Diabetes Pharm

Question 1

what is the MOA of metformin?

Answer 1

activates AMPK in hepatocyte mitochondria, inhibiting ATP production
blocks gluconeogenesis and subsequent glucose output
also blocks adenylate cyclase so promotes fat oxidation

Question 2

what is the drug target of metformin

Answer 2

5’-AMPK in hepatocyte mitochondria

and adenylate cyclase

Question 3

what are the main side effects of metformin?

Answer 3

GI side effects - abdo pain, reduced appetite, diarrhoea, vomiting

Question 4

why does metformin accumulate in the liver (therapeutic effect) and GI tract (side effect)?

Answer 4

as it is highly polar, requires organic cation transporter-1 to access tissues (present in these places)

Question 5

when is metformin most effective?

Answer 5

in patients with remaining functional pancreatic islet cells

Question 6

what is the MOA for dipeptidyl-peptidase 4 inhibitors? (DPP-4)
sitagliptin

Answer 6

inhibits action of DPP-4 in vascular endothelium which normally breaks down incretins in the plasma
therefore limits breakdown of incretins and prolongs their effects

Question 7

what are incretins?

Answer 7

secreted by enteroendocrine cells, stimulate production of insulin when needed and reduce glucagon.
also slow down digestion and decrease appetite

Question 8

give examples of incretins?

Answer 8

GLP-1

GIP

Question 9

what is the drug target for DPP-4 inhibitors? (sitagliptin)

Answer 9

DPP-4 enzyme in vascular endothelium

Question 10

what are the main side effects of DPP-4 inhibitors?(sitagliptin)

Answer 10

upper respiratory tract infections, flu like symptoms

less commonly - severe allergy

Question 11

what are the contraindications for DPP-4? (sitagliptin)

Answer 11

pancreatitis

Question 12

what is the MOA of sulphonylureas? (gliclazide)

Answer 12

inhibits ATP-sensitive K+ channel on pancreatic beta cell
inhibition causes depolarisation of beta cell which stimulates Ca2+ influx
subsequent insulin vesicle exocytosis

aka causes increased release of insulin

Question 13

what is the drug target for sulphonylureas? (gliclazide)

Answer 13

ATP-sensitive potassium channel on pancreatic beta cells

Question 14

what are the main side effects of sulphonylureas? (gliclazide)

Answer 14

weight gain

hypoglycaemia

Question 15

what is the MOA of SGLT2 inhibitors? (dapaglifozin)

Answer 15

reversibly inhibits sodium-glucose cotransporter 2 in PCT

reduces glucose reabsorption and increases urinary glucose excretion

Question 16

what is the drug target for SGLT2 inhibitors? (dapaglifozin)

Answer 16

sodium-glucose cotransporter 2 in proximal convoluted tubule

Question 17

what are the main side effects of SGLT2 inhibitors? (dapaglifozin)

Answer 17

urogenital infections
slight decrease in bone formation
can worsen diabetic ketoacidosis
weight loss
BP reduction

Question 18

what are SGLT2 inhibitors dependent on and therefore its contraindications? (dapaglifozin)

Answer 18

renal function

therefore less effective in patients with renal impairment

Question 19

when should metformin be prescribed in patients with T2DM?

Answer 19

HbA1c above 48mmol/mol even with lifestyle intervention

Question 20

when is the first intensification of metformin treatment for T2DM?

Answer 20

HbA1c 58mmol/mol despite on metformin

dual therapy with 2 of DPP4i, SGLT2i, gliclazide, pioglitazone

Question 21

first line treatment for HbA1c over 48 when already given lifestyle advice

Answer 21

Metformin

Question 22

first line treatment for HbA1c over 58

Answer 22

Metformin

Question 23

why may you not choose to prescribe sulphonylureas (gliclazide)

Answer 23

can cause weight gain - not for people with already high B,I

hypoglycaemia risk

Question 24

what patients would you choose to prescribe GLP-1 agonists and SGLT-2 inhibitors to?

Answer 24

patients with CVD risk - prevention

Question 25

when are thiazolidinediones contraindicated (pioglitazone)

Answer 25

heart failure

Question 26

what diabetes drug is most tolerable

Answer 26

DPP-4 inhibitors

moderately effective

Question 27

example of DPP-4 inhibitor

Answer 27

sitagliptin

Question 28

example of GLP-1 agonist

Answer 28

liraglutide

Question 29

example of sulphonylurea

Answer 29

gliclazide

Question 30

example of SGLT-2 inhibitor

Answer 30

empagliflozin

Question 31

example of thiazolidinedione

Answer 31

pioglitazone