Side effects of insulin therapy. Insulin "Detemir": instructions for use, composition, action and analogues Local manifestations and hypersensitivity, intolerance

However, reports of insulin allergy and insulin resistance to all new types of insulin (human and analogues) continue to be received1. The manifestations of immune reactions to human insulin and its analogues (short and long-acting) do not differ, since modification of the human insulin molecule does not affect its immunogenic sites.
Despite the relatively high frequency of detection of autoantibodies to insulin in T1DM, the frequency of immune complications of insulin therapy in T1DM and T2DM is practically the same.
If you study inflammatory reactions at the injection site of modern insulins with passion and daily, then in the first 2-4 weeks of treatment they can be noted in 1-2% of cases, which spontaneously disappear over the next 1-2 months in 90% of patients, and in the rest 5% of patients - within 6-12 months. There are three types of local allergic reactions and a systemic reaction to insulin preparations, and the symptoms of allergy to new insulin preparations remain the same as before to animals:

local immediate inflammatory with blistering rashes: within the next 30 minutes after administration, an inflammatory reaction appears at the injection site, which may be accompanied by pain, itching and blisters and disappears within an hour. This reaction may be accompanied by repeated development of inflammatory phenomena (pain, erythema) at the injection site with a peak after 12-24 hours (biphasic reaction);
Arthus phenomenon (reaction to the accumulation of antigen-antibody complexes at the site of insulin administration): moderately severe inflammation at the site of insulin administration after 4-6 hours with a peak after 12 hours and is characterized by local damage to small vessels and a neutrophilic infiltrate. It is observed very rarely;
local delayed inflammatory reaction (tuberculin type): develops 8-12 hours after administration with a peak after 24 hours. At the injection site, an inflammatory reaction occurs with clear boundaries and usually involves subcutaneous fat, which is painful and often accompanied by itching and pain. Histologically, a perivascular accumulation of mononucleocytes is detected;
systemic allergy: in the immediate minutes after insulin administration, urticaria, angioedema, anaphylaxis and other systemic reactions develop, which are usually accompanied by an immediate local reaction.

At the same time, overdiagnosis of insulin allergy, especially the immediate type, as clinical experience shows, is quite common - approximately one patient every six months is admitted to our clinic with a diagnosis of insulin allergy, which served as a reason for refusing insulin therapy. Although the differential diagnosis of an allergy to an insulin drug from an allergy of another origin is not difficult, since it has characteristic distinctive features (specific symptoms). My analysis of allergic reactions1 to insulin preparations over more than 50 years of insulin therapy practice showed that an immediate systemic allergic reaction to insulin (such as urticaria, etc.) does not occur without manifestations of allergies at the site of drug administration (itching, redness, blistering rashes and so on.). It develops no earlier than 1-2 weeks from the start of insulin therapy, when the content of IgE antibodies to insulin (reagins) in the blood increases sufficiently, which are not blocked in some patients by a friendly, but insufficient growth of antibodies of the IgM and IgG1 class. But if doubts about the diagnosis of allergy remain, then a regular intradermal test should be performed with an insulin preparation that is considered allergenic for the patient, and for this there is no need to dilute the insulin, since anaphylactic reactions do not occur even in doubtful cases. In the case of an allergy to immediate-type insulin, itching, redness, a blister, sometimes with pseudopodia, etc. appear at the site of intradermal injection of insulin after about 20 minutes. An immediate allergy test is considered positive when a blister appears at the intradermal injection site measuring more than 5 mm, and the reaction is considered severe when the blister is larger than 1 cm. To exclude all types of local allergic reactions, the site of intradermal insulin injection should be observed for the first 20 minutes after injection, after 6 hours and after 24 hours. If an allergy is confirmed, then testing is carried out with other insulin preparations and the least allergenic one for the patient is selected for continued treatment. If there is no such insulin and the local reaction is pronounced, then reduce the dose of insulin administered to one site: divide the required dose into several injection sites or prescribe treatment with an insulin dispenser. It is recommended to add dexamethasone to the insulin bottle (1-2 mg of dexamethasone per 1000 units/bottle). Systemic antihistamines are prescribed. You can, for example, prepare an ex tempore solution of insulin with 0.1 ml of 1% diphenhydramine and inject it subcutaneously with good results. Unlike pipolfen, it did not cause turbidity in the insulin solution. In case of a pronounced local immediate reaction, intradermal hyposensitization also helps. These treatments are usually temporary, as the local insulin allergy disappears over the coming months with continued insulin treatment.
If a systemic allergic reaction to insulin is confirmed by intradermal testing, intradermal hyposensitization with insulin is performed, which can take from several days to months, unless there is an urgent need to administer a full dose of insulin (diabetic coma or severe decompensation of diabetes, fraught with rapid development of diabetic coma). Many methods of intradermal hyposensitization with insulin (in fact, immunization with insulin) have been proposed, largely differing in the rate of increase in the intradermal dose of insulin. The rate of hyposensitization in the case of severe allergic reactions of the immediate type is determined primarily by the body's reaction to an increase in the dose of insulin. Sometimes it is suggested to start with very high, almost homeopathic, dilutions (1:100,000, for example). Hyposensitization techniques, which are still used today in the treatment of allergies to human insulin preparations and human insulin analogues, have been described a long time ago, including in my doctoral dissertation, which presents the results of treatment of about 50 cases of severe immediate allergic reaction to all insulin preparations produced at that time. Treatment is extremely burdensome for both the patient and the doctor, sometimes dragging on for several months. But ultimately, it is possible to relieve any patient who seeks help from severe systemic allergy to insulin.
And, finally, how to treat an allergy to insulin if it occurs in response to all insulin preparations, and the patient urgently needs insulin for health reasons? If the patient is in a diabetic coma or precoma, then insulin is prescribed in the dose necessary for removal from the coma, even intravenously, without any prior hyposensitization or administration of antihistamines or glucocorticoids. In the world practice of insulin therapy, four such cases have been described, in two of which insulin therapy was carried out despite allergies, and the patients were brought out of a coma, and they did not develop an anaphylactic reaction, despite intravenous administration of insulin. In two other cases, when doctors refrained from administering insulin in a timely manner, the patients died from a diabetic coma.

(module direct4)

Suspicion of an allergy to a human insulin preparation or an analogue of human insulin in patients admitted to our clinic has not yet been confirmed in any case (including intradermal testing), and the patients were prescribed the necessary insulin preparation without any allergic consequences.
Immune insulin resistance to modern insulin preparations, which is caused by IgM and IgG antibodies to insulin, is extremely rare, and therefore pseudo-insulin resistance must first be excluded. In non-obese patients, a sign of moderate insulin resistance is the need for insulin 1-2 units/kg of body weight, and severe - more than 2 units/kg. If the insulin prescribed to the patient does not have the expected hypoglycemic effect, then you first need to check:

serviceability of the insulin pen;
adequacy of the insulin syringe markings to the insulin concentration in the vial;
adequacy of the cartridge with the insulin pen;
the expiration date of the administered insulin, and if the period is appropriate, then still change the cartridge (bottle) to a new one;
personally control the method of administering insulin to patients;
exclude diseases that increase the need for insulin, mainly inflammatory and oncological diseases (lymphoma).

If all the possible reasons described above are excluded, then instruct only the guard nurse to administer insulin. If all these measures do not improve the results of treatment, then we can assume that the patient has true immune insulin resistance. Usually it disappears within a year, rarely 5 years, without any treatment.
It is advisable to confirm the diagnosis of immune insulin resistance by testing antibodies to insulin, which, unfortunately, is not routine. Treatment begins with changing the type of insulin - from human to an analogue of human insulin or vice versa, depending on what treatment the patient was on. If changing the type of insulin does not help, immunosuppressive therapy with glucocorticoids is prescribed. In 50% of patients, high doses of glucocorticoids are effective (starting dose of prednisolone is 40-80 mg), treatment of which is carried out for 2-4 weeks. Hospitalization for treatment of immune insulin resistance is mandatory because there may be a dramatic decrease in insulin requirements requiring immediate correction.
If immune insulin resistance is rare, then in T2DM, a decrease in sensitivity to the biological action of insulin (“biological” insulin resistance) is its integral feature. However, it is quite difficult to prove this biological insulin resistance in patients with T2DM using a clinically acceptable method. As stated above, insulin resistance is assessed today by its requirement per 1 kg of body weight. Taking into account the fact that the vast majority of patients with T2DM are obese, the calculation of insulin per 1 kg of their increased body weight usually fits into “normal” insulin sensitivity. Whether insulin sensitivity should be assessed in relation to ideal body weight in obese patients is silent. Most likely not, since adipose tissue is insulin-dependent and requires a certain proportion of secreted insulin to maintain its function. From a therapeutic point of view, the question of the diagnostic criterion for insulin resistance in patients with T2DM is irrelevant until they are suspected of having immune insulin resistance to an insulin drug. Probably, in patients with T2DM, you can use the old criterion of insulin resistance - a daily dose of insulin of more than 200 units, which may be a reason for differential diagnosis of immune and biological insulin resistance, at least according to such an indirect criterion in this case as antibodies to insulin in the patient’s blood serum . It should be noted that the criterion of insulin resistance of 200 units/day was introduced as a result of erroneous reasoning. In early experimental studies on dogs, it was found that their daily insulin secretion does not exceed 60 units. Having calculated the dog's insulin requirement per 1 kg of its body weight, the researchers, taking into account the average human body weight, concluded that a person normally secretes 200 units. insulin per day. Subsequently, it was found that in humans, daily insulin secretion does not exceed 60 units, but clinicians never abandoned the criterion of insulin resistance of 200 units/day.
The development of lipoatrophy (disappearance of subcutaneous fat) at the site of insulin administration is also associated with antibodies to insulin, which are mainly IgG and IgM and block the biological effect of insulin. These antibodies, accumulating at the injection site of the insulin drug in high concentrations (due to the high concentration of insulin antigen at the injection site), begin to compete with insulin receptors on adipocytes. As a result, the lipogenic effect of insulin at the injection site is blocked and fat disappears from the subcutaneous fat. This was indirectly proven during an immunological examination of children with diabetes and lipoatrophy at the site of insulin administration - their antibody titer to insulin simply went off scale. Based on the above, the effectiveness of changing the type of insulin from a porcine insulin preparation to a human insulin preparation in the treatment of lipoatrophy is clear: the antibodies produced by porcine insulin did not interact with human insulin and their insulin-blocking effect on adipocytes was removed.
Currently, lipoatrophy at insulin injection sites is not observed, but if they did occur, it would probably be effective to replace human insulin with human insulin analogues, and vice versa, depending on which insulin lipoatrophy developed.
However, the problem of local reactions to the insulin drug has not disappeared. The so-called lipohypertrophy is still observed and is associated not with hypertrophy of adipocytes, as the name would seem to suggest, but with the development of scar tissue at the site of subcutaneous injection, with a soft-elastic consistency that imitates local hypertrophy of subcutaneous adipose tissue. The genesis of this adverse reaction is unclear, as is the genesis of any keloid, but the mechanism is likely traumatic, since these sites occur primarily in individuals who rarely change the insulin injection site and injection needle (it must be thrown away after each injection!). Therefore, the recommendations are obvious - to avoid injecting insulin into the lipohypertrophic area, especially since the absorption of insulin from it turns out to be reduced and unpredictable. It is imperative to change each time the injection site and needle for administering insulin, with which patients must be provided in sufficient quantities.
And finally, the most difficult to differentiate are nonspecific inflammatory reactions at the site of insulin injection, which usually manifest themselves as compactions in the subcutaneous fat, appearing the day after the injection and slowly dissolving over days or weeks. Previously, all of them were usually classified as delayed-type allergic reactions1, but taking into account the high purity of insulin preparations, they are no longer considered as such. They can be characterized by such a rather vague term as “irritation”, or a more professional one - “inflammation” - at the site of insulin administration. Perhaps we can indicate the two most common causes of these local reactions. First of all, this is the administration of a cold insulin preparation, removed from the refrigerator immediately before the injection. The patient should be reminded that vials (insulin pen with cartridge) used for insulin therapy should be stored at room temperature. The quality of the insulin preparation will not be affected, especially if you adhere to the general rule that the bottle (cartridge) is used for no more than a month and thrown away after this period, even if there is insulin left in it.
Another reason for local inflammatory reactions is associated with the “acidity” of the insulin drug. The first insulin preparations were “acidic” in composition, since only in such an environment does insulin not crystallize. However, acidic solutions cause tissue damage and, accordingly, inflammatory reactions at the injection site. Chemists spent a lot of effort to prepare “non-acidic”, so-called “neutral”, insulin preparations in which it remained completely dissolved. And almost (!) all modern insulin preparations are neutral, with the exception of the drug Lantus, in which prolongation is ensured precisely by the crystallization of insulin. Because of this, local inflammatory reactions develop in response to its administration more often than to other drugs. The treatment method is to inject insulin into the deep layers of subcutaneous fat so that inflammation does not appear on the skin, which is the greatest concern. These reactions do not affect the effect of treatment and do not become a reason for changing the drug, i.e. reactions are expressed quite moderately.
We conducted a special study aimed at clarifying the harm of irregularly changing the insulin needle after each insulin injection, and found that discomfort during and at the site of insulin injection occurs more often, the less often the injection needle is changed.
Which is no coincidence, given the nature of the change in the needle when it is reused. It should be noted that the manufacturer has developed a special technology for the production of atraumatic insulin needles. However, after the first injection, the needle loses its atraumatic properties, and with frequent use it becomes completely unsuitable.
Infection of the needle became more common the less often it was changed. But in some patients the needle became infected after the first injection.
A completely new, previously unheard-of side effect of insulin therapy, induced by new technologies for the production of insulin preparations, has become mass insulinophobia - a fear of treatment with certain insulin preparations, widespread among the general population. An example is refusal of treatment with pork insulin for religious reasons. At one time, mainly in the USA, a campaign was launched against genetically engineered insulins as part of a protest against genetically engineered products in principle.

Protein-peptide hormonal drug; Insulin is used as a specific treatment for diabetes mellitus.

Insulin actively affects carbohydrate metabolism - it helps to reduce the content in the blood and its absorption by tissues, facilitates the penetration of glucose into cells, promotes the synthesis of glycogen, and prevents the conversion of fats and amino acids into carbohydrates.

Indications for use

Diabetes.

In small doses (5–10 units) insulin is used for liver diseases (hepatitis, initial stages of cirrhosis), acidosis, exhaustion, loss of nutrition, furunculosis, and thyrotoxicosis.

In neuropsychiatric practice, insulin is used for alcoholism and depletion of the nervous system (in doses that cause a hypoglycemic state).

In psychiatry - for insulin comatose therapy (in the treatment of some forms of schizophrenia, insulin solution is administered in significant quantities, which, with a gradual increase in doses, cause hypoglycemic shock).

In dermatology, insulin is used for diabetic toxiderma, as a nonspecific remedy for eczema, acne, urticaria, psoriasis, chronic pyoderma and yeast skin lesions.

Rules of application

Typically, insulin is administered subcutaneously or intramuscularly, intravenously - only in particularly severe cases of diabetic coma; suspended drugs are administered only subcutaneously.

Injections of the daily dose are made in 2-3 doses, half an hour to an hour before meals, the effect of a single dose of the drug begins after 30-60 minutes and lasts 4-8 hours.

With intravenous administration of insulin, the maximum hypoglycemic effect is achieved after 20–30 minutes, and the sugar level returns to its original level after 1–2 hours.

Before drawing suspensions of long-acting insulin preparations into a syringe, the contents should be shaken until a uniform suspension is formed in the bottle.

At diabetes mellitus treatment is carried out subject to simultaneous adherence to a diet; the dosage is set depending on the severity of the disease, the patient’s condition and the sugar content in the urine (at the rate of 1 unit for every 5 g of sugar excreted in the urine). Typically, insulin doses range from 10 to 40 units per day.

At diabetic coma the daily dose of the drug administered subcutaneously can be increased to 100 units or more, and when administered intravenously - up to 50 units per day.

At diabetic toxicoderma Insulin is prescribed in large doses, the amount of which depends on the severity of the underlying disease.

For other indications, small doses of insulin are usually prescribed (6–10 units per day), often (for general exhaustion, liver disease) in combination with a glucose load.

Side effects

With an overdose of insulin and untimely intake of carbohydrates, hypoglycemic shock can develop - a toxic symptom complex that is accompanied by general weakness, profuse sweating and salivation, dizziness, palpitations, shortness of breath; in severe cases - loss of consciousness, delirium, convulsions, coma.

Contraindications

Acute hepatitis, pancreatitis, nephritis, kidney stones, gastric and duodenal ulcers, decompensated heart disease.

special instructions

Caution in the use of insulin is necessary when prescribing it to patients suffering from coronary insufficiency and cerebrovascular accidents.

When using long-acting drugs, due to the possibility of individual fluctuations in the reaction to the administration of these drugs, it is recommended to examine 3-4 portions of urine for sugar, 24-hour urine for sugar, as well as blood glucose levels. This allows you to clarify the hours of insulin administration, taking into account the time of onset of the maximum glucose-lowering effect.

Long-acting insulin preparations are unsuitable (due to the slow development of the effect) for the treatment of precomatose and comatose states in diabetics.

The effect of insulin is enhanced by simultaneous administration.

Composition and release form

Insulin prescription

Insulin for injection is produced in sterile bottles with a capacity of 5 ml and 10 ml, with an activity of 20 IU, 40 IU or 80 IU in 1 ml of solution.

Insulin for medical use is a white hygroscopic powder, soluble in water, obtained by extraction of the pancreas glands of slaughter cattle (animal insulin) or synthetically. Contains 3.1% sulfur.

Insulin solutions are a clear, colorless or slightly yellowish liquid of an acidic reaction (pH 2.0–3.5), which are prepared by diluting crystalline insulin in water for injection, acidified with hydrochloric acid with the addition of 0.25–0.3% solution or for canning.

Suspensions of prolonged action are produced in sterile bottles of 5 ml and 10 ml, hermetically sealed with rubber stoppers with rolled aluminum caps.

Shelf life and storage conditions

Store with caution (list B) at a temperature of 1–10° C; freezing of insulin preparations is unacceptable.

The shelf life of insulin for injection is 2 years.

Insulin preparations

Suinsulin- an aqueous solution of crystalline insulin obtained from the pancreas of pigs. The drug is used when patients are resistant to the drug obtained from the pancreas of cattle.

Monosulin- a short-acting drug containing crystalline pork insulin, which has a rapid and relatively short-term sugar-lowering effect. It is used for insulin resistance, lipodystrophy, local and general allergic reactions resulting from injections of other insulin preparations. Monosulin is administered subcutaneously or intramuscularly 15–20 minutes before meals one to several times a day. The effect occurs within 15–20 minutes, the maximum effect is achieved after 2 hours, the duration of action of the drug is no more than 6 hours. In case of allergic reactions, an intradermal test (0.02–0.04 IU) is performed before using monosulin. For lipodystrophy, the solution is administered subcutaneously at the border of a healthy and affected area of subcutaneous fat: in children 2–4 units, in adults 4–8 units for 30–40 days. If necessary, the course of treatment is repeated. In case of an overdose, feelings of hunger, weakness, sweating, palpitations, dizziness (hypoglycemia) are possible. Caution is required in case of coronary insufficiency and cerebrovascular accident.

A suspension consisting of suspensions of amorphous and crystalline zinc insulin.

A suspension in the form of an amorphous powder in an acetate buffer with a duration of action of 10–12 hours and maximum effect during the first 7 hours.

A sterile suspension of crystalline insulin in acetate buffer, a drug with a duration of action of up to 36 hours, the maximum occurs 16–20 hours after administration.

A sterile suspension of insulin crystals complexed with protamine in phosphate buffer.

10 ml bottles, composition: insulin - 40 units, zinc chloride - 0.08 mg, tryprotamine - 0.8 ml, glucose - 40 mg, sodium phosphate - about 4 mg, tricresol - 3 mg.

The long-acting drug, in terms of duration of action, occupies a middle place between the regular drug and Triprotamine-zinc-insulin.

Thin suspension of white color. The peculiarity of the suspension, compared to the usual drug, is the slower onset of the effect and its longer duration.

Sterile suspension of crystalline insulin, protamine, zinc chloride and sodium phosphate, long-acting preparation.

Long-acting insulin with the addition of aminoquinurea hydrochloride.

Insulin-long suspension- amorphous pork insulin mixed with zinc and crystalline bovine insulin combined with zinc (in a ratio of 3:7). A long-acting drug, administered subcutaneously and intramuscularly for moderate and severe forms of diabetes mellitus. The hypoglycemic effect occurs after 2–4 hours, reaches maximum activity after 8–10 hours and lasts 20–24 hours. Doses and the number of injections per day are set individually, taking into account the amount of sugar excreted in the urine at different times of the day and the blood sugar level. The drug is not used for diabetic coma and precomatose state. In case of overdose, a hypoglycemic state and allergic reactions (urticaria, rash, skin itching, Quincke's edema) may develop.

Insulin-semilong suspension- contains amorphous pork insulin in combination with zinc. Long-acting drug. Used for moderate and severe diabetes mellitus, for daytime hyperglycemia and glucosuria, administered subcutaneously or intramuscularly. The effect is observed after 1–1.5 hours, maximum activity after 5–8 hours. The duration of action of the drug is 10–12 hours.

Insulin ultralong suspension- contains crystalline bovine insulin in combination with zinc. Used subcutaneously and intramuscularly for moderate and severe diabetes mellitus, in the second half of the night and in the early morning hours. The hypoglycemic effect is observed after 6–8 hours. Duration of action is 30–36 hours.

Properties

(Insulinum) is a high-molecular protein, a hormone produced by the pancreas of mammals, secreted by basophilic insulinocytes (β-cells of the pancreatic islets of Langerhans).

Pharmacological properties

Frederick Banting, Charles Best and James Collip first obtained insulin from the pancreas of animals in 1921.

Insulin is a specific regulator of carbohydrate metabolism, which, by activating hexokinases, promotes the utilization of glucose - its penetration into tissues (mainly into muscles) and combustion, and also stimulates the synthesis of glycogen from glucose in muscle tissue and in the liver, and suppresses gluconeogenesis.

The specific sugar-lowering activity of 0.045 mg of crystalline insulin is taken as a unit of action (U) (1 ml of insulin solution contains 40 IU).

The therapeutic effect and the need for insulin in diabetes mellitus is associated with the elimination of disturbances that occur with this disease in the interstitial metabolism of carbohydrates and fats. This is manifested in an improvement in the general condition of patients, a decrease in blood sugar levels, a reduction or complete elimination of glucosuria and acetonuria, as well as a weakening of a number of body disorders that accompany diabetes mellitus (furunculosis, polyneuritis, polyarthritis, etc.).

Chemical and physical properties

Insulin is easily adsorbed by kaolin, activated carbon and other adsorbents, easily soluble in water, alkalis, acids and weak alcohol solutions; insoluble in 96% alcohol, acetone and ether.

The hormone is inactivated by sunlight (UV radiation), reducing and oxidizing agents, and is easily destroyed by proteolytic enzymes (especially trypsin). The thermal stability of insulin depends on the pH of the medium - in acidic solutions, insulin can withstand boiling for an hour, its stability in alkaline solutions is much lower.

Getting insulin

The most widely accepted method for obtaining animal insulin from the pancreas of pigs and cattle is the following (many modifications of the basic processes vary from manufacturer to manufacturer):

Primary extraction of finely ground pancreatic glands with acidic alcohol.
Evaporation of the alcohol extract under vacuum, degreasing and re-dissolving in 80% alcohol, from which crude insulin is precipitated with absolute alcohol or ether.
Dissolving raw insulin in distilled water and its subsequent purification using one of the following methods: precipitation from an aqueous solution with salts; precipitation of insulin picrate with picric acid; precipitation of insulin at the isoelectric point from a solution with pH=5.0; adsorption on kaolin or activated carbon.

Both insulin salts (usually chloride) and insulin base can be prepared.

Insulin soluble [mixed]

Insulin:: Pharmacological action

Short-acting insulin preparation. Reduces the content of glucose in the blood, enhances its absorption by tissues, increases the intensity of lipogenesis and glycogenogenesis, protein synthesis, and reduces the rate of glucose production by the liver. Interacts with a specific receptor on the outer cell membrane of cells and forms an insulin receptor complex. Through activation of cAMP synthesis (in fat cells and liver cells) or directly penetrating into the cell (muscles), the insulin receptor complex stimulates intracellular processes, incl. synthesis of a number of key enzymes (hexokinase, pyruvate kinase, glycogen synthetase, etc.). The decrease in glucose content in the blood is due to an increase in its intracellular transport, increased absorption and assimilation by tissues, stimulation of lipogenesis, glycogenogenesis, protein synthesis, a decrease in the rate of glucose production by the liver (reduced glycogen breakdown), etc. After subcutaneous injection, the effect occurs within 20-30 min, reaches a maximum after 1-2 hours and lasts, depending on the dose, 5-8 hours. The duration of action of the drug depends on the dose, method, place of administration and has significant individual characteristics.

Insulin:: Indications

Diabetes mellitus type 1, lipodystrophy; diabetes mellitus type 2: stage of resistance to oral hypoglycemic drugs, partial resistance to oral hypoglycemic drugs (combination therapy); diabetic ketoacidosis, ketoacidotic and hyperosmolar coma; diabetes mellitus that occurs during pregnancy (if diet therapy is ineffective); for intermittent use in patients with diabetes mellitus against the background of infections accompanied by high fever; for upcoming surgical operations, injuries, childbirth, metabolic disorders, before switching to treatment with long-acting insulin preparations; insulin resistance due to high titer of anti-insulin antibodies; during transplantation of pancreatic islet cells; for mixing with extended-release human insulins containing protamine as a depot-forming substance. Diagnostic insulin test.

Insulin:: Contraindications

Hypersensitivity, hypoglycemia, insulinoma.

Insulin:: Side effects

Allergic reactions (urticaria, angioedema - fever, shortness of breath, decreased blood pressure); hypoglycemia (pallor of the skin, increased sweating, perspiration, palpitations, tremor, hunger, agitation, anxiety, paresthesia in the mouth, headache, drowsiness, insomnia, fear, depressed mood, irritability, unusual behavior, uncertainty of movements, speech disorders and vision); hyperglycemia and diabetic acidosis (at low doses, missed injections, non-compliance with the diet, against the background of fever and infections): drowsiness, thirst, loss of appetite, facial hyperemia, up to precomatous and comatose states; transient visual disturbances (usually at the beginning of therapy); immunological cross-reactions with human insulin; increased titer of anti-insulin antibodies with subsequent worsening of glycemia; hyperemia, itching and lipodystrophy (atrophy or hypertrophy of subcutaneous fat) at the injection site. Overdose. Symptoms: hypoglycemia (weakness, “cold” sweat, pale skin, palpitations, trembling, nervousness, hunger, paresthesia in the hands, legs, lips, tongue, headache), hypoglycemic coma, convulsions. Treatment: the patient can eliminate mild hypoglycemia on his own by ingesting sugar or foods rich in easily digestible carbohydrates. Glucagon or a hypertonic dextrose solution is administered subcutaneously, intramuscularly or intravenously. When a hypoglycemic coma develops, 20-40 ml (up to 100 ml) of a 40% dextrose solution is injected intravenously until the patient comes out of the comatose state.

Insulin:: Method of administration and dosage

The dose and route of administration of the drug is determined individually in each specific case based on the concentration of glucose in the blood before meals and 1-2 hours after meals, as well as depending on the degree of glucosuria and the characteristics of the course of the disease. The drug is administered subcutaneously, intramuscularly, intravenously, 15-30 minutes before meals. The most common route of administration is subcutaneous. For diabetic ketoacidosis, diabetic coma, during surgery - IV and IM. With monotherapy, the frequency of administration is usually 3 times a day (if necessary, up to 5-6 times a day), the injection site is changed each time to avoid the development of lipodystrophy (atrophy or hypertrophy of subcutaneous fat tissue). The average daily dose is 30-40 IU, in children - 8 IU, then in the average daily dose - 0.5-1 IU/kg or 30-40 IU 1-3 times a day, if necessary - 5-6 times a day. At a daily dose exceeding 0.6 U/kg, insulin must be administered in the form of 2 or more injections into different areas of the body. Can be combined with long-acting insulins. The insulin solution is drawn from the vial by piercing the rubber stopper with a sterile syringe needle, wiped with ethanol after removing the aluminum cap.

Insulin:: Special instructions

If animals are hypersensitive to insulin, insulin tolerance should be tested using skin tests (i.c. injection). If intravenous testing confirms severe insulin hypersensitivity (immediate allergic reaction - Arthus phenomenon), further treatment should only be carried out under clinical supervision. Transferring a patient in case of hypersensitivity to animal insulin to human insulin is often difficult due to the presence of cross-allergy between human and animal insulin. Before taking insulin from the vial, you must check the transparency of the solution. If foreign bodies appear, cloudiness or precipitation of the substance appears on the glass of the bottle, the drug cannot be used. The temperature of the administered insulin should be at room temperature. The insulin dose must be adjusted in cases of infectious diseases, thyroid dysfunction, Addison's disease, hypopituitarism, chronic renal failure and diabetes mellitus in people over 65 years of age. The causes of hypoglycemia can be: insulin overdose, drug replacement, skipping meals, vomiting, diarrhea, physical stress; diseases that reduce the need for insulin (advanced kidney and liver diseases, as well as hypofunction of the adrenal cortex, pituitary gland or thyroid gland), change of injection site (for example, skin on the abdomen, shoulder, thigh), as well as interaction with other drugs. It is possible to reduce the concentration of glucose in the blood when transferring a patient from animal insulin to human insulin. Transferring a patient to human insulin should always be medically justified and carried out only under the supervision of a physician. The tendency to develop hypoglycemia can impair the ability of patients to actively participate in road traffic, as well as to maintain machines and mechanisms. Patients with diabetes can relieve self-perceived mild hypoglycemia by eating sugar or eating foods high in carbohydrates (it is recommended to always have at least 20 g of sugar with you). It is necessary to inform the attending physician about hypoglycemia in order to decide whether treatment adjustments are necessary. When treated with short-acting insulin, in isolated cases there may be a decrease or increase in the volume of adipose tissue (lipodystrophy) in the injection area. These phenomena can be largely avoided by constantly changing the injection site. During pregnancy, it is necessary to take into account a decrease (I trimester) or increase (II-III trimesters) in the need for insulin. During and immediately after childbirth, the need for insulin may decrease dramatically. During lactation, daily monitoring is necessary for several months (until insulin needs stabilize). Patients receiving more than 100 units of insulin per day require hospitalization when changing the drug.

Insulin:: Interaction

Pharmaceutically incompatible with solutions of other drugs. The hypoglycemic effect is enhanced by sulfonamides (including oral hypoglycemic drugs, sulfonamides), MAO inhibitors (including furazolidone, procarbazine, selegiline), carbonic anhydrase inhibitors, ACE inhibitors, NSAIDs (including salicylates), anabolic steroids (including stanozolol, oxandrolone, methandrostenolone), androgens, bromocriptine, tetracyclines, clofibrate, ketoconazole, mebendazole, theophylline, cyclophosphamide, fenfluramine, Li+ preparations, pyridoxine, quinidine, quinine, chloroquinine, ethanol. The hypoglycemic effect weakens glucagon, somatropin, GCS, oral contraceptives, estrogens, thiazide and loop diuretics, BMCK, thyroid hormones, heparin, sulfinpirals, sympathomimetics, Danazole, tricyclic antidepressants, clonidin antagonists, diazopyxides, morphin, morphine marijuana, nicotine, phenytoin, epinephrine, H1-histamine receptor blockers. Beta-blockers, reserpine, octreotide, pentamidine can both enhance and weaken the hypoglycemic effect of insulin.

Today, the pharmaceutical industry produces various forms of insulin. Currently, several types of insulin are used in medicine.

The group affiliation of insulins is most often determined depending on the duration of their action after introduction into the human body. In medicine, there are drugs with the following duration of action:

ultra-short;
short;
average duration of action;
long-acting drugs.

The use of one or another type of insulin depends on the individual characteristics of the patient and the insulin therapy regimen for diabetes mellitus.

Different types of insulin differ from each other both in composition and in the method of synthesis. For each type of insulin preparation, instructions for use are developed in accordance with the characteristics of the composition and method of obtaining the drug.

In addition, there are general requirements that should be met when carrying out insulin therapy. Each insulin drug has certain indications and contraindications for use.

What is insulin?

Insulin is a protein-peptide drug of hormonal origin. Insulin is used as a specific agent in the treatment of diabetes mellitus.

Insulin is a hormone that takes an active part in carbohydrate metabolism and helps reduce the concentration of glucose in the patient's blood plasma. Reducing carbohydrates in the blood is achieved by activating the consumption of sugars by insulin-dependent tissues under the influence of insulin. Insulin promotes the process of glycogen synthesis by liver cells and prevents the conversion of fats and amino acids into carbohydrates.

With a lack of insulin in the human body, an increase in the level of sugar levels in the blood plasma is observed. An increase in blood glucose provokes the development of diabetes mellitus and related complications. A lack of insulin in the body occurs as a result of disturbances in the functioning of the pancreas, which appear due to malfunctions of the endocrine system, after injury, or due to severe psychological stress on the body associated with the occurrence of stressful situations.

Preparations containing insulin are made from animal pancreatic tissue.

Most often, pancreatic tissue from cattle and pigs is used in the production of drugs.

Indications for the use of insulin drugs

Sugar level

To eliminate an overdose of drugs containing insulin, you need to take 100 grams of white bread, sweet tea or a few spoons of sugar at the first symptoms of dosage.

If there are severe signs of shock, glucose should be administered to the patient intravenously. If necessary, you can additionally administer adrenaline subcutaneously.

Particular caution is required when using insulin of synthetic origin in patients with diabetes mellitus, if they have coronary insufficiency and if disorders in the cerebral circulation are detected. When using long-acting insulin, a systematic examination of the patient’s urine and blood for sugar content is required. Such a study will clarify the optimal time of taking the drug to achieve the maximum positive effect.

To administer the drug, special insulin syringes or special syringe pens are most often used.

The use of syringes or pens depends on the type of insulin used during insulin therapy.

Diabetes mellitus is a serious disease that is chronic. The human pancreas is an organ of the endocrine system that produces the vital hormone insulin. Insulin carries out the metabolism of glucose, which is necessary for the brain and the entire body to function. With diabetes, the pancreas is unable to function normally. Therefore, the patient needs to take medications regularly. In most cases, tablets are sufficient. But insulin-dependent diabetes requires regular insulin injections.

Carrying out treatment

Mild forms of diabetes can be treated with diet alone. But more often the patient requires medication. The most severe form of diabetes mellitus, the insulin-dependent type of the disease, occurs in approximately 10-15% of cases. But one type is capable of transforming into another.

Patients with insulin-dependent diabetes require lifelong administration of artificial insulin in most cases. Most often this is synthesized bovine or porcine insulin, which contain various impurities. This distinguishes the insulin administered to the patient from the hormone produced by the human pancreas.

Side effects

When using insulin injections to maintain the normal state of a diabetic, as with any treatment, insulin side effects may occur. Some of them do not cause serious concern, but some manifestations are very serious.

This does not mean that the patient should refuse insulin injections. This is dangerous for his life. It is important to simply choose the right drug so that it suits a particular patient. Most often, switching to purified insulin eliminates most of the unwanted effects. If this does not help, then the patient should undergo an additional course of treatment. In any case, it is impossible for a diabetic with an insulin-dependent type of disease to refuse injections.

Possible body reactions

Insulin injections can cause various side effects.

Hypoglycemia is the most common side effect of therapy. This is a pathological condition characterized by low blood glucose levels below normal. This occurs when the drug is overdosed. A person’s heart rate increases, anxiety and fear arise, and the skin becomes pale. Dizziness, fainting, increased sweating and body trembling are possible. An increased feeling of hunger occurs, which should be satisfied to alleviate the patient’s condition (it is better to consume fast carbohydrates). In the most severe cases, epileptiform seizures, coma and death are possible.

Another common side effect is insulin allergy. It is most often associated with a reaction to drug impurities. It is often accompanied by tissue atrophy at the injection site.

Somogyi syndrome is post-hypoglycemic hyperglycemia. Changes in blood glucose levels cause undesirable consequences for a diabetic.

Lipodystrophy is a pathology of the subcutaneous tissue in the injection area, which manifests itself in its disappearance or excessive growth. It is recommended to change injection sites more often.

Insulin edema - most often occurs at the beginning of treatment, but goes away over time. Does not require therapy.