indication

Used in the management of diabetes mellitus type 2 (adult-onset).

pharmacology

Acetohexamide is an intermediate-acting, first-generation oral sulfonylurea. It lowers blood sugar by stimulating the pancreatic beta cells to secrete insulin and by helping the body use insulin efficiently. The pancreas must produce insulin for this medication to work. Acetohexamide has one-third the potency of chlorpropamide, and twice the potency of tolbutamide; however, similar hypoglycemic efficacy occurs with equipotent dosage of sulfonylureas.

mechanism of action

Sulfonylureas such as acetohexamide bind to an ATP-dependent K⁺ channel on the cell membrane of pancreatic beta cells. This inhibits a tonic, hyperpolarizing outflux of potassium, which causes the electric potential over the membrane to become more positive. This depolarization opens voltage-gated Ca²⁺ channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin.

toxicity

Oral, rat LD₅₀: 5 gm/kg; Oral, mouse LD₅₀: >2500 mg/kg. Symptoms of an acetohexamide overdose include hunger, nausea, anxiety, cold sweats, weakness, drowsiness, unconsciousness, and coma.

biotransformation

Extensively metabolized in the liver to the active metabolite hydroxyhexamide, which exhibits greater hypoglycemic potency than acetohexamide. Hydroxyhexamide is believed to be responsible for prolonged hypoglycemic effects.

absorption

Rapidly absorbed from the GI tract.

half life

Elimination half-life of the parent compound is 1.3 hours and the elimination half-life of the active metabolite is approximately 5-6 hours.

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 sulfonylurea, acetohexamide.

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

Betaxolol: The beta-blocker, betaxolol, may decrease symptoms of hypoglycemia.

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

Carteolol: The beta-blocker, carteolol, may decrease symptoms of hypoglycemia.

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

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

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

Dicumarol: Dicumarol may increase the effect of sulfonylurea, acetohexamide.

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 may increase the effect of acetohexamide.

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

Practolol: The beta-blocker, practolol, may decrease symptoms of hypoglycemia.

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

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

Sotalol: The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.

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