INSULIN THERAPY PREPARATIONS AND CLINICAL USE

Insulin

preparations differ mainly in their rate of absorption after subcutaneous injection. The rapidly absorbed and short-acting regular insulin is the only preparation that can be given intravenousl y and also in pregnancy.

All insulin preparations are available in strengths of 40 and 100 units/ml. Most insulins are administered two or three times dail y often, in combinations of regular and intermediate-acting forms. MECHANISM OF ACTION

Insulin

acts by binding to specific receptors on the surface of insulin-sensitive tissue. The receptor is composed four functional subunits, two alpha and two beta. The alpha subunit binds insulin, whereas the beta subunit is a tyrosine-specific kinase.

Stimulation of the receptor by insulin causes phosphorylation of the beta subunit and endogenous substrates, initiating a number biochemical events (e.g., facilitation of glucose transport into cells, enhancement of amino acid incorporation into proteins, increase d lipid synthesis).

INSULIN PREPARATIONS

 Portable pen injection Continuous subcutaneous insulin infusion devices (CSII, insulin pumps) Inhaled insulin

Preparations of insulin

Injection pen

DOSAGE The normal pancreas produces from 30 to 50 units of insulin per day, so most diabetics with insulin deficienc y require some what less than this dosage of insulin. Usual nonpregnant adults theoreticall y require 0.6 units/kg of insulin every 24 h. ADVERSE REACTIONS Hypogl ycemia is the major adverse reaction of insulin therapy. Warning s ymptoms of milder degrees of hypoglycemia such as fatigue, headache, and drowsiness must be watched. H ypoglycemia can be anticipated to occur at the time of peak action of the insulin.

A severe prolong hypoglycemic reaction can, if untreated, lead to permanent cerebral damage, coma, or death. The prime clinical

manifestations of insulin over-dosage are due to the effects of hypogl ycemia on the nervous system. Allergic reactions to insulin can be either local or systemic. Local allergic reactions include the formation of an erythematous area at the site of injection. This reactions appears within an hour and ma y persist for several days;

It usuall y occurs within the first few da ys after initiation or reinstitution of insulin therapy, suggesting prior sensitization to beef or pork protein. Systemic allergy consists of angioedema, nausea, vomiting, diarrhea, bronchial asthma, and dyspnea. H ypotension, shock, and death are also produced occasionall y. Systemic manifestations from therapeutic doses of insulin usually occurs in patients having a history of allergic reactions to other drugs or those being treated with insulin intermittentl y. To reduce the incidence of allergic reactions, it ma y be necessary to change to an insulin from a different source or to human insulin.

Adverse reactions attributable directl y to insulin administration are due to two factors; (i) Impurities in insulin preparations and (ii) Species of origin. These two factors are particularl y important with respect to insulin allergenicit y. Highly purified insulins are far less antigenic than impure insulins, and human insulins is less antigenic than porcine, which in turn is less antigenic than bovine. INSULIN COMBINATIONS

Various premixed combinations of human insulins, are also available. THANKS