Anti- diabetic drugs SD

Question 1

What are the 3 fundamental strategies for anti-diabetic drugs?

Answer 1

Increase cellular sensitivity
Increase insulin release
Reduce/ delay glucose absorption

Question 2

What class of drug is metformin?

Answer 2

Biguanide

Question 3

What is the active ingredient in biguanides?

Answer 3

Guanidine (and galegin)

Question 4

What do biguanides do in order to lower hyperglycaemia?

Answer 4

Improve insulin sensitivity
Stimulate tissue uptake of glucose (esp muscle)
Reduces GI uptake of carbohydrates
Antihyperglycaemic effects

Question 5

What are the effects of metformin which make it 1st line therapy in fat people?

Answer 5

It doesn’t cause weight gain as it suppresses appetite

Question 6

What is lactic acidosis?

Answer 6

Lactic acid build up in the blood stream

Question 7

What is the half life of metformin?

Answer 7

1.5hrs

Question 8

Why are biguanides useful in late stage diabetes?

Answer 8

In late stages, B cell decline has occurred so insulin can not be produced as well. Metformin does not increase insulin secretion, it sensitises patient cells to it hence why it is useful

Question 9

What is kinase and what does it do?

Answer 9

An enzyme which adds phosphate groups

Question 10

Why are people with impaired renal function below 45ml/min not allowed metformin?

Answer 10

Increased risk of lactic acidosis, need working kidneys to remove the lactate

Question 11

What is glucogenesis?

Answer 11

Ability to metabolically generate new glucose

Question 12

What are the side effects of metformin?

Answer 12

Diarrhoea
Dyspepsia
Lactic acidosis

Question 13

What can make lactic acidosis worse/ life threatening?

Answer 13

Dehydration

Question 14

Name another insulin sensitiser group of drugs and an example within that group (not biguanides)

Answer 14

Thiazolidinediones- pioglitazone

Question 15

What does pioglitazone do to
a) IL-6
b) adiponectin

Answer 15

a) decreases IL-6
b) increases adiponectin

Question 16

Name 3 adverse effects with pioglitazone

Answer 16

1. weight gain
2. liver dysfunction (rare)
3. fluid retention (kidneys)

Question 17

Why should pioglitazone be avoided in patients with congestive heart failure?

Answer 17

Due to the risk of oedema (fluid retention in kidneys)

Question 18

What do secretagogues do?

Answer 18

Increase insulin production

Question 19

Name a 1st generation and a 2nd generation secretagogue

Answer 19

1st- tolbutamide
2nd- gliclazide

Question 20

What is the MOA of secretagogues?

Answer 20

They bind to the receptor, close potassium channels and open calcium channels to export insulin—> lower glucose, increase insulin

Question 21

When would sulphonylureas be used in diabetes?

Answer 21

Where metformin is contraindicated or if the patient is NOT over weight

Question 22

What is the MOA of sulphonylureas?

Answer 22

Stimulates B cells of the islet of Langerhans in the pancreas to release insulin which lowers glucose

Question 23

sulphonylureas are ineffective where there is no insulin production, why?

Answer 23

IF there is not insulin production this means there is no/ lack of B cells which means there are no B cells to drive to produce insulin.
Hence this drug is normally used in earlier stages on diabetes before a decline in B cells

Question 24

How is gliclazide metabolised and excreted? (which organs)

Answer 24

Metabolised by the liver
Excreted mainly by the kidneys

Question 25

Why is gliclazide less likely to cause hypoglycaemia compared to other sulphonylureas?

Answer 25

It only interacts with SUR1 not EPAC2 which also increases insulin levels hence decreasing glucose levels further---> hypo

Question 26

What is the new weight loss craze and how does it work?

Answer 26

GLP-1 Increases metabolism, insulin secretion and glucose break down

Question 27

Why do we use a DPP-4 enzyme inhibitor in diabetes?

Answer 27

Body naturally degrades GLP-1 though the DPP-4 enzyme, but GLP-1 lowers hyperglycaemia so we don't want it broken down. Hence we use DPP-4 inhibitors called gliptins which are competitive inhibitors of DPP-4 which help prolong GLP-1 and GIP activity to reduce glucose

Question 28

Give a named example of DPP-4 inhibitor

Answer 28

Sinagliptin

Question 29

Name a SGLT2 inhibitor and how it works

Answer 29

'Gliflozin' eg. dapagliflozin Works by inhibiting SGLT2 receptors by blocking kidney transporter so glucose is urinated out instead of recycled back into blood stream hence lowering glucose levels.

Question 30

What anti-diabetic drug alters glucose absorption?

Answer 30

SGLT2 inhibitors