Tolbutamide, also known as D860, comes in tablet form, with each tablet containing 500mg. The maximum daily dosage ranges from 2000 to 3000mg, taken in 2 to 3 divided doses 30 minutes before meals. It is excreted by the kidneys at a rate of 100%, with a moderate risk of hypoglycemia (++). Its characteristics include a mild effect, affordability, making it suitable for rural patients. However, it can cause hypoglycemic reactions and increase the renal burden, thus it is not recommended for the elderly and those with renal dysfunction. Tolbutamide lowers blood sugar levels in both healthy individuals and diabetic patients, but is ineffective in those who have lost pancreatic function.
Structural Features:
It is one of the earliest sulfonylurea insulin secretagogues.
Indications:
An antidiabetic medication, suitable for stable, mild to moderate adult diabetes patients.
Typical Adverse Reactions:
1.Tolbutamide has a gentle effect and rarely causes hypoglycemia. However, due to its metabolism through the liver and kidneys, patients with liver and kidney dysfunction may experience hypoglycemia, manifesting as hunger, palpitations, sweating, trembling, and fatigue. Immediate discontinuation of the drug, consumption of food or sugary water is advised in such cases, with severe instances requiring intravenous glucose.
2.Gastrointestinal reactions: Common symptoms include lack of appetite, burning sensation in the upper abdomen, nausea, and diarrhea. Taking the medication after meals, starting with a small dose, and adding antacids can alleviate symptoms.
3.Allergic reactions: Rare occurrences of rash and fever.
4.Decrease in blood cells: Rare cases of leukopenia, granulocytopenia, and thrombocytopenia, which require discontinuation of the drug and symptomatic treatment.
Contraindications:
- Type I diabetes patients;
- Type II diabetes patients with ketosis, acidosis, coma, severe burns, infections, trauma, and major surgery under stress conditions;
- Patients with liver and kidney dysfunction;
- Those allergic to sulfa drugs;
- Patients with leukopenia.
Pharmacological Effects of Tolbutamide Tablets:
- Selectively acts on pancreatic β-cells to stimulate the secretion of insulin, lowering blood sugar.
- Enhances the hypoglycemic effect of exogenous insulin, and in large doses, can reduce the binding of insulin to plasma proteins and inhibit its metabolism.
- Acts on target organs to improve the sensitivity of target cells to insulin and increases the number of insulin receptors on cell membranes, enhancing the post-receptor effect of insulin and exerting a hypoglycemic effect.
- Inhibits the secretion of glucagon, enhancing the effect of insulin.
Drug Interactions:
- Tolbutamide can enhance the toxicity of ethanol; alcohol consumption should be avoided during treatment. Concurrent use with alcohol can cause abdominal cramps, nausea, vomiting, headache, facial flushing, and hypoglycemia.
- When used with β-blockers, the risk of hypoglycemia can increase, and symptoms of hypoglycemia such as increased pulse rate and hypertension can be masked. The use of selective β-blockers like atenolol and metoprolol in small amounts is less likely to cause this issue.
- Chloramphenicol, guanethidine, insulin, monoamine oxidase inhibitors, cortisone, hydrocortisone, bumetanide, salicylates, sulfonamides used concurrently with tolbutamide can enhance the hypoglycemic effect.
- Corticosteroids, adrenaline, phenytoin, thiazide diuretics, thyroid hormones can increase blood sugar levels; the dosage of tolbutamide may need to be increased when used concurrently.
Precautions:
Regular monitoring of blood glucose, urine glucose, ketone bodies, urine protein, liver and kidney function, and eye examinations should be conducted during treatment.
Dosage and Administration:
- Oral: The usual dose is 0.5g once, 1-2g per day. Initially, 0.5g is taken before breakfast or before breakfast and lunch, or 0.25g three times a day, half an hour before meals, gradually increasing the dose according to medical needs, generally up to 1.5g per day, with a maximum of 3g per day.
- Intravenous injection of 1g of tolbutamide sodium salt (dissolved in 20ml of saline) results in a decrease in blood sugar within 2 minutes, lasting about 3 hours. This reaction is specific and can be used for diagnosis, but hypoglycemia should be prevented.
Manufacturers in the United States: Pfizer, Mylan, Teva Pharmaceuticals, Sandoz, Apotex.