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Chlorpropamide and Tolbutamide (Orinase) (1st Generation Sulfonylureas)

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Chlorpropamide and tolbutamide are first generation sulfonylureas that promote insulin release. This action increases the amount of circulating insulin to maintain normal blood glucose levels in the body. These drugs are indicated for patients with type 2 diabetes who have the ability to produce insulin (refer to Picmonic "Insulin"). However, first generation sulfonylureas are rarely used due to their lower potency and significant drug-drug interactions. Side effects of these medications include hypoglycemia and cardiovascular toxicity. These drugs should not be used while pregnant, breastfeeding, consuming alcohol, or taking beta blockers.
8 KEY FACTS
MECHANISMS
1st Generation Sulfonylureas
(1) Wand Sulfur-funnel-U-rainbow

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 However, they are rarely used and have been replaced by second generation sulfonylureas based on fewer drug-drug interactions and increased potency.

Stimulate Release of Insulin
Releasing Insect-syringes

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.

INDICATIONS
Type 2 Diabetes
Dyed-bead-pancreas in (2) Tutu

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.

SIDE EFFECTS
Hypoglycemia
Hippo-glue-bottle

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.

Possible Cardiovascular Toxicity
Heart with Vessels and Toxic-green-glow

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.

CONSIDERATIONS
Beta-blockers Reduce Effects
Beta-fish with Blocks and Down-arrow Effects

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.

Avoid During Pregnancy and Breast Feeding
Avoid-sign Pregnant-woman Breast-feeding

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.

Avoid Alcohol
Avoid-sign Alcoholic-martini

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. 

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