Diabetes pharmacology

Question 1

Which drug is a first generation sulphonylurea?

Answer 1

Tolbutamide

Question 2

Which drugs are second generation sulphonylureas?

Answer 2

Glibenclamide

Glipizide

Question 3

How do sulphonylureas stimulate insulin release?

Answer 3

Displaces the binding of ADP-Mg2+ from the SUR1 subunit, closing the KATP channel, allowing the membrane depolarisation to occur that stimulates insulin release

Question 4

What is the difference between first and second generation sulphonylureas?

Answer 4

Second are more potent and longer acting

Question 5

What is the disadvantageous side effect of sulphonylureas?

Answer 5

Weight gain

Question 6

In which patients is the risk of hypoglycaemia caused by sulphonylureas increased?

Answer 6

Elderly

Impaired hepatic/renal function

Question 7

Which drugs are examples of glinides?

Answer 7

Repaglinide

Nateglinide

Question 8

How do glinides work?

Answer 8

Binds to SUR1 subunit at a benzamino site, closing the KATP channel and triggering insulin release

Question 9

Are sulphonylureas or glinides more likely to cause hypoglycaemia?

Answer 9

Sulphonylureas

Question 10

When are glinides taken and why?

Answer 10

Before meals

Combats post-prandial rise in glucose

Question 11

What do glucagon-like peptide 1 (GLP1) and glucose dependant insulinotropic peptide (GIP) do and when are they released?

Answer 11

Released in response to ingestion of food
GLP-1 and GIP stimulate insulin secretion from pancreatic beta cells and delay gastric emptying
GLP-1 decreases glucagon release from pancreatic alpha cells

Question 12

Which drugs mimic the action of GLP-1?

Answer 12

Incretin analogues

Question 13

Which drug is an incretin analogue?

Answer 13

Extenatide

Question 14

What are the effects of incretin analogues?

Answer 14

Increases insulin secretion
Suppresses glucagon secretion
Slows gastric emptying
Decreases appetite

Question 15

What are some of the advantages of using incretin analogues?

Answer 15

Cause modest weight loss

Reduce hepatic fat accumulation

Question 16

How is extenatide administered?

Answer 16

Subcutaneously twice daily

Question 17

What are some of the side effects of extenatide?

Answer 17

Nausea
Hypoglycaemia
Pancreatitis

Question 18

How do DPP-4 inhibitors/gliptins work?

Answer 18

Inhibit the actions of DPP-4 (a GLP-1 and GIP inhibitor), prolonging the effects of GLP-1 and GIP

Question 19

What are some examples of some gliptins?

Answer 19

Sitagliptin
Saxigliptin
Vildagliptin

Question 20

What are some of the advantages of using gliptins?

Answer 20

Weight neutral
Generally well tolerated
No hypoglycaemia

Question 21

How does acarbose work?

Answer 21

Inihbit alpha-glucosidase, stopping the breakdown of carbohydrates into absorbable glucose form
More carbohydrate is excreted in stools

Question 22

In which patients is acarbose used?

Answer 22

Patients whose T2DM is inadequately controlled by lifestyle changes and drugs

Question 23

What are the side effects of acarbose?

Answer 23

Flatulence
Bloating
Abdominal pain
Loose stools
Diarrhoea

Question 24

Which is the first line drug treatment for obese T2DM patients?

Answer 24

Metformin

Question 25

How does metformin work?

Answer 25

Reduces hepatic gluconeogenesis Reduces carbohydrate absorption Increases fatty acid oxidation Increases glucose uptake and utilisation in skeletal muscles

Question 26

What are the advantages of using metformin?

Answer 26

Causes weight loss Does not cause hypoglycaemia Prevents hyperglycaemia Can be used with other therapies

Question 27

When must use of metformin be stopped?

Answer 27

When kidney function declines | GFR <30, metformin stopped

Question 28

What are some of the adverse affects of metformin?

Answer 28

``` GI upsets (diarrhoea/nausea/anorexia) (Rarely) lactic acidosis ```

Question 29

Which is the only thiazolidinedione licenced for use in the UK?

Answer 29

Pioglitazone

Question 30

How do thiazolidinediones work?

Answer 30

``` Enhance the action of insulin at target tissues Promotes the genetic expression of: Lipoprotein lipase Fatty acid transport protein GLUT4 ```

Question 31

What are the desirable effects of thizolidinediones?

Answer 31

Promote fatty acid uptake and storage in adipocytes, rather than skeletal muscle and liver Reduced hepatic glucose output

Question 32

What are the adverse effects of thiazolidinediones?

Answer 32

Weight gain Fluid retention (Na+ reabsorption at kidney encouraged) Increases incidence of bone fractures

Question 33

Which is the only Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitor licesnced for use in the UK?

Answer 33

Dapagliflozin

Question 34

How do sodium-glucose cotransporter-2 (SGLT2) Inhibitors work?

Answer 34

Selectively blocks the reabsorption of glucose at the proximal tubule of the nephron to purposefully cause glucosuria This reduces blood glucose and can cause some weight loss

Question 35

What is the required treatment for type 1 diabetes?

Answer 35

Immediate insulin therapy

Question 36

What are the aims of insulin therapy for T1DM?

Answer 36

Avoid hypoglycaemia Reduce hyperglycaemia Reduce chronic complications

Question 37

Which insulins are examples of rapid acting analogues?

Answer 37

Humalog* (insulin lispro) NovoRapid Apidra

Question 38

Which insulins are short acting?

Answer 38

Humulin S (Human insulin) Actrapid Insuman Rapid

Question 39

Which insulin is a long acting analogue?

Answer 39

Lantus | Levemir

Question 40

Which insulin regimen aims to mimic normal endogenous insulin production?

Answer 40

Basal bolus regimen

Question 41

What is involved in the basal bolus insulin regimen?

Answer 41

One long acting injection to maintain insulin levels | Three rapid acting injections before meals to combat post-prandial rise in glucose

Question 42

How is initial insulin requirement in basal bolus regimen calculated?

Answer 42

``` 0.3 units/kg body weight Divide 50% basal 50% prandial e.g. 60kg => 18 units 9 units basal 3/3/3 units prandial ```