Makindo Medical Notes

💊 Tolbutamide is a short-acting sulfonylurea used in the management of type 2 diabetes mellitus (T2DM). It lowers blood glucose by stimulating pancreatic insulin secretion but carries a risk of hypoglycaemia, especially in elderly or renally impaired patients. Its short half-life makes it safer than longer-acting agents (e.g. glibenclamide) in older adults.

📘 About

• Always check the BNF entry for latest dosing, interactions, and cautions.
• First-generation sulfonylurea — shorter acting than chlorpropamide or glibenclamide.
• Now largely replaced by newer agents (e.g. gliclazide) but still useful for short-term glycaemic control or diagnostic testing.

⚙️ Mode of Action

• Stimulates insulin release by binding to the sulfonylurea receptor (SUR1) on pancreatic β-cells → closes K_ATP channels → depolarisation → calcium influx → insulin exocytosis.
• Also reduces hepatic gluconeogenesis and increases peripheral glucose uptake.
• Requires functioning β-cells → not effective in type 1 diabetes.

💊 Indications

• Type 2 diabetes mellitus inadequately controlled by diet and lifestyle measures alone.
• Sometimes used in diagnostic testing for insulin secretion (in endocrinology settings).

💉 Dose

• T2DM: 0.5–1.5 g daily in divided doses with meals (max 2 g/day).
• Start low and titrate gradually based on blood glucose response.
• Avoid skipping meals — risk of hypoglycaemia.

🔄 Interactions

• Increased hypoglycaemia risk with: chloramphenicol, sulfonamides, co-trimoxazole, warfarin, fibrates, NSAIDs.
• Reduced effect with corticosteroids, thiazides, or phenytoin.
• Alcohol may enhance hypoglycaemia and cause flushing reaction.

⚠️ Cautions

• Use cautiously in renal or hepatic impairment — slower clearance increases toxicity risk.
• In obese patients, sulfonylureas may promote weight gain — combine or switch to metformin for better metabolic outcomes.
• Stop and consider variable-rate insulin infusion (VRIII) during acute illness or perioperatively.

🚫 Contraindications

• Type 1 diabetes, diabetic ketoacidosis (DKA).
• Severe hepatic or renal impairment.
• Known hypersensitivity to sulfonylureas or sulfonamides.

💥 Adverse Effects

• 💧 Hypoglycaemia — main risk; can cause confusion, sweating, and collapse.
• ⚖️ Weight gain due to increased insulin levels.
• GI upset, nausea, rash, or photosensitivity.
• Rare: hepatotoxicity, cholestatic jaundice, and blood dyscrasias (e.g. agranulocytosis).

🧠 Teaching Note

Tolbutamide illustrates the core mechanism of sulfonylureas: K_ATP channel blockade → insulin release. Its short half-life (4–8 hours) makes it a safer prototype for elderly or renally compromised patients. Always educate patients on recognising and treating hypoglycaemia — a key safety issue for all insulin secretagogues.

📚 References

• BNF: Tolbutamide
• NICE NG17: Type 2 Diabetes in Adults (2024)
• UKCPA Handbook of Perioperative Medicines