Name: Chlorpropramide (Diabinese)
Class: Anti-Diabetes Agent (Oral Hypoglycemic) (Sulfonylurea) (First Generation)
Mechanism: Interferes w/ATP-sensitive K+ channel. Reduced K+ conductance ® depolarization & influx of Ca2+. Stim. of insulin release from pancreas, ¯ glucagon, binding of insulin to target tissue receptors.
Absorption: Oral.
Dist.: Largely bound to plasma proteins.
Metabolism.: Hepatic.
Excretion, t½: Long duration of action (36+ hr).
Toxicity/S.E.s: Severe side effects in 2-4%. Only 10% still use them after 6-9 yrs of treatment. Sustained hypoglycemia (esp. likely) up to 4-5 days after discont. use. Rash (rare), GI upset (3-4%), hematological disturbance—usu. leukopenia (1%), inappropriate ADH release (® hyponatremia), flushing, disulfiram action (highest incidence of the class), variability in steady state conc. C/i in the elderly. Drug interactions—protein binding (alcohol, b blockers, MAO inhibitors).
Utility: NIDDM—prevents acute hyperglycemic problems, may postpone development of glucose intolerance, may delay thickening of capillary BM.
Special Features: Highest incidence of S.E.’s in sulfonylurea group.