Name: Glipizide (Glucotrol)
Class: Anti-Diabetes Agent (Oral Hypoglycemic) (Sulfonylurea) (Second Gen.)
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.
Excret., t½: Intermed. duration of action (t½=1.5-5 hr), but duration of effect 18 hr.
Toxicity/S.E.s: Severe side effects in 2-4%. Only 10% still use them after 6-9 yrs of treatment. Sustained hypoglycemia up to 4-5 days after discontinued use. Rash (rare), GI upset (3-4%), hematological disturbance—usu. leukopenia (1%), inappropriate ADH release (® hyponatremia), flushing, disulfiram action, variability in steady state conc. Drug interactions—protein binding (alcohol, b blockers, MAO inhibitors)l.
Utility: NIDDM—prevents acute hyperglycemic problems, may postpone development of glucose intolerance, may delay thickening of capillary BM.
Special Features: More lipophilic and 100x more potent than first gen.