The first-generation sulfonylurea drug chlorpropamide has a…
The first-generation sulfonylurea drug chlorpropamide has a half-life of 25-60 hours and a duration of glycaemic effect of 24-72 h. The structurally related analogue, tolbutamide, has a much shorter duration of action, around 6-24 h. a. With reference to the structures of the two compounds, and drug metabolism, suggest why chlorpropamide displays longer-lasting effects than tolbutamide. (3 marks) b. Clinical signs of hypoglycaemia developed in a 3-year-old boy 24 hours after he had mistakenly eaten some of the pretty blue-coloured chlorpropamide tablets, thinking they were sweets. Given that chlorpropamide is an acidic drug with a pKa of ~5.2, suggest an approach to treat the patient through enhanced elimination of the drug, with rationale. (2 marks)