Diabetes

Question 1

Primary mech. of metformin

Answer 1

activates AMPK in hepatocyte mitochondria to inhibit ATP
blocks gluconeogenesis (and more glucose output)
blocks adenylate cyclase to help fat oxidation
= help restore insulin sensitivity

Question 2

Metformin drug targets?

Answer 2

AMPK (5’- Activated protein kinase)

in hepatocyte mitochondria

Question 3

Metformin side effects

Answer 3

GI (20-30% of patients)
Abdominal pain, low appetite, diarrhoea, vomiting)
esp in high doses
slowly increasing dose can help improve tolerability instead

Question 4

How does metformin have therapeutic and side effects? (3 marks)

Answer 4

accumulates in liver (therapeutic) and in GI tract (side effect) as it needs organic-cation-transporter1 (OCT-1) to access tissues because its v polar (3 marks)

Question 5

examples of DPP-4 inhibitors

Answer 5

Dipeptide Peptidase 4 inhibitors

=Sitagliptin

Question 6

Prim mech of DPP-4 inhibitors?

Answer 6

inhibit DPP-4
present in vascular endothelium and metabolises incretins in plasma

basically stops incretic metabolism

Question 7

what do incretins do

Answer 7

Incretins (e.g. GLP-1) are secreted by enteroendocrine cells and help stimulate the production of insulin when it is needed (e.g. after eating) and reduce the production of glucagon by the liver when it is not needed (e.g. during digestion). Incretins also slow down digestion and decrease appetite.

Question 8

sitaglipin drug target

Answer 8

DPP-4 inhibitor

mainly in vascular endothelium

Question 9

examples of sulphonylurea

Answer 9

Glicazide

Question 10

Prim mech of sulphonylurea

Answer 10

inhibit KATP channel on pancreatic beta cells, causes depolarisation and Ca2+ influx causes insulin vesicle exocytosis

Question 11

what does the KATP channel do?

Answer 11

the ATP-sensitive potassium (KATP) channel on the pancreatic beta cell. This channel controls beta cell membrane potential

Question 12

Drug target of sulphonylurea

Answer 12

KATP channel in pancreatic beta cells

Question 13

Glicazide side effects?

Answer 13

weight gain

hypoglycemia

Question 14

When are sulphonylureas most effective?

Answer 14

The sulfonylureas act mainly by augmenting insulin secretion and consequently are effective only when some residual pancreatic beta-cell activity is present.

Question 15

SGLT2 inhibitor example and full form?

Answer 15

Sodium-glucose co-transporter (SGLT2) inhibitors

Dapaglifozin

Question 16

Primary mech. of SGLT2 inhibitors?

Answer 16

SGLT2 inhibited in PCT so less glucose reabsorbed and more is excreted in urine

Question 17

Dapaglifozin drug target?

Answer 17

SGLT2 in PCT

Question 18

SGLT2 inhibitor side effects

Answer 18

Uro-genital infections due to increased glucose load,
slight bone formation decrease,
DKA can worsen (then must stop immediately)

Question 19

in what patients can SGLT2 inhibitors be less effective?

Answer 19

SGLT2i action depends on normal renal fucntion so they are less effective in patients with renal impairment

Question 20

other (kinda positive) side effects of SGLT2 inhibitors

Answer 20

weight loss and lower BP