The Pharmacology of Insulin Flashcards
How is energy made in uncontrolled diabetics and why?
What is the risk of this?
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
Describe the process of ketogenesis
Mitochondrial oxaloacetate is depleted resulting in Acetly CoA reacting with its self to form acetoacetate and 3-hydroxybutyrate
Give 4 functions of insulin?
- stimulates uptake of glucose into liver, muscle and adipose tissue
- Inhibition of gluconeogenesis
- Inhibits glycogenolysis
- promotes uptake of fats
Ideally, therapeutic infusion of insulin should minic what?
The normal production of insulin in the body.
In a patient with type 1 diabetes, what is the target HbA1C?
What is HBA1C and why is it useful clinically?
< 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
Before meals, what is the target blood glucose?
4–7 mmol/litre
What is the ideal blood glucose upon waking up?
5–7 mmol/litre
From what 2 methods can insulin be produced?
1) Recombinant DNA technology
2) Animals (less commonly used)
Recombinant DNA technology produces insulin based on what?
The human insulin amino acid sequence
Recombinant DNA technology alters human insulin to improve the PK, what specificallly is altered?
The C-terminal of the B-chain is altered
What are the 5 main insulin categories?
- Short acting
- Rapid acting
- Intermediate acting
- Long acting
- Very long acting
What type of injection is used to administer insulin?
subcutaneous
What influences the rate of insulin absorbtion?
Formulation of insulin
Rapid acting insulin is highly ____ within plasma. Once in plasma, rapid acting insulin disfavours _____ formation.
soluble, hexamer
State the following regarding rapid acting insulin
a) onset
b) peak
c) duration
d) when to be taken + purpose
a) 5-15mins
b) 30-90mins
c) 4-6 hours
d) just before eating for meal control/ acute hyperglycaemia
Name 2 examples of rapid acting insulin
- lispro
- aspart
- glulisine
Short acting insulin forms what when it enters the blood?
Forms hexamers in solution ➞ the dissociation of these hexamers is what determines the rate of absorbtion (normally very short)
State the following regarding short acting insulin
a) onset
b) peak
c) duration
d) when to be taken + purpose
a) 30-60mins
b) 2-3 hours
c) 8-10 hours
d) 15-20mins before eating for meal control/ acute hyperglycaemia
What does the duration of short acting insulin mean for number of injections
Duration 8 to 10 hours - therefore multiple injections needed throughout the day
What is the formulation of Intermediate acting insulin and why?
Suspended in a solution of protein and zinc which slows the rate of absorbtion.
State the following regarding intermediate acting insulin
a) onset
b) peak
b) duration
c) when to be taken + purpose
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
Give a example of intermediate acting insulin
Isophane insulin
Upon entering the plasma, what happens to long and very long acting insulin?
Formulation favours lower solubility, oligomer formation or binding to albumin
State the following regarding long and very long acting insulin
a) onset
b) peak
b) duration
c) Purpose
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
Give a example of long and very long acting insulin
- glargine
- detemir
- degludec (very long)
State the average t1/2 of insulin?
Approx 6mins
Name the 2 most common ways in which insulin is administered?
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
Name 3 insulin regimes and when each is reccomended by NICE
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
Describe the basal-bolus insulin regimen
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
What is important to consider with the basal-bolus regime?
Flexibility to tailor insulin therapy with the carbohydrate load of each meal
Describe the mixed (biphasic) regimen
Usually two injections per day of short-acting insulin mixed with intermediate-acting insulin
Insulin preparations may be mixed by the patient
Describe the continuous subcutaneous insulin infusion
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
Who is the continuous subcutaneous insulin infusion offered too?
Only offered to adults who:
Suffer disabling hypoglycaemia OR have high HbA1c conc (>69 mmol/mol)
Give 4 adverse effects of insulin
- Hypoglycaemia
- Hyperglycaemia
- Lipodystrophy
- Painful injections
- Insulin allergies
Give 4 ways to minimise Insulin prescribing errors in diabetic patients
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)
