Diabetes Pharmacology

Question 1

List drug classes that increase secretion of insulin through insulin-independent action

Answer 1

Sulphonylureas
Incretin analogues
DPP-4 inhibitors

Question 2

List drug classes that decrease insulin resistance and reduced hepatic glucose output through insulin-dependent action

Answer 2

Biguanides

Thiazolidinediones (TZD’s)

Question 3

List a drug class that slows glucose absorption from the GI tract through insulin-independent action

Answer 3

Alpha-glucosidase inhibitors

Question 4

List a drug class that blocks reabsorption of glucose in the kidneys through insulin-independent action

Answer 4

SGLT2 inhibitors

Question 5

Through which transporter does glucose enter the beta-cell in the pancreas?

Answer 5

GLUT2

Question 6

What effect does ATP in the beta-cell of the pancreas have on K channels?

Answer 6

Closes them, causing depolarisation of the membrane

Question 7

How is insulin released following depolarisation of the membrane of the beta-cell?

Answer 7

Depolarisation causes opening of Ca channels, causing insulin-containing vesicles to exocytose

Question 8

List the components of the Katp channel

Answer 8

4x Kir6.2 units

4x SUR1 units

Question 9

Which part of the Katp channel does ATP bind to?

Answer 9

Kir6.2 unit

Question 10

What binds to the SUR1 part of the Katp channel? What does this cause?

Answer 10

ADP-Mg

Repolarisation to inhibit insulin secretion

Question 11

How do sulphonylurea drugs work?

Answer 11

Displace ADP-Mg from SUR1 on Katp channel to cause depolarisation to promote insulin release

Question 12

The effect of sulphonylurea drugs is independent of glucose conc. True/False?

Answer 12

True

Question 13

Give examples of sulphonylureas

Answer 13

Tolbutamide
Glibenclamide
Glipizide

Question 14

What is the main difference between tolbutamide and glibenclamide?

Answer 14

Glibenclamide is more potent and longer acting

Only need to take glibenclamide 1x/day

Question 15

Can sulphonylureas cause hypoglycaemia?

Answer 15

Yes

Greater risk with long-acting agents

Question 16

How do glinides differ from sulphonylureas?

Answer 16

Bind to specific part of SUR1

Rapid action - less likely to cause hypoglycaemia

Question 17

Incretin hormones stimulate production of insulin. What are the two main endogenous incretin hormones?

Answer 17

GLP-1

GIP

Question 18

GLP-1 and GIP enhance insulin production. What effect does GLP-1 have on glucagon?

Answer 18

Decreases glucagon release from alpha-cells

Question 19

Give an example of an incretin analogue

Answer 19

Extenatide

Question 20

Which enzyme rapidly inhibits the action of incretin hormones?

Answer 20

DPP-4

Question 21

How do DPP-4 antagonists (gliptins) work?

Answer 21

Inhibit DPP-4 to prolong actions of GLP-1 and GIP

Question 22

Give an example of a DPP-4 inhibitor

Answer 22

Sitagliptin

Question 23

What is the function of alpha-glucosidase in the intestine?

Answer 23

Breaks down carbohydrate into absorbable glucose

Question 24

How do alpha-glucosidase inhibitors work?

Answer 24

Inhibit alpha-glucosidase to delay absorption of glucose, thus reducing post-prandial increase in blood glucose

Question 25

Give an example of an alpha-glucosidase inhibitor

Answer 25

Acarbose

Question 26

Acarbose has great risk of hypoglycaemia. True/False?

Answer 26

False | No risk whatsoever

Question 27

What is the 1st line therapy for type 2 diabetes?

Answer 27

Biguanides (metformin)

Question 28

What is the proposed action of metformin?

Answer 28

Reduces hepatic gluconeogenesis by stimulating AMPK | Enhances glucose uptake by muscle

Question 29

Does metformin cause hypoglycaemia?

Answer 29

No

Question 30

Metformin causes weight gain. True/False?

Answer 30

False | Weight loss

Question 31

List a significant adverse effect of metformin

Answer 31

Lactic acidosis (as a result of less gluconeogenesis)

Question 32

How do TZDs work?

Answer 32

Agonist of PPAR-alpha which associated with RXR to enhance transcription of genes encoding insulin signalling (ultimately enhancing insulin action at tissues)

Question 33

Which transporter moves glucose into skeletal muscle?

Answer 33

GLUT4

Question 34

TZDs can cause weight gain. True/False?

Answer 34

True

Question 35

How do SGLT2 inhibitors work?

Answer 35

Block reabsorption of glucose in convoluted tube of nephron to cause glycosuria

Question 36

Name a SGLT2 inhibitor

Answer 36

Dapagliflozin

Question 37

What is the main adverse effect/risk of SGLT2 inhibitors?

Answer 37

Increased risk of UTI | Thrush

Question 38

Give an example of a TZD

Answer 38

Pioglitazone