during glucose metabolism. Sulfonylureas are chemically related to sulfon-
amides but lack antibacterial activity.
Sulfonylureas are classified as first- and second-generation drugs and each
generation is divided into short-acting, intermediate-acting, and long-acting
antidiabetics.
First-generation sulfonylureas are:- Tolbutamide (Orinase)
- Acetohexamide (Dymelor)
- Tolazamide (Tolinase)
- Chlorpropamide (Diabinese)
Second-generation sulfonylureas include- Glipizide (Glucotrol)
- Glyburide nonmicronized (DiaBeta, Micronase)
- Glimepiride (Amryl)
Second-generation sulfonylureas increase tissue response to insulin and
decrease glucose production by the liver. This results in greater hypoglycemic
potency at smaller doses. Second-generation sulfonylureas have a longer dura-
tion of action and cause few side effects, but should not be used if the patient has
liver or kidney dysfunction.
Nonsulfonylureas are new drugs that affect the hepatic and GI production of
glucose. For example, metformin (Glucophage) is a nonsulfonylurea biguanide
compound that acts by decreasing hepatic production of glucose from stored
glycogen. The result is a reduced increase in serum glucose following a meal and
limits the degree of post-prandial (after a meal) hyperglycemia.
Metformin (Glucophage) also decreases the absorption of glucose from the
small intestine and may increase insulin receptor sensitivity as well as peripheral
glucose uptake at the cellular level. Metformin does not produce hypoglycemia
or hyperglycemia and can cause GI disturbances. Metformin can be used alone.
When combined with a sulfonylurea, however, it is useful in cases resistant to
oral antidiabetics.
Alpha-glucosidase inhibitors (acarbose [Precose]) inhibit alpha glucosidase,
the digestive enzyme in the small intestine that is responsible for the release of
glucose from the complex carbohydrates in the diet. By inhibiting alpha glu-
cosidase, carbohydrates cannot be absorbed and instead, pass into the large
intestine. Acarbose has no systemic effects, is not absorbed into the body in sig-
nificant amounts, and does not cause a hypoglycemic reaction.
CHAPTER 21 Endocrine Medications^395