chlorpropamide

Chlorpropamide is an oral blood sugar-lowering drug in a class of medications for diabetes treatment called sulfonylureas. It is one of the first four sulfonylureas to be used to manage type II diabetes and it is commonly referred to as a first generation sulfonylurea. The second generation sulfonylureas are glipizide (Glucotrol, Glucotrol XL), glyburide (Micronase), and glimepiride (Amaryl).

The primary difference between the first and second generation sulfonylureas is in the way they are eliminated from the body. As a result, second generation sulfonylureas usually are taken less frequently each day than first generation sulfonylureas and generally are preferred when there is poor function of the kidneys. The second generation sulfonylureas were first used in the United States in 1984. The FDA approved chlorpropamide in October 1958.

All sulfonylureas lower blood sugar (glucose) by increasing the release of insulin from the pancreas. (Insulin is the hormone that lowers the blood sugar level.)

Approximately 90% of patients with diabetes have type II diabetes, formerly called non-insulin-dependent diabetes mellitus. Type II diabetes usually occurs in adults and is associated with obesity and a strong family history of diabetes. The inability to control blood glucose in type II diabetes is caused by reduced insulin release by the pancreas as well as decreased removal of glucose from the blood by the body's cells.

Chlorpropamide has similar side effects as other sulfonylureas.

The most common side effects of sulfonylureas are:

• Nausea
• Vomiting
• Heartburn
• Diarrhea
• Headache

The above symptoms usually are avoided if the drug is ingested with a meal.

Hypoglycemia may occur during sulfonylurea therapy. Symptoms and signs include:

• hunger,
• nausea,
•  tiredness,
• perspiration,
• headache,
• heart palpitations,
• numbness around the mouth,
• tingling of the fingers,
• tremors,
• muscle weakness,
• blurred vision,
• sensation of cold,
• excessive yawning,
• irritability,
• confusion, or
• loss of consciousness.

All sulfonylureas can lower blood sugar (glucose levels) to the point of causing symptoms and signs (hypoglycemia). Therefore, these agents must be used carefully with patients who have other physical or medical factors that may lower their blood glucose. These factors include:

• kidney or liver disease,
• poor food intake,
• alcohol use, or
• participation in heavy exercise.

Sulfonylureas may cause:

• weight gain,
• sun sensitivity (skin rash), and
• allergic-type skin-reactions such as itching and hives..

Rarely, blood disorders occur; for example, low white cell counts or low red cell counts.

Fluid retention and swelling of the body due to jaundice, hepatitis, or a low blood sodium concentrate occur rarely.

• The recommended dose for middle-aged stable diabetic patients is 250 mg daily. The dose may be increased or decreased by 50 to 125 mg daily at 3 to 5 day intervals.
• Older patients are started at 100 to 125 mg daily. The usual dose maintenance dose is 100 to 500 mg daily.
• Chlorpropamide should be taken 30 minutes before meals.

Drugs that may interact with chlorpropamide and increase the risk of hypoglycemia include:

• Blood thinning agents warfarin (Coumadin, Jantoven)
• chloramphenicol (Ak-Chlor)
• clofibrate (Atromid)
• Alcohol
• MAO inhibitors including tranylcypromine (Parnate)
• Nonsteroidal anti-inflammatory drugs including ibuprofen (Motrin), and aspirin
• Sulfonamides including sulfamethoxazole (Gantanol), phenylbutazone (Azolid), and drugs that make urine more acidic including ammonium chloride.

Diuretics including hydrochlorothiazide (Hydrodiuril) and furosemide (Lasix) may increase blood glucose, reducing the effect of chlorpropamide.

Alcohol may interact with chlorpropamide, to cause moderate to severe facial flushing (increased flow of blood to the face) and an increase in facial temperature.

Beta-blockers may lower or increase glucose levels when used alone. When used with sulfonylureas, beta-blocking drugs may interfere with glucose lowering by the sulfonylureas. In addition, beta-blockers can blunt some of the body's protective responses to hypoglycemia, for example, increased heart rate, thus making it difficult for patients to recognize hypoglycemia. This notwithstanding, beta-blockers have been used successfully in diabetic patients and have been associated with improved survival in diabetics with high blood pressure.

Very high doses of first generation sulfonylureas have been harmful to fetuses in animal studies. No adequate safety and efficacy studies have been conducted in humans. Therefore, sulfonylureas generally are not a good choice for pregnant women.

Chlorpropamide is excreted in breast milk. Because hypoglycemia may occur in the infant who breastfeeds from a mother taking chlorpropamide, either formula feedings or discontinuation of chlorpropamide is strongly recommended in females who are nursing.

What preparations of chlorpropamide are available?

Tablets: 100 or 250 mg

How should I keep chlorpropamide stored?

Chlorpropamide should be stored at room temperature, 15 C to 30 C (59 F to 86 F) in an air-tight container.