pharmacology diabetes

Question 1

What do people with T2D usually present with?

Answer 1

Hyerglycaemia, raised HbA1c, hypertension, dyslipidaemia

Question 2

What is their therapeutic objective for someone with T2D?

Answer 2

Decrease HbA1C, reduce hypertension, weight loss, help dyslipidaemia

Question 3

Are lifestyle changes effective for T2?

Answer 3

If they adhere to them they are as effective as medications

Question 4

What do you usually prescribe first and afterwards for T2D?

Answer 4

First prescribe lifestyle intervention and after that metformin if needed

Question 5

What ahppens if HbA1C rises to 48mmol/l on lifestyle intervention?

Answer 5

Prescribe metfomin (oral 500mg/day)

Question 6

What is standard dose of metformin?

Answer 6

500mg/day oral

Question 7

What happens if on metformin, they have an intensificiation that rises HbA1C to 58?

Answer 7

Consider dual therapy (eg with DPP4 inhibitor

Question 8

What happens if second intesification ?

Answer 8

consider triple therapy

Question 9

What is the molecular structure of metformin?

Answer 9

Metformin is polar and water soluble and therefore needs organic cation transporter 1 in order to be transported across bilayer

Question 10

Where is OCT-1 (organic cation tranpsorter) present and why?

Answer 10

OCT-1 is expressed in hepatocytes (for therapeutic effect), small intestine enterocytes (for absorption), kidney (for excretion)

Question 11

Why monitor kidney function when on metformin?

Answer 11

because it can put them at risk of lactic acidosis as inhibits first step of gluconeogenesis leading to accumulation of lactic acid.

Question 12

eGFR cut off for metformin?

Answer 12

eGFR <30 is cut off (metformin cannot be used due to risk of lactic acidosis)

Question 13

What are side effects of metformin? What should you recommend?

Answer 13

GI symptoms. Tell them to after food or switch to better preparation (eg sustained release metformin)

Question 14

What is the mechanism of metformin?

Answer 14

It activates AMPK in hepatocyte mitochondria inhibiting ATP production and thus inhibiting gluconeogenesis (decreases HGO). It also blocks adenylyl cyclase which promotes fat oxidation. Both increase insulin sensitivity.

Question 15

What is the drug target of metformin?

Answer 15

AMPK in hepatocyte mitochondria

Question 16

What are side effects of metformin? What can help with this?

Answer 16

GI symptoms - abdominal pain, diarrhoea, nausea, vomiting. (usually at higher doses). Slowly increasing the dose can help with these symptoms. Also take after food and maybe use sustained release metformin instead.

Question 17

When is metformin most effective?

Answer 17

Most effective in presence of endogenous insulin

Question 18

What is the structure of metformin and its implications?

Answer 18

Highly polar (water soluble) and needs OCP-1 transporter for transport. This transporter expressed in hepatocytes (therapeutic effect), enterocytes (GI side effects) and kidney (excretion)

Question 19

What is DPP-4 inhibitor example?

Answer 19

sitagliptin

Question 20

What is the mechanism of action of DPP-4 inhibitors?

Answer 20

DPP-4 is involved in the metabolism of incretins like GLP-1 (which increase insulin production and satiety). Therefore DPP4 inhibitors inhibit DPP4 and increase incretins.

Question 21

Where is the site of action of DDP-4 inhibitors?

Answer 21

vascular endothelium

Question 22

What are side effects of DPP4 inhibitors?

Answer 22

upper respiratory tract infections (flu-like symptoms)

Question 23

when should DPP4 inhibitors not be used?

Answer 23

pancreatits

Question 24

do DPP4 inhibitors cause weight gain?

Answer 24

no

Question 25

when are DPP4 inhibitors most effective?

Answer 25

residual β-cell function (insulin present)

Question 26

What is an example of a sulphonylurea?

Answer 26

gliclazide

Question 27

What is the mechanism of sulphonylurea?

Answer 27

Inhibits ATP sensitive potassium channels on pancreatic β cells, causing depolarisation, calcium influx and therefore exocytosis of insulin / insulin production.

Question 28

What is the site of action of sulphonylurea?

Answer 28

ATP sensitive potassium channels on pancreatic β cells

Question 29

What is side effect of sulphonylurea?

Answer 29

Weight gain & hypoglycaemia

Question 30

when is sulphonylurea drugs most effective?

Answer 30

residual β function (insulin present)

Question 31

how can weight gain caused by sulphonylurea be mitigated?

Answer 31

concurrent use with metformin

Question 32

What is example of SGLT2 inhibitor?

Answer 32

dapaglifozin

Question 33

What is the mechanism of SGLT2 inhibitor?

Answer 33

Binds on SGLT2 on PCT in kidney in order to inhibit sodium/glucose transporter, prevent glucose reabsopriton and increase glucose excretion in urine

Question 34

What is the site of action of SGLT2 inhibitors?

Answer 34

SLT2 on PCT in kidney

Question 35

What are the side effects of SGLT2 inhibitors?

Answer 35

Uro-genital infections due to increased glycosuria, slight decrease in bone formation and can worsen diabetic ketoacidosis

Question 36

What are extra benefits of SLT2 inhibitors?

Answer 36

weight loss and decrease in BP

Question 37

when is SGL2 inhibitor less effective and why?

Answer 37

depends on renal function so less effective in those with renal impairement