Acetohexamide

Acetohexamide is an oral blood glucose-lowering drug of the sulfonylurea class, used primarily in the treatment of Type 2 diabetes. It is an older generation sulfonylurea, introduced in the 1960s. Acetohexamide works by increasing the release of insulin from the pancreas, thus lowering blood sugar levels. It is metabolized in the liver and its action may be prolonged in individuals with liver disease, necessitating careful monitoring and dose adjustments.

Mechanism of Action

Acetohexamide acts by stimulating the beta cells of the pancreatic islets of Langerhans to release insulin. It achieves this by closing potassium channels in the beta cell membrane, which leads to cell depolarization, calcium influx, and, ultimately, insulin secretion. This mechanism is similar to other drugs in the sulfonylurea class but differs in its pharmacokinetic profile and duration of action.

Indications

The primary indication for acetohexamide is the management of Type 2 diabetes in patients who cannot achieve blood glucose control through diet and exercise alone. It is often part of a comprehensive diabetes management plan that includes dietary changes, physical activity, and regular blood sugar monitoring.

Contraindications

Acetohexamide is contraindicated in patients with:

• Type 1 diabetes
• Diabetic ketoacidosis
• Known hypersensitivity to sulfonylureas
• Severe renal or hepatic impairment

Side Effects

Common side effects of acetohexamide include:

• Hypoglycemia
• Weight gain
• Nausea
• Dizziness
• Skin rash

Severe hypoglycemia is a significant risk, especially in elderly patients, those with renal or hepatic impairment, or when used in combination with other glucose-lowering medications.

Drug Interactions

Acetohexamide can interact with a number of other medications, potentially increasing the risk of hypoglycemia or reducing the drug's efficacy. These include:

• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Certain antibiotics
• Antifungal agents
• Beta-blockers
• Alcohol

Patients should inform their healthcare provider of all medications they are taking to avoid potential interactions.

Pharmacokinetics

After oral administration, acetohexamide is rapidly absorbed from the gastrointestinal tract. It is extensively metabolized in the liver to its active metabolites. The elimination half-life of acetohexamide varies, but it is generally between 5 to 8 hours, which may be prolonged in patients with hepatic impairment.

Dosage and Administration

The dosage of acetohexamide is individualized based on the patient's blood glucose response. It is typically initiated at a low dose, with gradual adjustments to achieve optimal glycemic control. Regular monitoring of blood glucose and hemoglobin A1c levels is recommended to assess efficacy and safety.

Conclusion

Acetohexamide is a sulfonylurea drug used in the management of Type 2 diabetes. While effective in lowering blood glucose levels, it requires careful monitoring for side effects, particularly hypoglycemia. As newer generations of diabetes medications become available, the use of acetohexamide has declined, but it remains an option for certain patients under the guidance of a healthcare provider.

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