Diabetes Drugs

Question 1

What is the mechanism of Sulphonylurea?

Answer 1

INSULIN SENSITISER

Causes pancreatic C-cell insulin secretion so requires functional mass of B-cells

Question 2

Give examples of Sulphonylurea (short and long-acting)

Answer 2

Short-acting - Tolbutamide

Long-acting - Glibenclamide, gliclazide, glipizide

Question 3

Main side effects of sulphonylurea and why

Answer 3

Hypoglycaemia - excessive insulin secretion

Weight gain - increased anabolic effect, increased appetite, decreased urinary loss of glucose

Question 4

In which patients should you avoid long-acting sulphonylurea?

Answer 4

Elderly
Pregnant women
CKD (or any reduced hepatic/renal function)

Question 5

When would sulphonylureas be used?

Answer 5

• 1st line if intolerant to metformin (or weight loss)
• 2nd line in conjunction with metformin
• 3rd line in conjunction with metformin and thiazolidinediones

Question 6

When are Glinides used?

Answer 6

In conjunction with metformin and thiazolidinediones

Question 7

What is safer in CKD - SUs or glinides?

Answer 7

Glinides

Safer than SUs as mainly subject to hepatic metabolism

Question 8

In which patients should Glinides be avoided?

Answer 8

Severe hepatic impairment
Pregnancy
Breast feeding

Question 9

Give examples of Glinides

Answer 9

Repaglinide

Nateglinide

Question 10

Explain the action of DDP-4 inhibitors

Answer 10

Competitively inhibits DDP-4 enzyme = increased plasma insulin

Normal DDP-4 action = terminate GLP-1 and GIP action which terminated insulin secretion

Question 11

Give examples of DDP-4 inhibitors (Gliptin)

Answer 11

Sitagliptin

Saxagliptin
Vildagliptin

Question 12

What is the main side effect of sitagliptin

Answer 12

Nausea

NO hypoglycaemia and weight neutral

Question 13

What are Incretin analogues?

Answer 13

Peptides that mimic action of GLP-1

Longer lasting as resist the breakdown by DDP-4

Question 14

What in the mechanism of Incretin analogues?

Answer 14

Bind as agonists to GPCR GLP-1 receptors > increases intracellular cAMP conc. in pancreatic B-cells > stimulates insulin expression + release

Also suppresses glucagon secretion, slows gastric emptying + decreases appetite

Question 15

Side effects of incretin analogues

Answer 15

• Nausea
• Pancreatities (Rare)

NO hypoglycaemia

Question 16

What is the function of a-glucosidase?

Answer 16

Brush border enzyme

Breaks down starch and disaccharides to absorbable glucose

Question 17

Give examples of a-glucosidase inhibitors

Answer 17

Acarbose
Miglitol
Voglibose

Question 18

What are the main adverse effects of a-glucosidase inhibitors

Answer 18

GI TRACT > flatulence, loose stools, diarrhoea, abdominal pain, bloating

NO risk of hypoglycaemia

Question 19

What patients would be prescribed an a-glucosidase inhibitor?

Answer 19

T2DM patients with in adequately controlled diabetes through life style measures or other drugs (e.g. SUs)

Question 20

Who is Metformin used for?

Answer 20

First line agent for all T2DM patients irrespective of obesity (with normal hepatic/renal function)

Question 21

What is the mechanism of Metformin?

Answer 21

• reduces hepatic gluconeogenesis
• increases glucose uptake + utilization by skeletal muscle
• Reduces carb absorption
• Increase fatty acid oxidation

Question 22

What are the other desirable effects of Metformin?

Answer 22

• reduce microvascular complications
• oral administration
• Prevents hyperglycaemia
• weight loss

Question 23

Adverse effects of Metformin?

Answer 23

• GI upset (nausea, diarrhoea, anorexia)

- Lactic acidosis (rare) => excessive alcohol consumption can contribute

Question 24

What is the action of TZDs?

Answer 24

Enhance action of insulin at target tissues (does not affect insulin secretion)

REDUCE INSULIN RESISTANCE

Question 25

Effects of TZDs?

Answer 25

- Promote fatty acid uptake + storage in adipocytes - Reduce hepatic glucose output - Enhance peripheral glucose uptake NO hypoglycaemia

Question 26

What is the gene pathway of TZDs?

Answer 26

1) Agonist agents of PPAR-y receptor (associates with RXR) 2) Activated PPARy-RXR = transcription factor 3) Promotes gene expression involved in insulin signalling + lipid metabolism

Question 27

Adverse effects of TZDs?

Answer 27

- Weight gain - Fluid retention (promotes Na+ reabsorption) - Hepatotoxicity (not pioglitazone) - Bone fractures

Question 28

When might Pioglitazone (TZDs) be used?

Answer 28

In combination with metformin or SUs to achieve adequate control of blood glucose

Question 29

What is the mechanism of SGLT2 inhibitors?

Answer 29

Selectively block the reabsorption of glucose by SGLT2 in proximal tubule of kidney nephron = causes Glucosuria

Question 30

What are the effects of SGLT2 inhibitors?

Answer 30

- Blood glucose decrease (little risk of hypoglycaemia) | - Calorific loss > weight loss