Insulin, therapeutic uses
The main indication of insulin is type I diabetes mellitus, diabetes mellitus of the pregnant women, diabetic ketoacetosis. It can be used, often in combination with metformin, for the treatment certain noninsulin-dependant diabetes.
The dosage is adapted according to the results of glycemia and glycosuria, reflecting the immediate effect of insulin, and of glycosylated hemoglobin, reflecting its long-term effects.
Presentations
Insulin used in therapeutics was initially extracted from the pancreas, either of pork or beef. Insulin from pork differs from human insulin by one amino acid, insulin of ox by three amino acids.
Initially, one sought an increasingly pushed purification of insulin of animal origin, purification obtained by chromatography, which made it possible to obtain insulins called “mono peak” or “mono-compound”.
Later, animal insulin was replaced by human insulin obtained, either by the transformation of pig insulin by chemical processing, or by bacterial synthesis by recombinant DNA technique. The benefit in having pure human insulin is to decrease the risk of antibody formation.
Currently all insulins are of biogenetic origin.
Now, one distinguishes human insulins and their analogues like insulin lispro, insulin aspart, insulin glargine which differ from it by certain amino acids and have different kinetics of action.
The duration of action of insulin after subcutaneous injection can be sustained when the preparation contains protamine or zinc, obtaining long acting insulins.
Insulin lispro, is different from human insulin by an inversion of the position of two amino acids, lysin and praline on chain B, hence the term lispro. Insulin aspart is also an analog of human insulin where a proline is replaced by an aspartic acid. Insulins lispro and aspart have an effect of faster outbreak and shorter duration than regular human insulin, primarily because of faster absorption from the point of subcutaneous injection. Insulin glargine is obtained by addition of 2 arginine molecules to the chain B of insulin and substitution of asparagine by glycine in position 21 of chain A. Insuline glargine has a sustained and constant action, over approximately 24 hours, called without peak as opposed to other insulins. It is administered only once a day, the injection being made at the same time each day.
In practice, insulins are classified according to their duration of action after subcutaneous injection as very short- and short-, intermediate- and long-acting. In addition one distinguishes various presentations, insulins for syringe, jet injector system and pump.
All insulin presentations contain 100 units/mL.
Each pharmaceutical laboratory marketing insulin proposes a whole range of formulations:
- Insulins Aventis, Insuman *, insulins Lantus *,.
- Insulins Novo, Nordisk, Actrapid *, Insulatard, Mixtard * and Ultratard .
- Insulins Lilly, Umuline * and analogues of insulin, insulin lispro *, Humalog *.
- Novo insulins: insulins aspart, Novomix *, Velosulin *, Novorapid *
Administration
Insulin, inactive by oral route, is administered by parenteral route: intravenous for injectable solution used in hyperglycemic coma, and usually subcutaneous for injectable suspension.
The aim of the treatment is to combine the administrations of insulin with duration of different action (rapid-acting, intermediate, slow insulin) to obtain plasma concentrations close to the physiological plasma insulin level without however multiplying the number of injections.
The patients themselves administer their insulin by subcutaneous route. They use three types of insulins, according to their kinetics of action,: fast and short action (duration 5 to 8 h.), intermediate action (duration 12 to 18 h.) and sustained action (duration approximately 24 h.). The combined use of these insulin types tends to obtain plasma insulin levels approaching the course of physiological levels.
The administration of insulin by pumps at programmable injection rates is possible. The administration by nasal route was also proposed. Moreover insulin production by grafts of beta cells is currently considered.
Ongoing studies make it possible to administer insulin by nasal, bronchial and even oral routes.
Adverse effects
Insulin can cause various adverse effects:
- Hypoglycemia resulting in a feeling of hunger, sweats, muscular exhaustion, neuropsychic disorders, coma in the event of overdose. Hypoglycemia can be corrected by sugar intake by oral route or if necessary by intravenous perfusion, or by the injection of an hyperglycaemic drug such as glucagon or diazoxide if there is no glucose to hand.
- Insulin resistance requiring an increase in dosage.
- Local reactions with insulin injections: pruritus, induration, atrophy or hypertrophy of adipose tissues.
- Decrease of plasma potassium.
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