Actions and Spectrum: 

• The mechanism of action of tolbutamide involves binding to and blocking ATP-sensitive potassium (KATP) channels in the beta cells of the pancreas. This leads to membrane depolarization and calcium influx, which triggers insulin release from the beta cells. 
• tolbutamide has a spectrum of activity that is limited to the treatment of type 2 diabetes. It is not adequate for treating type 1 diabetes or diabetic ketoacidosis, and it is not recommended for use in patients with severe liver or kidney disease.
• The drug is most effective in patients with mild to moderate hyperglycemia. It is often used with lifestyle modifications, such as diet and exercise, to control blood glucose levels. 

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Frequency not defined 

Dermatologic reactions 

Agranulocytosis 

Aplastic anemia 

Heartburn 

Hypoglycemia 

Disulfiram-like reactions 

Hyponatremia 

Thrombocytopenia 

Nausea/vomiting 

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: tolbutamide is contraindicated in patients with known hypersensitivity or allergy to sulfonylurea medications. 
• Type 1 diabetes: tolbutamide is ineffective for treating type 1 diabetes and should not be used in patients with this condition. 
• Diabetic ketoacidosis: tolbutamide is contraindicated in patients with diabetic ketoacidosis, a severe complication of diabetes that can lead to a life-threatening condition. 
• Severe liver or kidney disease: tolbutamide is metabolized in the liver and excreted in the urine. Therefore, it should not be used in patients with severe liver or kidney disease. 
• Pregnancy and lactation: tolbutamide should be used cautiously in pregnant and lactating women due to limited data on its safety in these populations.

Caution: 

• Impaired liver or kidney function: tolbutamide is metabolized in the liver and excreted in the urine. Patients with impaired liver or kidney function may be at increased risk of adverse effects from the medication. 
• Elderly patients: Elderly patients may be more sensitive to the effects of tolbutamide and may require lower doses or more frequent monitoring. 
• Malnourished patients: Malnourished patients may be more susceptible to the effects of tolbutamide and may require lower doses or more frequent monitoring. 
• Alcohol use: Alcohol can potentiate the hypoglycemic effects of tolbutamide and increase the risk of hypoglycemia. 
• Surgery or illness: Patients undergoing surgery or experiencing an acute illness may require adjustments to their tolbutamide dosage or treatment regimen. 
• Pregnancy and lactation: tolbutamide should be used with caution in pregnant and lactating women due to limited data on its safety in these populations 

Pregnancy consideration: C 

Lactation:  

• Excretion of the drug in human breast milk is unknown.  
• tolbutamide should be used with caution in lactating women due to limited data on its safety in these populations 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology: 

• tolbutamide is an oral hypoglycemic medication belonging to the sulfonylurea class of drugs. It works by stimulating insulin release from the beta cells in the pancreas, thereby reducing blood glucose levels in patients with type 2 diabetes. 
• The mechanism of action of tolbutamide involves binding to and blocking ATP-sensitive potassium (KATP) channels in the beta cells of the pancreas. This leads to depolarization of the cell membrane and increased calcium influx, which triggers insulin release from the beta cells. 

Pharmacodynamics: 

• The pharmacodynamics of tolbutamide involves its ability to stimulate insulin secretion from the pancreatic beta cells, reducing blood glucose levels in patients with type 2 diabetes. 
• tolbutamide binds to and blocks ATP-sensitive potassium (KATP) channels in the pancreatic beta cells, depolarizing the cell membrane and increasing calcium influx. This triggers insulin release from the beta cells into the bloodstream, lowering blood glucose levels.

Pharmacokinetics: 

Absorption 

tolbutamide is well-absorbed orally and reaches peak serum levels within 3-4 hours after administration.  

Distribution 

The volume of distribution (Vd) of tolbutamide is 0.15 L/kg, indicating that it is primarily confined to the blood and extracellular fluid.  

Metabolism 

tolbutamide is extensively metabolized in the liver by the hepatic P450 enzyme CYP2C9 to form inactive metabolites such as carboxytolbutamide and hydroxymethyltolbutamide.  

Elimination and Excretion 

tolbutamide is primarily eliminated in the urine, with approximately 70-80% of the drug and its metabolites excreted within 24 hours of administration. The half-life of tolbutamide is relatively short, ranging from 4.5 to 6.5 hours, indicating that it is rapidly eliminated from the body. 

Administration: 

tolbutamide is usually administered orally as a tablet, with dosages ranging from 500 to 2000 mg per day, depending on the patient’s condition and response to treatment. It is usually taken 1-2 times daily, with or after meals, to reduce the risk of hypoglycemia (low blood sugar) 

Patient information leaflet 

Generic Name: tolbutamide 

Pronunciation: [ tole-BYOO-ta-mide ] 

Why do we use tolbutamide? 

• tolbutamide is a medication used to treat type 2 diabetes, a condition in which the body does not produce enough insulin or does not use insulin effectively.  
• It belongs to a class of drugs known as sulfonylureas, which work by stimulating the release of insulin from the pancreas and increasing the body’s sensitivity to insulin