Diabetes Drugs- Sulphonylureas

Question 1

Sulphonylureas - Pharmacology (2)

Answer 1

1st Generation – Tolbutamide, Chlorpropamide limited use now

2nd Generation – Gliclazide, Glipizide, Glimepiride,
Glibenclamide

Question 2

how do sulphonylureas work?

Answer 2

inhibit ATP sensitive channel

promoting insulin release

Question 3

Sulphonylureas –glucose (5)

Answer 3

Glucose stimulated insulin secretion

1.Glucose metabolism
2.Rise in intracellular ATP from glycolysis and mitochondrial metabolism
3.Closure of ATP sensitive K channel (KATP)
4.Rise in membrane potential triggers Voltage gated Calcium channel
5.Calcium influx leads to insulin exocytosis

Question 4

Sulphonylureas (4)

Answer 4

1. SU binds to SUR1
   2.Closure of ATP sensitive K channel (KATP)
   3.Rise in membrane potential triggers Voltage gated Calcium channel
   4.Calcium influx leads to insulin exocytosis

Question 5

Sulphonylureas - simply (3)

Answer 5

Act directly on pancreatic beta-cells to increase insulin secretion – as such are termed “Insulin secretagogues”

Are glucose independent i.e. insulin secretion even when not needed (when glucose is low or normal).

This results in HYPOGLYCAEMIA.

Question 6

Sulphonylureas – clinical use (5)

Answer 6

Potent glucose lowering. HbA1c ~18 mmol/mol

Increase weight – by 1-2 kg on average

Risk of hypoglycaemia

Most common sulphonylurea in UK = Gliclazide.

Start at 40-80mg od; little benefit by increasing over 80mg bd although max dose 160mg bd.

Question 7

Sulphonylurea side effects

Answer 7

Hypoglycaemia

Weight gain