DIBONIS TABLETS

Indications

• Type 2 diabetes mellitus
• Non-insulin dependent diabetes mellitus (NIDDM)

Dosage

Children: Refer to the BNF for Children for specific dosing guidance.

Adults: Refer to the BNF for specific dosing guidance.

Mechanism of action

Chlorpropamide binds to ATP-sensitive potassium channels on the surface of pancreatic cells, leading to reduced potassium conductance and membrane depolarization. This depolarization results in calcium ion influx through voltage-sensitive calcium channels, which raises intracellular calcium levels and induces insulin secretion through exocytosis. Additionally, chlorpropamide may reduce hepatic glucose output, increase insulin receptor binding, and suppress the release of glucagon and somatostatin.

Pharmacodynamics

As a sulfonylurea, chlorpropamide is effective in lowering blood glucose levels in patients with type 2 diabetes mellitus, particularly in those with some residual functional pancreatic islet cells. Its mechanism includes acute stimulation of insulin release and potential effects on hepatic glucose production and hormone regulation.

Pharmacokinetics

Chlorpropamide is absorbed well from the gastrointestinal tract, with peak plasma concentrations typically occurring within 1 to 2 hours after oral administration. It has a long half-life, allowing for once-daily dosing in many cases. The drug is metabolized in the liver and excreted primarily through the kidneys. Dosage may need to be adjusted in patients with renal impairment due to the risk of accumulation.

Contra-indications

• Diabetes mellitus type I
• Diabetic ketoacidosis
• Severe renal impairment
• Severe liver impairment
• Hypersensitivity to chlorpropamide or other sulfonylureas

Adverse effects

• Hypoglycemia
• Weight gain
• Gastrointestinal disturbances
• Skin reactions (e.g., rash, pruritus)
• Hematological reactions (e.g., leucopenia, thrombocytopenia)
• Cholestatic jaundice
• Allergic reactions

Interactions

• Alcohol may potentiate the hypoglycemic effect
• Certain medications (e.g., sulfonamides, chloramphenicol, and phenylbutazone) can enhance the hypoglycemic effect
• Thiazide diuretics may reduce the effectiveness of chlorpropamide
• Beta-blockers may mask symptoms of hypoglycemia

Precautions

• Use with caution in patients with renal or hepatic impairment
• Monitor blood glucose levels regularly
• Educate patients on recognizing signs of hypoglycemia
• Consider the risk of hypoglycemia in elderly patients or those with poor nutritional status

Pregnancy

Chlorpropamide is not recommended during pregnancy due to potential risks to the fetus. Alternative management strategies for diabetes should be considered.

Breast-feeding

Chlorpropamide is excreted in breast milk; caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place, protected from light. Keep out of reach of children.

Formulations

• Tablets: 100 mg, 250 mg

Mechanism of action

Sulfonylureas such as chlorpropamide bind to ATP-sensitive potassium channels on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin. ...ACTION OF SULFONYLUREAS APPEARS TO BE STIMULATION OF RELEASE OF INSULIN FROM BETA CELLS. ...TO BE EFFECTIVE, PT MUST HAVE SOME FUNCTIONAL ISLET CELLS... /HYPOGLYCEMIC SULFONYLUREAS/ Sulfonylureas cause hypoglycemia by stimulating insulin release from pancreatic beta cells. Their effects in the treatment of diabetes ... are more complex. /Sulfonylureas/ Sulfonylureas are now...thought to act by a number of different mechanisms. 1. ...produce a depolarization of the pancreatic islet beta cell membrane potassium ion permeability. This results in a release of preformed insulin into the circulation and occurs mostly in non-insulin dependent diabetics. 2. ...reduce basal glucose output from the liver... 3. increase insulin receptor binding... 4. ...increasing intracellular levels of AMP... 5. increase insulin secretion by suppressing the release of glucagon and somatostatin from alpha and delta pancreatic cells. /Sulfonylureas/ Sulfonylureas lower blood glucose in NIDDM by directly stimulating the acute release of insulin from functioning beta cells of pancreatic islet tissue by an unknown process that involves a sulfonylurea receptor on the beta cell. Sulfonylureas inhibit the ATP potassium channels on the beta cell membrane and potassium efflux, which results in depolarization and calcium influx, calcium-calmodulin binding, kinase activation, and release of insulin containing granules by exocytosis, an effect similar to that of glucose. Insulin is a hormone that lowers blood glucose and controls the storage and metabolism of carbohydrates, proteins, and fats. Therefore, sulfonylureas are effective only in patients whose pancreata are capable of producing insulin. /Sulfonylurea antidiabetic agents/

Pharmacodynamics

Chlorpropamide, a second-generation sulfonylurea antidiabetic agent, is used with diet to lower blood glucose levels in patients with diabetes mellitus type II. Chlorpropamide is twice as potent as the related second-generation agent glipizide.