PHARMACOLOGY

Question 1

Which 2 antihyperglycaemic drugs can cause weight gain and hypoglycaemia? (When used by themselves)

Answer 1

Sulfonylureas

Insulin

Question 2

Name 3 antihyperglycaemic drugs which can cause weight loss.

Answer 2

Metformin

GLP-1 Receptor Agonist

SGLT-2 Inhibitor

Question 3

What is the mechanism of action of metformin?

Answer 3

Reduces hepatic gluconeogenesis

Increases peripheral utilisation of glucose

Question 4

List 3 side effects of metformin

Answer 4

GIT Symptoms

Vitamin B12 deficiency

Lactic acidosis (rare, but should avoid in patients w/ conditions predisposing them to tissue hypoxia and acidosis)

Question 5

Why does metformin not have any effect in normoglycaemic states?

Answer 5

It does not stimulate insulin secretion

Question 6

How is metformin cleared?

Answer 6

90% is renally-cleared as the unchanged drug

Question 7

What is the mechanism of action of sulfonylureas?

Answer 7

Increases pancreatic insulin production (MAINLY)

Also reduces insulin uptake by the liver, decreases glucose output by the liver, and increases peripheral insulin sensitivity

Question 8

Describe one suitability issue of sulfonylureas

Answer 8

Can cause hypoglycaemia, so be cautious in patients who are at greater risk of this (e.g. living alone)

Can also cause weight gain

Is a sulfur drug, so there may be issues with allergic reactions

Question 9

What is the mechanism of action of DPP-4 inhibitors? (The gliptins)

Answer 9

Inhibits the action of dipeptidyl peptidase-4 enzyme, causing:

Increase in incretin hormones (incretins are normally released after a meal and stimulate lowering of the BGL)
↑insulin secretion
↓glucagon secretion

Question 10

Are DPP-4 inhibitors more or less effective than metformin and sulfonylureas?

Answer 10

Less effective

Question 11

What is the mechanism of action of SGLT-2 inhibitors, and how does this link to their adverse effects? (The gliflozins)

Answer 11

Inhibitors the sodium-glucose-cotransporter 2, decreasing glucose reuptake by the nephrons.

Side effects: classic diabetes symptoms (polyuria, polydipsia), but can also increase risk of UTIs, dehydration, and ketoacidosis

Question 12

Describe one suitability issue of SGLT-2 inhibitors

Answer 12

May be an issue in volume-depleted states due to osmotic diuretic effect, e.g. people taking diuretics

Question 13

What is the mechanism of action of GLP-1 receptor agonists? E.g. liraglutide

Answer 13

Agonists at the GLP-1 receptor (an incretin) to mimic the effects of GLP-1:

• Delays gastric emptying → slows glucose absorption and decreases appetite
• Increases insulin secretion and suppresses inappropriate glucagon secretion

Question 14

How are GLP-1 receptor agonists taken?

Answer 14

As an injection (since they are proteins)

Question 15

How does the MOA of GLP-1 receptor agonists cause side effects?

Answer 15

Related to delayed gastric emptying:

NV in up to 50%
Abdominal pain
Bloating
Increased risk of pancreatitis, cholelithiasis, cholecystitis