1. Insulin preparations: classification (by origin and duration of action), relationship between pharmacokinetic properties and timing of administration.
Insulin isolated from beef & pork pancreas (Pork insulin closest in structure to human insulin, differing only one amino acid). However, human insulin replacing animal hormone for therapy. Human insulin produced by special strain of E coli genetically altered contain gene for human insulin.
A. Rapid action insulin preparations
This category contains 4 preparations:
- regular insulin - insulin lispro - insulin aspart - insulin glulisin
Regular insulin is short-acting soluble crystalline zinc insulin. Usually given subcutaneously (or intravenously in emergencies) & lowers blood sugar within minutes. It is the only insulin preparation suitable for intravenous administration. Both human recombinant & animal source insulin available in this form. The other 3 types classified as ultrashort-acting insulin because of rapid onset & short duration of action.
Lispro insulin differs from regular in that lysine & proline at positions 28 & 29 in B chain reversed, results in more rapid absorption after subcutaneous injections than with regular, as consequence lispro acts more rapidly & has shorter duration of activity. Aspart & glulisin have similar pharmacokinetics & pharmacodynamics as lispro.
Those preparations administrated subcutaneously to mimic prandial release of insulin & usually used with long acting insulin to assure proper glucose control.
B. Intermediate action insulin preparations
1. Lente insulin - amorphous precipitate of insulin with zinc ion in acetate buffer combined with 70% ultralente insulin. Onset of action & peak effect somewhat slower than of regular, but sustained for longer period. 2. NPH (neutral protamine Hagedorn) insulin - suspension of crystalline zinc insulin combined at neutral pH with protamine. Duration of action - intermediate, due to delayed absorption because conjugation with protamine forms less soluble complex. NPH should only be given subcutaneously & useful in treating all forms of diabetes except diabetic ketoacidosis or emergency hyperglycemia. Usually given along with regular insulin.
C. Prolonged action insulin preparations
1. Ultralente insulin (extended zinc insulin) - suspension zinc insulin crystals in acetate buffer. Produces large particles which slow to dissolve, producing slow onset of action & long lasting hypoglycemic effect. 2. Insulin glargine - isoelectric point of that insulin lower than that of human insulin, leading to precipitation in injection site, thereby extending its action. Actually has flat, prolonged hypoglycemic effect meaning - has no peak. Must be given subcutaneously.
D. Insulin combinations Various combinations of human insulins, such as [70% NPH insulin + 30% regular insulin] also available.
Insulin preparations which act more rapidly, but have short duration used to control glucose level after meals, be administrated around time of food intake. Preparation having low peak but long duration used to prevent catabolic effect of insulin insufficiency, be administrated regularly without dependence on meals timing.
2. Short-acting insulin preparations.
- regular insulin - insulin lispro - insulin aspart - insulin glulisin
Regular - short acting soluble crystalline zinc insulin. Usually given subcutaneously (intravenously in emergencies) & rapidly lowers blood glucose. Safely used during pregnancy whereas other 3 advised during pregnancy only if clearly needed.
Other 3 types classified as ultrashort-acting insulin because rapid onset & short duration of action. These offer more flexible treatment regimens & lower risk of hypoglycemia. Lispro insulin differs from regular in that lysine & proline at positions 28 & 29 in B chain reversed, results in more rapid absorption after subcutaneous injections than with regular, as consequence lispro acts more rapidly & has shorter duration of activity.
