indication

For use as an adjunct to diet to lower the blood glucose in patients with non-insulin dependent diabetes mellitus (Type II) whose hyperglycemia cannot be satisfactorily controlled by diet alone.

pharmacology

Tolazamide is an oral blood glucose lowering drug of the sulfonylurea class. Tolazamide appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which tolazamide lowers blood glucose during long-term administration has not been clearly established. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonylurea hypoglycemic drugs. Some patients who are initially responsive to oral hypoglycemic drugs, including tolazamide, may become unresponsive or poorly responsive over time. Alternatively, tolazamide may be effective in some patients who have become unresponsive to one or more other sulfonylurea drugs. In addition to its blood glucose lowering actions, tolazamide produces a mild diuresis by enhancement of renal free water clearance.

mechanism of action

Sulfonylureas likely bind to ATP-sensitive potassium-channel receptors 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.

toxicity

Overdosage of sulfonylureas can produce hypoglycemia. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization.

biotransformation

Tolazamide is metabolized to five major metabolites ranging in hypoglycemic activity from 0 to 70%.

absorption

Rapidly and well absorbed from the gastrointestinal tract.

half life

The average biological half-life of the drug is 7 hours.

route of elimination

Tolazamide is metabolized to five major metabolites ranging in hypoglycemic activity from 0% to 70%. They are excreted principally in the urine.

drug interactions

Acebutolol: Acebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.

Acetylsalicylic acid: Acetylsalicylic acid increases the effect of the sulfonylurea, tolazamide.

Amifostine: Additive hypotensive effects may occur. At chemotherapeutic doses of Amifostine, Tolazamide should be withheld for 24 hours prior to Amifostine administration. Use caution at lower doses of Amifostine.

Atenolol: The beta-blocker, atenolol, may decrease symptoms of hypoglycemia.

Bisoprolol: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Carvedilol: The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.

Chloramphenicol: Chloramphenicol may increase the effect of sulfonylurea, tolazamide.

Clofibrate: Clofibrate may increase the effect of sulfonylurea, tolazamide.

Esmolol: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Labetalol: The beta-blocker, labetalol, may decrease symptoms of hypoglycemia.

Metoprolol: The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.

Nadolol: The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.

Oxprenolol: The beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia.

Phenylbutazone: Phenylbutazone increases the effect of the hypoglycemic agent

Pindolol: The beta-blocker, pindolol, may decrease symptoms of hypoglycemia.

Propranolol: The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.

Rifampin: Rifampin may decrease the effect of sulfonylurea, tolazamide.

Rituximab: Additive hypotensive effects may occur. Consider withholding Tolazamide for 12 hours prior to administration of Rituximab.

Somatropin recombinant: Somatropin may antagonize the hypoglycemic effect of Tolazamide. Dose adjustments of Tolazamide may be required.

Timolol: The beta-blocker, timolol, may decrease symptoms of hypoglycemia.