First generation sulfonylureas are the first oral hypoglycemics developed. However, they are rarely used and have been replaced by second generation sulfonylureas based on fewer drug-drug interactions and increased potency. Sulfonylureas can also be used in combination with other oral hypoglycemic drugs in patients who fail initial therapy with lifestyle intervention and metformin. Use caution to avoid severe hypoglycemia. Important to note that sulfonylureas generally are not used in combination with insulin.
First generation sulfonylureas stimulate the pancreatic islet cells to release insulin. These medications bind to ATP-sensitive potassium channels and cause depolarization of the cell membrane. Calcium enters the cells while insulin is released into the bloodstream.
First generation sulfonylureas stimulate insulin release and are indicated for patients with type 2 diabetes with the ability to produce insulin. These drugs are ineffective in patients with type 1 diabetes, since they are unable to produce insulin. Medications such as chlorpropramide and tolbutamide may be used alone or in conjunction with other drug therapy. However, these drugs should be used along with proper diet and exercise for glucose management in patients with type 2 diabetes.
First generation sulfonylureas increase insulin release and may cause hypoglycemia. Since these drugs are metabolized in the liver and excreted by the kidneys, dysfunction in either organs may cause drug toxicity and fatal hypoglycemia. Refer to Picmonic "Hypoglycemia Assessment" for more information.
Several research studies have linked tolbutamide, the first sulfonylurea medication available, with increased risk of cardiovascular toxicity, i.e., sudden cardiac death. Inform patients about the increased risk of adverse cardiovascular reactions.
Instruct the patient to avoid beta blockers due to their suppression of insulin release. Beta blockers may also decrease the symptoms of decreasing blood glucose, primarily tachycardia, and cause severe hypoglycemia.
First generation sulfonylureas are teratogenics and should be avoided during pregnancy. Newborn exposure to sulfonylureas at the time of delivery can result in severe hypoglycemia lasting up to 10 days. Nursing mothers should not take sulfonylureas, since these drugs are excreted into the breast milk and cause hypoglycemia in the infant. Insulin should be substituted for glucose control.
Warn the patient to avoid alcohol while taking first generation sulfonylureas. The combination of these two substances may cause a disulfiram-like reaction manifesting with flushing, palpitations, and nausea. Alcohol potentiates the hypoglycemic effects of the sulfonylurea medications. The reaction may be more of a nuisance than of any significant clinical importance. Be sure to warn patients of the potential for developing this reaction as it may cause embarrassment or anxiety.
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