II. Background
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Sulfonylureas
- Sulfonylureas were first discovered in 1940's while investigating SulfonamideAntibiotics
- First Generation Sulfonylureas (e.g. Tolbutamide) were developed in the 1960s
- Second Generation Sulfonylureas were available in the 1980s
- Sulfonylureas are also used as herbicides (block specific plant Amino Acid biosynthesis)
-
Meglitinides
- Meglitinide development started in the 1970s and were marketed in the U.S. in the late 1990s
III. Mechanism
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Sulfonylureas
- Sulfonylureas trigger Insulin release from pancreatic beta cells
- Sulfonylureas stimulate Potassium channel closure on pancreatic beta cell surface
- Secretagogues do NOT burn out the beta cells sooner
- Sulfonylureas may also increase tissue Insulin sensitivity
- Sulfonylureas trigger Insulin release from pancreatic beta cells
-
Meglitinides
- Benzoic acid derived from Sulfonylureas
- Directly stimulates pancreatic beta cells (Similar to Sulfonylureas)
- Binds different sites from Sulfonylureas (Sulfonylurea Receptors 1, 1A and 1B)
- Closes ATP sensitive K+ channels
- Results in Insulin secretion
- Effects
- Predominately effects postprandial Glucose
- Faster oral absorption and onset than Sulfonylureas
- Shorter duration of binding and shorter effect than Sulfonylureas
IV. Medications
- First Generation Sulfonylurea (Listed for historical purposes only)
- Second Generation Sulfonylurea (e.g. Glipizide, Glyburide)
- Non-Sulfonylurea Insulin Secretagogues (e.g. Meglitinide, Repaglinide)