Insulin Therapy - Properties And Products W3 Flashcards
Chemical structre of insulin
- 2x peptide chains
- chain A = 21 amino.a.residues
- chain B = 30 amino.a.residues
- chains linked by disulphide bridges between A7+B7 and A20+B19
- chain A is also internally bridges between A6+A11
Bovine insulin
derived from cows and has three amino acid differences from human insulin, making it more likely to cause immune reactions when administered.
Porcine insulin
Animal derived - pork
No longer avaliabe as causes allergic reactions
Secondary structure of insulin
- alpha helix
- three segments
- intra-molecular H-bonding between amide groups
Tertiary structure of insulin
- disulphide bridges
Quaternary structure of insulin - dimer
- in solution, exists as dimers
- anti-parallel b sheet formed between B23 and B30, with B28 proline which is important in hydrophobic interactions
- stabilised by H-bonding involving B24 and B26
Quaternary structure of insulin - hexamer
- two zinc ions and three insulin dimers
- globular
- interior is mainly non-polar amino acid side chains
- exterior is mainly polar amino acid side chains
- T (extended B1 to B8) and R (a-helix B1 to B8) confirmations
- R state found in presence of phenol or cresol
- R state more stable
Physical properties of insulin
• White to almost white powder
• Can be amorphous or crystalline
• Practically insoluble in water, in ethanol and in ether
• Dissolves in dilute mineral acids
• Dissolves with decomposition in dilute solutions of alkali hydroxides
porcine and bovine
animal-derived insulin
Porcine insulin is derived from the pancreas of pigs. The insulin produced by pigs is structurally similar to human insulin, with only one amino acid difference in the B-chain
Bovine insulin is derived from cows and differs from human insulin more significantly than porcine insulin. The amino acid sequence of bovine insulin differs at three positions in the B-chain
semi synthetic human insulin
Chemically identical to human insulin
produced by modifying biosynthetic human insulin
biosynthetic human insulin
Chemically identical to human insulin
produced through recombinant DNA technology
Expression of strength
• Use “International Units” (IU)
• One unit = 0.0345 mg porcine insulin
= 0.0342 mg bovine insulin
= 0.0347 mg human insulin
General points of injectable insulin
Insulin is a protein
- unstable in GI tract
Generally given by sc injection
- occasionally im
- iv in emergencies
Injection sites
- thighs, upper arms, buttocks, abdominal wall
- need to rotate sites
- Absorption faster from abdominal wall
- Exercise and heat will increase rate of absorption
Insulin Injectable Formulations - soluble
Also called “neutral insulin”
most commonly used
clear, fast-acting
Insulin Injectable Formulations - zinc susp
intermediate-acting insulin
Zinc helps to slow the absorption of insulin after injection, making it act more slowly than regular insulin
Insulin Injectable Formulations - isophane
most commonly used forms of intermediate-acting insulin. It’s a suspension of insulin that’s modified with protamine (a protein) and zinc
slowly releasing insulin over a longer period of time
Insulin Injectable Formulations - protamine zinc
long-acting insulin formulation
combines insulin, protamine (a protein), and zinc to slow the release and absorption of insulin, making it effective for basal insulin coverage
Insulin Injectable Formulations - biphasic isophane
combination of intermediate-acting insulin and short-acting insulin
It is formulated to provide both basal and prandial (meal-time) insulin coverage in a single injection,
Biological importance of physico-chemical properties
- Insulin molecules need to be in solution and in monomer form for biological action
- Physical state will affect dissolution from solid into solution
- amorphous - act faster than the crystalline form
- size of the crystals affect the dissolution rate
- Presence of additives affect the dissolution rate
- zinc+protamine reduces the dissolution rate
Onset of action, peak action and duration of action - soluble
onset = 30-60mins
peak = 2-4hrs
DOA = 8hrs
New human insulin analogues
Insulin Aspart (NovoLog)
Brand: NovoLog (Novo Nordisk)
Onset: 10-20 minutes after injection
Peak Effect: 1-3 hours
Duration: 3-5 hours
insulin aspart
- rapid-acting analogue
- slightly faster onset than regular insulin.
- is modified by substituting one amino acid = reduces the tendency to form hexamers = increasing the rate which it enters the bloodstream.
