The Pharmacology of Insulin

Question 1

How is energy made in uncontrolled diabetics and why?

What is the risk of this?

Answer 1

Ketogenesis ➞ no insulin means glucose can’t enter cells so body starts making ketones for energy

Risk ➞ diabetic ketoacidosis due to huge amounts of ketone bodies, the H+ associated with the ketones produce a metabolic acidosis

Question 2

Describe the process of ketogenesis

Answer 2

Mitochondrial oxaloacetate is depleted resulting in Acetly CoA reacting with its self to form acetoacetate and 3-hydroxybutyrate

Question 3

Give 4 functions of insulin?

Answer 3

1. stimulates uptake of glucose into liver, muscle and adipose tissue
2. Inhibition of gluconeogenesis
3. Inhibits glycogenolysis
4. promotes uptake of fats

Question 4

Ideally, therapeutic infusion of insulin should minic what?

Answer 4

The normal production of insulin in the body.

Question 5

In a patient with type 1 diabetes, what is the target HbA1C?

What is HBA1C and why is it useful clinically?

Answer 5

< 48 mmol/mol

HbA1C is glycated protein, minor component of haemoglobin. The levels can tell us cumulative exposure to plasma glucose concentration over last 120 days (average RBC lifespan)

Most reliably demonstrate 8 week average glucose control

Question 6

Before meals, what is the target blood glucose?

Answer 6

4–7 mmol/litre

Question 7

What is the ideal blood glucose upon waking up?

Answer 7

5–7 mmol/litre

Question 8

From what 2 methods can insulin be produced?

Answer 8

1) Recombinant DNA technology
2) Animals (less commonly used)

Question 9

Recombinant DNA technology produces insulin based on what?

Answer 9

The human insulin amino acid sequence

Question 10

Recombinant DNA technology alters human insulin to improve the PK, what specificallly is altered?

Answer 10

The C-terminal of the B-chain is altered

Question 11

What are the 5 main insulin categories?

Answer 11

• Short acting
• Rapid acting
• Intermediate acting
• Long acting
• Very long acting

Question 12

What type of injection is used to administer insulin?

Answer 12

subcutaneous

Question 13

What influences the rate of insulin absorbtion?

Answer 13

Formulation of insulin

Question 14

Rapid acting insulin is highly ____ within plasma. Once in plasma, rapid acting insulin disfavours _____ formation.

Answer 14

soluble, hexamer

Question 15

State the following regarding rapid acting insulin

a) onset
b) peak
c) duration
d) when to be taken + purpose

Answer 15

a) 5-15mins
b) 30-90mins
c) 4-6 hours
d) just before eating for meal control/ acute hyperglycaemia

Question 16

Name 2 examples of rapid acting insulin

Answer 16

• lispro
• aspart
• glulisine

Question 17

Short acting insulin forms what when it enters the blood?

Answer 17

Forms hexamers in solution ➞ the dissociation of these hexamers is what determines the rate of absorbtion (normally very short)

Question 18

State the following regarding short acting insulin

a) onset
b) peak
c) duration
d) when to be taken + purpose

Answer 18

a) 30-60mins
b) 2-3 hours
c) 8-10 hours
d) 15-20mins before eating for meal control/ acute hyperglycaemia

Question 19

What does the duration of short acting insulin mean for number of injections

Answer 19

Duration 8 to 10 hours - therefore multiple injections needed throughout the day

Question 20

What is the formulation of Intermediate acting insulin and why?

Answer 20

Suspended in a solution of protein and zinc which slows the rate of absorbtion.

Question 21

State the following regarding intermediate acting insulin

a) onset
b) peak
b) duration
c) when to be taken + purpose

Answer 21

a) 2-4 hour onset
b) 4-8 hours
b) 12-20 hours
c) 30mins before food OR at bedtime to maintain basal insulin/ overnight control

Question 22

Give a example of intermediate acting insulin

Answer 22

Isophane insulin

Question 23

Upon entering the plasma, what happens to long and very long acting insulin?

Answer 23

Formulation favours lower solubility, oligomer formation or binding to albumin

Question 24

State the following regarding long and very long acting insulin

a) onset
b) peak
b) duration
c) Purpose

Answer 24

a) 2-6 hour onset
b) no obvious peak
c) upto 24 hours ➞ very long up to 50+ hours
d) maintain basal insulin/ overnight control

Question 25

Give a example of long and very long acting insulin

Answer 25

* glargine * detemir * degludec (very long)

Question 26

State the average t1/2 of insulin?

Answer 26

Approx 6mins

Question 27

Name the 2 most common ways in which insulin is administered?

Answer 27

1) Subcutaneous injection * Fine gauge needle (insulin pen) * creates a small depot at injection site 2) Insulin pump devices * Supply a continuous infusion subcut * Programmable to allow basal and bolus doses

Question 28

Name 3 insulin regimes and when each is reccomended by NICE

Answer 28

1) Basal-bolus regimen ➞ first choice for all new T1D patients 2) Mixed (biphasic) regimen ➞ if (1) is not possible 3) Continuous subcutaneous insulin infusion ➞ specific criteria

Question 29

Describe the basal-bolus insulin regimen

Answer 29

Basal insulin ➞ one or more separate daily injections of intermediate or long-acting insulin analogue Bolus injections ➞ multiple injections of rapid or short-acting insulin before meals

Question 30

What is important to consider with the basal-bolus regime?

Answer 30

Flexibility to tailor insulin therapy with the carbohydrate load of each meal

Question 31

Describe the mixed (biphasic) regimen

Answer 31

Usually two injections per day of short-acting insulin mixed with intermediate-acting insulin Insulin preparations may be mixed by the patient

Question 32

Describe the continuous subcutaneous insulin infusion

Answer 32

Insulin pump ➞ insulin storage reservoir via a subcut needle or cannula which allows regular/continuous amounts of insulin Usually a rapid-acting insulin analogue or short acting soluble insulin

Question 33

Who is the continuous subcutaneous insulin infusion offered too?

Answer 33

Only offered to adults who: Suffer disabling hypoglycaemia OR have high HbA1c conc (\>69 mmol/mol)

Question 34

Give 4 adverse effects of insulin

Answer 34

* Hypoglycaemia * Hyperglycaemia * Lipodystrophy * Painful injections * Insulin allergies

Question 35

Give 4 ways to minimise Insulin prescribing errors in diabetic patients

Answer 35

1) Primary care ➞ regular reviews + dicussions about changes in insulin prescriptions and ensure patient knows how to use new insulin safely 2) when insulin is prescribed, dispensed or administered, healthcare professionals should confirm correct identity of insulin products 3) Pharmacists should confirm patient is expecting to change to a new insulin and patients should be shown what is being dispensed to verify it is what they are expecting 4) Inpatients should have electronic patient records and electronic prescribing (shown to minimise prescribing error)