Diabetes

Question 1

What are the four main classes of drugs used to treat Diabetes?

Answer 1

Metformin
DPP-4 Inhibitor
Suphonylurea
SGLT-2 Inhibitor

Question 2

Describe the mechanism of action for Metformin

Answer 2

Activates AMP Kinase which blocks ATP production
hence gluconeogenesis is inhibited
Also Inhibits Adenylate cyclase which promotes fat oxidation
Both help to restore insulin sensitivity

Question 3

What is the drug target of Metformin?

Answer 3

5’ - AMP activated protein Kinase = ENZYME DRUG TARGET

Question 4

Where is the drug target of Metformin located?

Answer 4

hepatocyte mitochondria

Question 5

what are the side effects of Metformin?

Answer 5

GI Side effects = Abdo pain, nausea, diarrhoea, vomiting

Question 6

Why does metformin accumulate in the liver and the GI Tract?

Answer 6

The drug is highly polar and requires organic cation transporter-1 to access tissues

Question 7

What is the main example of a DPP4 Inhibitor?

Answer 7

Sitagliptin

Question 8

Describe the mechanism of action of Sitagliptin

Answer 8

Work by inhibiting the action of DPP-4.

This enzyme is present in vascular endothelium and can metabolise incretins in the plasma.

Therefore more incretins present, so more insulin produced

slows down digestion and decreases appetite

Question 9

What is the drug target of sitagliptin and where is this target found?

Answer 9

DPP-4, found in the vascular endothelium

Question 10

What are the side effects of Sitagliptin?

Answer 10

Upper respiratory tract infections
Flu-like symptoms
Serious allergic reactions

Question 11

Why might sitagliptin be chosen over other Diabetes drugs?

Answer 11

Unlike others, doesn’t cause weight gain

Question 12

What does sitagliptin need to be effective?

Answer 12

Since it works by augmenting insulin secretion, they are therefore only effective when some residual beta cell activity is present

Question 13

What is the mechanism of action for sulphonylurea?

Answer 13

Inhibit the ATP-sensitive potassium (KATP) 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 14

What is an example of a sulphonlyurea?

Answer 14

Gliclazide

Question 15

What is the drug target of Gliclazide and where is it found?

Answer 15

ATP sensitive K+ channels
In the pancreatic beta cells

Question 16

What are the side effects of Gliclazide?

Answer 16

Weight gain
Hypoglycaemia

Question 17

What type of drug is Dapaglifozin?

Answer 17

SGLT2 Inhibitor

Question 18

what is the mechanism of action for dapaglifozin?

Answer 18

Reversibly inhibits sodium-glucose co-transporter 2 (SGLT2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.

Question 19

What is the drug target for dapaglifozin and where?

Answer 19

SGLT2 - proximal convoluted tubule

Question 20

What are the side effects of dapaglifozin?

Answer 20

Urogenital infections due to increased glucose load
Decrease in bone formation
Weight loss, and lowers blood pressure

Question 21

When are SGLT2 inhibitors not effective?

Answer 21

In patients with renal impairment

Question 22

How do you mitigate the side effects of sulphonylureas?

Answer 22

concurrent metformin administration

Question 23

Which drug can worsen diabetic ketoacidosis and must be stopped immediately?

Answer 23

Dapaglifozin