Session 4 - Drugabetes

Question 1

What is a first line pharmacological treatment for diabetes?

Answer 1

Sulphonylureas (insulin release stimulants)

Question 2

Give three examples of suphonylureas (include half lives and duration of action)

Answer 2

 Tolbutamide (t½ ~ 4hrs, duration of action 6-12hrs)
 Glibencamide (t½ ~ 10hrs, duration of action 18-24hrs)
 Glipizide (t½ ~ 7hrs, duration of action 16-24hrs)

Question 3

What are indications for sulphonylureas

Answer 3

 Diabetes mellitus, in patients with residual β-cell activity

Question 4

Give four contraindications for suphonylureas

Answer 4

 Breastfeeding women, elderly, renal and hepatic insufficiency

Question 5

What is the mechanism of action of sulphonylureas

Answer 5

 Sulphonylureas antagonise β-cell K+/ATP activity, resulting in depolarisation. Voltage gated Ca2+ channels open, Ca2+ entry causes insulin vesicle fusion with cell membrane

Question 6

What adverse reactions can sulphonylureas cause? (3)

Answer 6

 Hypoglycaemia
 GI disturbance
 Weight gain

Question 7

What drug-drug interactions can sulphonylureas cause?

Answer 7

Highly protein bound

Question 8

What’s one of the most important second-line treatments for T2 diabetes?

Answer 8

Biguanides (metformin)

Question 9

What are the indications for metformin?

Answer 9

 Type II diabetes – Endogenous insulin presence required

Question 10

What are the contraindications for metformin?

Answer 10

 Compromised Kidney, lung and liver function

Question 11

What is the mechanism of action for metformin?

Answer 11

 Unclear – Precise actions under current study
 Increases insulin receptor sensitivity, enhancing skeletal and adipose glucose uptake
 Inhibits hepatic gluconeogenesis
 Reduces hyperglycaemia, but does not induce hypoglycaemia

Question 12

What 2 adverse drug rections for metformin?

Answer 12

 GI disturbances – ameliorated by slow dose titration

 Lactic Acidosis

Question 13

Give another two other types of insulin sensitiser, other than biguanide?

Answer 13

`Thiazolidinediones

Meglitidines

Question 14

Give two examples of Thiazolidinediones

Answer 14

 Rosiglitazone

 Pioglitazone

Question 15

What are the indications for Thiazolidinediones

Answer 15

 Uncontrolled non insulin dependant diabetes

Question 16

What is the mechanism of action for Thiazolidinediones

Answer 16

 PPAR-γ agonist. Agonistically bind to a nuclear hormone receptor site.
 Reduction in gluconeogenesis and an increased glucose uptake into muscles

Question 17

What are the adversereactions to the glitazones? (2)

Answer 17

 GI disturbance

 Weight gain

Question 18

What are the drug drug interactions of glitazones complicated by?

Answer 18

 Very heavily protein bound (~99%)

Question 19

Give two examples of meglitidines

Answer 19

 Repaglinide

 Nateglinide

Question 20

What are the indications for meglitidines

Answer 20

 Uncontrolled non insulin dependant diabetes

Question 21

What is the mechanism of action for meglitidine?

Answer 21

 K+/ATP channel antagonists on β-cells, resulting in depolarisation, calcium entry and fusion of insulin containing vesicles with membrane

Question 22

What concerning adverse drug reactions mean it is good to treat with meglitidines? (2)

Answer 22

 Relatively lower risk of hypoglycaemia than Sulphonylureas

 Not associated with weight gain – useful in treating obese patients

Question 23

Name four different types of insulins

Answer 23

Ultra Rapid
Short Acting
Intermediate
Intermediate/Long Acting

Question 24

What are indications for short acting/rapid insulins

Answer 24

Meals/Acute Hyperglycaemia

Question 25

What are indications for intermediate/long acting insulins

Answer 25

Basal Insulin/Overnight control

Question 26

Give two different insulin regimes

Answer 26

Pre-mixed inssulin

Intermediate/long acting insulin + Fast or short acting insulin

Question 27

What is involved in a pre-mixed insulin regime?

Answer 27

Pre-mixed insulin is given twice a day, with morning and evening meals.

Question 28

What is involved in an intermediate/long acting insulin + Fast or short acting insulin regime

Answer 28

Intermediate/long lasting insulin provides a basal level that extends overnight, fast or short acting insulin is injected with meals to provide an acute response. This gives a better level of glycaemic control.

Question 29

What are indications for insulin treatment?

Answer 29

Insulin dependent diabetes mellitus

Question 30

What is the mechanism of action of insulin?

Answer 30

Acts like endogenous insulin

Question 31

Give three adverse drug reactions to insulin

Answer 31

 Local reactions
 Hypoglycaemia (coma) (overdose)
 Rarely, immune resistance

Question 32

Outline the process of T2 diabetes treatment

Answer 32

o Begin with no pharmacological intervention, therapy starting with Diet, Exercise and Lifestyle changes
o A Biguanide (Metformin) started when necessary
o Over time if HbA1c levels go above 7%, a Sulphonylurea (e.g. Tolbutamide) is added to therapy
o Over time if HbA1c levels go about 7.5% a Thiazolidinedione (e.g. Rosiglitazone) may be added, or a newer hypoglycaemic, or start insulin therapy
o If on this regime if HbA1c levels go above 7.5%, doses will be titrated upwards to regain adequate glycaemic control

Question 33

How is insulin dosing determined

Answer 33

Blood glucose monitoring several times a day

Question 34

What is HbA1c?

Answer 34

Glucose in the blood will react with the terminal valine of the haemoglobin molecule to produce glycosylated haemoglobin (HbA1c). The percentage of HBA1c is a good indicator of how effective blood glucose control has been.
As RBCs normally spend ~3 months in the circulation the %HbA1c is related to the average blood glucose concentration over the preceding 2-3 months.
Poorly controlled diabetics can have a HbA1c value above 10%. In combination therapy, new medications are added at HbA1c values of 7 or 7.5% (see above).

Question 35

Give three anti-obesity agents

Answer 35

Orlistat
Sibutramine
Rimonabant

Question 36

What is the mechanism of action of Orlistat

Answer 36

 Gastric and pancreatic lipase inhibitor

 Reduces the conversion of up to 30% of dietary fat to fatty acids and glycerol

Question 37

What is the mechanism of action of Sibutramine

Answer 37

 Noradrenaline and serotonin re-uptake inhibitor

 Appetite suppression, increased thermogenesis

Question 38

What is the mechanism of action of Rimonabant

Answer 38

 Endocannabinoid antagonist

Question 39

What are adverse drug reactions of Orlistat

Answer 39

 Broad GI disturbances

 (Soft fatty stools, flatus, faecal discharge/incontinence)

Question 40

What are adverse drug reactions of sibutramine

Answer 40

 Increased heart rate and blood pressure

Question 41

What are adverse drug reactions of rimonabant

Answer 41

 Depression – currently withdrawn in the UK by NICE