent calcium ion (Ca+2) channels open and allow an inward flux of Ca+2. Increases in intracellular Ca+2 cause translocation of secretory granules of insulin to the cell surface and resultant exocytosis of the granule of insulin. Elevated secretion of insulin from the pancreas travels via the portal vein and subsequently suppresses hepatic glucose production. 34

Sulphonylureas are an effective second line therapy for lowering blood glucose. If glycaemia is inadequately controlled by metformin alone, then sulphonylureas are used as an add-on to metformin. Adverse effects of sulphonylureas includes weight gain and hypoglycaemia. The weight gain is not ideal in patients with diabetes who are already overweight or obese, although sulphonylureas are effective treatments in this group. Hypoglycaemia occurs because the closure of KATP channels brings about unregulated insulin secretion, even with normal or low blood glucose