A 55-year-old type 2 diabetic patient on glibenclamide develops severe hypoglycaemia. Compared to glipizide, glibenclamide causes more prolonged hypoglycaemia because:
- A It has active metabolites and is partially renally excreted, accumulating in renal impairment ✓
- B It has a higher intrinsic potency at the SUR1 sulphonylurea receptor
- C It binds irreversibly to pancreatic beta-cell ATP-sensitive K+ channels
- D It undergoes extensive hepatic first-pass metabolism forming pro-drug
Correct answer: A. It has active metabolites and is partially renally excreted, accumulating in renal impairment
Explanation
Glibenclamide (glyburide) is metabolised to weakly active hydroxylated metabolites that are eliminated renally; in elderly patients and those with renal impairment, accumulation causes prolonged hypoglycaemia. Glipizide is metabolised to truly inactive metabolites, making it safer in renal impairment. Both drugs bind to SUR1 reversibly; binding affinity differences do not explain prolonged hypoglycaemia as directly as metabolite accumulation.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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