Formulations of insulin Flashcards
how is insulin characterised
characterised by differences in:
1. onset- how quickly they act
2. peak- how quickly they achieve maximum impact
3. duration- how long they last
4. route of delivery- sc, inhaled, buccal, transdermal
what are the different types of insulin
- short acting/rapid acting- lispro, aspart
- intermediate acting- isophane
- long acting- insulin glargine, detemir
describe administration through a subcutaneous route
- inject through skin into loose subcutaneous tissue and rotate site
- aqueous solution or suspension
- drug enters capillaries via diffusion/filtration
- blood supply important (vasoconstrictor, exercise)
what does regular insulin form
forms hexamers
what are the properties of hexamers
- delayed onset of action
- longer duration of action
describe the properties of rapid acting insulin analogues
- lower tendency to form hexamers
- exist as monomers- 5.8kDa
- more rapid diffusion into capillaries
- faster onset of action
describe how insulin detemir is absorbed
- rapidly absorbed but then binds to albumin via the fatty acid
- slowly dissociates from this complex
describe the changing of the iso-electric point of an insulin molecule
- insulin is an acidic protein, and at normal pH it is in an ionised state and water soluble
- by changing or adding some amino acids, the iso-electric point can be shifted from pH=4 to pH= 7
- the resulting insulin is less water soluble at ph 7, so easily self aggregates and precipitates to form micro crystals, which act as an insulin depot preparation
- this principle is used for insulin glargine
how do continuous subcutaneous insulin infusion pumps work
- dosage instructions are entered into the pumps small computer and the appropriate amount of insulin is injected into the body in a calculated, controlled manner
when is the insulin pump the best choice
- fear of needles
- difficulty in managing highs and lows
- fear of hypoglycaemia, especially at night
- HBA1C outside of target range
- reduced hypoglycaemia awareness
- concerns about long term complications
- seeking more flexibility in everyday life
what are the advantages of insulin pumps
- bolus when required- better control
- fewer injections
- more flexible lifestyle
- possible reduction in total dose of insulin
- fewer hypos
what are the disadvantages of insulin pumps
- test blood glucose more frequently
- infection at insertion site
- scarring at site
- dose adjustment required for carbs eaten
what do pump insulin interactions lead to
-insulin adsorption due to contact with hydrophobic surfaces
- insulin aggregation due to elevated temperature and agitation of pump, influenced by type of insulin, solvent, concentration
- leads to: loss of biological activity and blockage of infusion set/leakage at infusion site and connectors
what occurs in the fibrillation process
insulin molecules mis-fold and attach to each other to form large molecular weight fibrils
describe the stability of rapid acting insulins
- rapid acting insulin analogues are relatively resistant to degradation at 37 degrees and in prolonged storage
- but, manufacturers still stress that insulin exposed to temperatures above 37 should be discarded and reservoirs routinely changed
