Diabetes

Question 1

What is the action mechanism of metformin?

Answer 1

Activates the AMPK in hepatocyte mitochondria. This inhibits ATP production blocking gluconeogenesis and therefore glucose output. Also blocks adenylate cyclase which promotes fat oxidation. Both help restore insulin sensitivity.

Question 2

What is the action mechanism of DDP4 inhibitors?

Answer 2

Inhibits DDP-4 which metabolises incretins on the vascular endothelium. Therefore plasma incretins are increased

Question 3

What is the action of incretins?

Answer 3

Eg GLP-1 secreted by enteroendocrine cells and help stimulate insulin and reduce production of glucagon by liver when it’s not needed.
Incretins also slow digestion and decrease appetite

Question 4

What is the action mechanism of sulphonylureas?

Answer 4

Inhibit ATP potassium sensitive channel on pancreatic beta cells. Inhibition of this channel promotes depolarisation which stimulates Ca2+ influx and therefore insulin vesicle exocytosis

Question 5

What is the action mechanism of SGLT2 inhibitors?

Answer 5

Inhibits sodium-glucose co-transporter 2 in the renal proximal convoluted tubule (kidney) to reduce glucose reabsorption and increase glucose urinary excretion

Question 6

When is SGLT-2 inhibitor most effective?

Answer 6

When there is normal renal function

Question 7

When are metformin, DPP-4 inhibitors and sulphonylureas most effective?

Answer 7

When there is residual pancreatic beta cell activity (endogenous insulin)

Question 8

What are the drug name endings for each drug type?

Answer 8

DPP-4: -gliptin
SULPHONYLUREAS: -gliclazide
SGLT-2: -gliflozin

Question 9

Metformin is highly polar. What needs to happen in order to metabolise it and what does its polarity explain?

Answer 9

Metformin is carried by OCT-1 transporter to access tissues. The fact that it’s polar means it can accumulate in gastrointestinal area causing side effects

Question 10

What are the side effects of Metformin?

Answer 10

GI side effects
Nausea
Diarrhoea
Vomiting
Abdominal pain

Question 11

What are the side effects of DPP-4 inhibitors?

Answer 11

Upper respiratory tract infections
Headache
Runny nose
Sore throat

Question 12

What are the side effects of sulphonylureas? What can be done to combat them?

Answer 12

Hypoglycaemia
Weight gain- can be combatted by taking Metformin as well

Question 13

What are the side effects of SGLT-2 inhibitors?

Answer 13

UTI
Weight loss

Question 14

Describe the process of treatment evaluation in T2 diabetes

Answer 14

HBA1c > 48mmol: lifestyle advice & metformin
HBA1c > 58mmol: Metformin & any other drug