Hassan Mohammad AlShehri ID#2051040006
Oral Hypoglycemic AgentsSULFONYLUREAS
Accidentally discovered following the observation that sulfa antibiotics(sulfonamides) caused hypoglycemia in experimental animalsThey are divided into two groups or generations of agents.Structural Formulas of the SulfonylureasFirst Generation:Tolbutamide, Tolazamide, Acetohexamide
Glyburide, Glipizide, GliclazideSecond genertion are non-polar and minimally bound to albumin which reducesincidence of certain types of drug interaction seen with first generationsulfonylureas.Mechanism of Sulfonylurea Actiona. Stimulate the release of insulin from pancreatic
cells.Sulfonylureas bind to SUR and block ATP-dependent K
channels- This reduces K
efflux leading to:
cell depolarization, calcium influx and secretion of insulin.b. May also increase the sensitivity of peripheral tissues to insulin.Therapeutic Uses of SulfonylureasOf value only in the management of type 2 diabetic patients that have notdemonstrated ketosis and have not responded adequately to dietary therapy andweight control."
patient must have functional beta cells
"Side Effects of Sulfonylureas1. May cause hypoglycemia2. Weight gain, allergic reactions, pruritus, rash, hepatotoxicity, andphotosensitivity are possible3. Hyponatremia and water retention - non
cell effects4.Therapeutic effect may be antagonized by thiazide diuretics, estrogens or anyagents that inhibit insulin release or antagonize peripheral action.
Repaglinide (Prandin®/NovoNorm®)- an insulinotropic agent: stimulates insulin secretion by pancreatic beta cells-fast acting - short duration, administered before meals - from 30 min prior, rightup to meal time - unlike sulfonylureas (30 min)