Describe the pharmacology of short acting insulin (actrapid).
In general candidates lacked a sufficient depth of knowledge for this commonly used drug. Some candidates confused actrapid with novo rapid. A structured approach (e.g. pharmaceutics, mode of action, pharmacokinetics, etc.) was expected.
No, actrapid (neutral human insulin) is not the same as Novorapid, otherwise known as insulin aspart (which has been modified to weaken its self-association behaviour and therefore increase the rate of its absorption from subcutaneous depots).
| Name | Neutral human insulin (Actrapid, Humulin) |
| Class | Pancreatic hormone analog |
| Chemistry | Peptide hormone: Two chains, B (30 amino acids) and A (21 amino acids), with amino acids labelled by chain letter and number. |
| Routes of administration | IV or subcutaneously |
| Absorption | Essenially zero oral bioavailability. Absorbed from subcutaneous depot: onset of clinical effect is within about 30-60 min |
| Solubility | In low concentrations, present in monomeric form and is highly soluble. In high concentrations, undergoes oligomerisation, and becomes insoluble, with a pKA of 5.4 |
| Distribution | VOD= 0.44 L/kg; minimally protein-bound |
| Target receptor | Insulin receptor, a transmembrane receptor with an intracellular tyrosine kinase domai, which uses the PI3K secondary messenger pathway for intracellular signalling |
| Metabolism | Over 50% metabolism by the liver, 30% by the proximal tubule in the kdiney, the rest by skeletal muscle and adipose tissue. Ligand/receptor complex is endocytosed and degraded after it binds its receptor. |
| Elimination | Only 1% of the free drug is eliminated in the kidney |
| Time course of action | Onset of effect = 30-60 min, peak activity at 2-3 hrs, duration of action apporoximately 6-10 hrs |
| Mechanism of action | Increases the exocytosis and cell surface expression of GLUT4 transport proteins, which results in the uptake of glucose into insulin-sensitive tissues. Also multiple metabolic effects: decreased glycogenolysis and increased glycogen synthesis in the liver, decreased free fatty acid mobilisation by fatty tissue, increased lipoprotein lipase activity, decreased protein catabolism, positive inotrpic effects, and decreased releae of glucagon |
| Clinical effects | - Increased glucose uptake into liver, skeletal muscle, adipose tissue - decreased hepatic glycogenolysis - increased hepatic glycogen synthesis - decreased free fatty acid mobilisation by fatty tissue - increased lipoprotein lipase activity - decreased protein catabolism - positive inotropic effects - decreased release of glucagon |
| Single best reference for further information | Owens, 1986 |