DRUGS AND THEIR TARGETS IN T2DM - JP

Question 1

Describe the steps in insulin secretion

Answer 1

1. Increase in Blood Glucose
2. Glucose enters pancreatic beta cells via GLUT-2 transporter.
3. Glucose gets phosphorylated to Glucose-6-Kinase by Glucokinase
4. Glycolysis of Gluco-6-Kinase yields ATP.
5. Katp channels close causing membrane DEPOLARISATION.
6. Depolarisation causes Ca2+ channels to open and Ca2+ to enter the cell triggering insulin secretion.

Question 2

What are the 8 subunits of the Katp channel?

Answer 2

4 Potassium Inward Rectifier 6.2 Subunits (Kir6.2)

4 Sulphonylurea Receptor 1 Subunits (SUR1)

Question 3

ATP binds to what part of the Potassium channel causing closure?

Answer 3

Kir6.2

Question 4

What binds to SUR1 subunits to keep the channel open, maintaining the membrane potential?

Answer 4

ADP-Mg2+

Question 5

What do Sulphonylureas bind to?

Answer 5

SUR1
Displacing ADP-Mg2+ and closing the Katp channel.
Causes depolarisation and insulin release

Question 6

Name a Sulphonylurea?

Answer 6

Tolbutamide, Gliclazide and Glipizide

Question 7

Why are Sulphonylureas known as ‘insulin secretagogues’?

Answer 7

They cause pancreatic beta cells to release insulin

Question 8

Name some downsides of Sulphonylureas?

Answer 8

Weight gain

Hypoglycaemia (excessive insulin secretion)

Question 9

What are Glinides?

Answer 9

Drugs that work similar to Sulphonylureas but don’t cause hypo’s

Question 10

Name two incretins

Answer 10

GLP-1 (Glucagon Peptide Like-1)

GIP (Glucose Dependent Insulinotropic Peptide)

Question 11

Where are incretins released from?

Answer 11

Enteroendocrine cells in the small intestine

Question 12

How do incretins lower blood glucose?

Answer 12

Enhance insulin release from pancreatic beta cells (enhanced uptake of glucose)
Decreases glucagon release from pancreatic alpha cells (reduced production of glucose)

Question 13

What does DPP-4 do?

Answer 13

Terminates the action of incretins (GLP-1 and GIP)

Question 14

How do ‘Gliptins’ work

Answer 14

Inhibit the action of DDP-4, prolonging the action of GLP-1 and GIP

Question 15

What do all DPP-4 names have in common?

Answer 15

All have gliptin in the name

I.e saxagliptin, vildagliptin, linagliptin and alogliptin.

Question 16

What are incretin analogues?

Answer 16

Peptides that mimic the action of GLP-1 but are longer lasting.

Question 17

Name an incretin analogue?

Answer 17

Extenaide or Liraglutide

Question 18

Name a positive of incretin analogues?

Answer 18

Weight loss (loss of appetite)

Question 19

What does alpha-glucosidase do?

Answer 19

Break down starch and disaccharides to glucose

Question 20

Alpha-Glucosidase inhibitors are commonly/rarely used in the UK?

Answer 20

Rarely

Question 21

Metformin is an example of a … drug

Answer 21

Biguanide

Question 22

True/ False

Metformin is the first line treatment for T2DM?

Answer 22

FALSE HAHAHHAHA

Exercise is you FOOL

Question 23

What are the 2 main mechanisms of Metformin?

Answer 23

Reduces Hepatic Gluconeogenesis

Increases glucose uptake by skeletal muscle

Question 24

Positive aspects of Metformin? 5

Answer 24

Reduces microvascular risk
Oral administration 
Weight loss
No hypoglycaemia
Can be used with other agents

Question 25

Adverse effects of metformin?

Answer 25

``` GI upsets Lactic acidosis (rarely) ```

Question 26

Name a class of new drugs that block reabsorption of glucose in the kidneys? (i.e makes you pee out glucose)

Answer 26

SGLT2 Inhibitors

Question 27

Name a SGLT2 inhibitor?

Answer 27

Anything with gliflozin in the name. | Dapagliflozin, canagliflozin or empagliflozin