Diabetes

Question 1

What is the primary mechanism of action of metformin?

Answer 1

activates AMPK in hepatocyte mitochondria
this inhibits ATP production
this blocks gluconeogenesis and subsequent glucose output
Blocks adenylate cyclase which promotes fat oxidation
this restores insulin sensitivity

Question 2

What is the drug target of metformin?

Answer 2

5-AMP-activated protein kinase - AMPK

primary site of metformin action is the hepatocyte mitochondria

Question 3

What are the side effects of metformin?

Answer 3

Abdominal pain
Decreased appetite
Diarrhoea
Vomiting

Question 4

When is metformin most effective?

Answer 4

Presence of endogenous insulin so is most effective with some residual functioning pancreatic islet cells

Question 5

What transporter does metformin require to access tissues?

Answer 5

OCT-1, so it can accumulate in liver (therapeutic effect) and gastrointestinal tract (side effect)

Question 6

What is an example of dipeptidyl-peptidase 4 inhibitor?

Answer 6

Sitagliptin

Question 7

What class of drugs does sitagliptin belong to?

Answer 7

DPP-4 inhibitor

Question 8

What is the primary mechanism of action of DPP4 inhibitors?

Answer 8

Inhibit DPP4

Question 9

What is DPP-4?

Answer 9

An enzyme present in vascular endothelium and can metabolise incretins in the plasma. Incretins are secreted by enteroendocrine cells and help stimulate the production of insulin, and reduce the production of glucagon by the liver when it is not needed.

Question 10

What are incretins?

Answer 10

Incretins are secreted by enteroendocrine cells and help stimulate the production of insulin, and reduce the production of glucagon by the liver when it is not needed.

Question 11

What is an example of an incretin?

Answer 11

GLP-1

Question 12

What is the primary site of DPP4 inhibitor action?

Answer 12

The vascular endothelium - where DPP4 is located

Question 13

What are the side effects of DPP4 inhibitors?

Answer 13

Upper respiratory tract infection 
Flu like symptoms 
Headache
Runny nose 
Sore throat

Question 14

Why isn’t sitagliptin administered to patients with pancreatitis?

Answer 14

It’s associated with a higher risk of pancreatitis

Question 15

Give an example of a sulphonylurea

Answer 15

Gliclazide

Question 16

What is the primary mechanism of action of sulphonylurea?

Answer 16

Inhibits the ATP-sensitive potassium channel on the pancreatic beta cell
This channel controls beta cell membrane potential.
inhibition causes depolarisation
which stimulates Ca2+ influx
and subsequent insulin vesicle exocytosis

Question 17

What is the primary site of action of sulphonylureas?

Answer 17

Pancreatic beta cells - ATP sensitive potassium channel

Question 18

What are side effects of sulphonylurea?

Answer 18

Hypoglycaemia

Weight gain

Question 19

How to mitigate weight gain when administering sulphonylurea?

Answer 19

Concurrently administer with metformin

Question 20

Give an example of sodium glucose co transporter inhibitors (SGLT2)

Answer 20

Dapaglifozin

Question 21

What is the primary mechanism of action of SGLT2 inhibitors?

Answer 21

Reversibly inhibits sodium glucose co transporter 2 in the renal proximal convoluted tubule
to reduce glucose reabsorption and
increase urinary glucose excretion

Question 22

What is the drug site of SGLT2 inhibitor action?

Answer 22

SGLT2 on the proximal convoluted tubule

Question 23

What are the side effects of SGLT2?

Answer 23

Urogenital infections
Decrease in bone formation 
Worsens diabetic ketoacidosis
Weight loss 
Blood pressure reduction

Question 24

Which drug class used to treat diabetes is less effective in patient with renal impairment?

Answer 24

SGLT2 inhibitor