A 62-year-old man with type 2 diabetes on glimepiride presents with diaphoresis and confusion. His glucometer reads 48 mg/dL. He recovers after IV dextrose but has two more episodes over the next week. Which property of the sulfonylurea most predisposes him to prolonged hypoglycemia compared to repaglinide?
- A High protein binding causing displacement interactions
- B Renal excretion of unchanged drug causing accumulation
- C Long half-life of the parent drug and active metabolites binding the SUR1 receptor ✓
- D Inhibition of hepatic CYP3A4 leading to auto-inhibition
Correct answer: C. Long half-life of the parent drug and active metabolites binding the SUR1 receptor
Explanation
Sulfonylureas like glimepiride bind the SUR1 subunit of the K-ATP channel on pancreatic beta cells and have long durations with active metabolite secretion, causing prolonged insulin secretion and recurrent hypoglycemia. Repaglinide, a meglitinide, has a short half-life and glucose-dependent clearance, making it less prone to prolonged episodes. The difference is kinetic, not metabolic.
Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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