Diabetes

Question 1

Name 4 drugs commonly used for diabetes in London

Answer 1

Metformin, Sulphonylurea, Dipeptidyl peptidase 4, (Sodium glucose co-transporter ( SGLT-2) inhibitors

Question 2

What is the primary mechanism of metformin?

Answer 2

Activates AMPK in hepatocyte mitochondria – Inhibits ATP production.
Blocks gluconeogeneisisand thus reduce glucose output.

It blocks adenylate cyclase which promotes fat oxidation.

Helps to restore insulin sensitivity

Question 3

What is the drug target of metformin?

Answer 3

5’ AMP - activated protein kinase (AMPK)

Question 4

What are the main side effects of metformin?

Answer 4

GI side effects ( 20-30% patients) - abdominal pain, decreased appetite, diarrhoea, vomiting

[Slow increase in dose may improve tolerability]

Question 5

What extra information is relevant information of metformin?

Answer 5

It can accumulate in the liver and GI tract.
Most effective in the presence of endogenous insulin so is more effective with residual functioning pancreatic islet cells

Question 6

What is an example of dipeptidyl- peptidase 4 (DPP-4) inhibitors?

Answer 6

Sitagliptin

Question 7

What is the primary mechanism of dipeptidyl-peptidase (DPP-4) inhibitors?

Answer 7

Inhibiting DPP-4, present in vascular endothelium and can metabolise incretins in the plasma.
Incretins - help stimulate the prodduction of insulin when it is needed and reduce the production of glucagon when it is not needed.
Also slow down digestion and decrease appetite

Question 8

What is the drug target of dipeptidyl- peptidase (DPP-4) inhibitors?

Answer 8

DPP-4 in vascular endothelium

Question 9

What is the main side effects of dipeptidyl- peptidase (DPP-4) inhibitors?

Answer 9

Upper respiratory tract infections (5% patients) - flu like symptoms

Avoid in patients wirh pancreatitis

Question 10

Are there any extra information on dipeptidyl- peptidase (DPP-4) inhibitors?

Answer 10

Does not appear to cause weight gain
Only effective when residual functional pancreatic beta cell activity

Question 11

What is an example of sulphonylurea?

Answer 11

Gliclazide

Question 12

What is the primary mechanism of action of sulphonylurea?

Answer 12

Inhibit the ATP- sensitive potassium channels (KATP) channel on the pancreatic beta cell

Inhibition causes depolarisation which stimulates Ca++ influx and subsequent insulin vesicle exocytosis

Question 13

What is the main drug target of sulphonylurea?

Answer 13

ATP sensitive potassium channel

Question 14

What are the main side effects of sulphonylurea?

Answer 14

Weight gain
Hypoglycaemia

Question 15

Are there any extra information for sulphonylurea?

Answer 15

Augmenting insulin secretion
Effective only when some residual pancreatic beta cell function present

Weight gain mitigated by administration with metformin

Question 16

What is an example of sodium- glucose co-transporter (SGLT2) inhibitors?

Answer 16

Dapaglifozin

Question 17

What is the primary mechanism of SGLT-2 inhibitors?

Answer 17

SGLT-2 , proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion

Question 18

What is the drug target of SGLT-2 inhibitors?

Answer 18

SGLT-2 proximal convoluted tubule

Question 19

What are the main side effects of SGLT- 2 inhibitors?

Answer 19

Uro- genital infections ( 5% patients)
Can worse diabetic ketoacidosis

Question 20

Are there any extra information on SGLT-2 inhibitors that is relevant?

Answer 20

Can cause weight loss and reduction in BP
Less effective on patients with renal impairment

Question 21

Main side effect for pioglitazone and what organ it acts on

Answer 21

1. Heart failure
2. Liver

Question 22

What HbA1c does first and second line treatment come into play and what does the drug aim for

Answer 22

48mmol/mol - 48
58 mmol/mol - 53

Question 23

What does OCT-1 stand for, where is it found and what does it allow?

Answer 23

Organic cation transporter -1
Small bowel - absorption
Liver - distribution
PCT - excretion