Pancreatic hormonal drugs. Biological role of pancreatic hormones

Antithyroid drugs are used for hyperfunction of the thyroid gland (thyrotoxicosis, Graves' disease). Currently, the most commonly used antithyroid drugs are thiamazole (mercazolyl), which inhibits thyroperoxidase and thus prevents the iodination of tyrosine residues of thyroglobulin and disrupts the synthesis of T 3 and T 4. Prescribed internally. When using this drug, leukopenia, agranulocytosis, and skin rashes are possible. Possible enlargement of the thyroid gland.

Iodides are prescribed orally as antithyroid drugs - kalia iodide or sodium iodide in fairly high doses (160-180 mg). In this case, iodides reduce the production of thyroid-stimulating hormone by the pituitary gland; accordingly, the synthesis and release of T 3 and T 4 decreases. A similar mechanism of inhibition of thyroid-stimulating hormone release is also observed when using diiodotyrosine. The drugs are used orally. Causes a decrease in the volume of the thyroid gland. Side effects: headache, lacrimation, conjunctivitis, pain in the salivary glands, laryngitis, skin rashes.

3.Preparation of hormone of parafollicular cells of the thyroid gland

Parafollicular cells of the thyroid gland secrete calcitonin, which prevents bone decalcification by reducing the activity of osteoclasts. The consequence of this is a decrease in the content of calcium ions in the blood. A drug calcitonin used for osteoporosis.

Parathyroid hormone drug

The polypeptide hormone of the parathyroid glands, parathyroid hormone, affects the metabolism of calcium and phosphorus. Causes decalcification of bone tissue. Promotes the absorption of calcium ions from the gastrointestinal tract, increases the reabsorption of calcium and reduces the reabsorption of phosphate in the renal tubules. In this regard, when acting parathyroid hormone increases the level of Ca 2+ in the blood plasma. Medicinal preparation from the parathyroid glands of slaughter cattle parathyroidin used for hypoparathyroidism, spasmophilia.

Pancreatic hormone preparations

The pancreas is an external and internal secretion gland. β-cells of the islets of Langerhans produce insulin, α-cells produce glucagon. These hormones have the opposite effect on blood glucose levels: insulin lowers it, and glucagon increases it.

1. Insulin preparations and synthetic hypoglycemic agents

Insulin stimulates cell membrane receptors coupled to tyrosine kinase. In this regard, insulin:

promotes the uptake of glucose by tissue cells (with the exception of the central nervous system), facilitating the transport of glucose through cell membranes;

reduces gluconeogenesis in the liver;

3) stimulates the formation of glycogen and its deposition in the liver;

4) promotes the synthesis of proteins and fats and prevents their catabolism;

5) reduces glycogenolysis in the liver and skeletal muscles.

With insufficient insulin production, diabetes mellitus develops, in which carbohydrate, fat and protein metabolism is disrupted.

Type I diabetes mellitus (insulin-dependent) is associated with the destruction of β-cells of the islets of Langerhans. The main symptoms of type I diabetes mellitus: hyperglycemia, glycosuria, polyuria, thirst, polydipsia (increased fluid intake), ketonemia, ketonuria, ketacidosis. Severe forms of diabetes without treatment are fatal; death occurs in a state of hyperglycemic coma (significant hyperglycemia, acidosis, unconsciousness, the smell of acetone from the mouth, the appearance of acetone in the urine, etc.). For type I diabetes mellitus, the only effective treatments are insulin preparations administered parenterally.

Type II diabetes mellitus (non-insulin-dependent) is associated with a decrease in insulin secretion (decreased β-cell activity) or with the development of tissue resistance to insulin. Insulin resistance may be due to a decrease in the number or sensitivity of insulin receptors. In this case, insulin levels may be normal or even elevated. Elevated insulin levels promote obesity (an anabolic hormone), which is why type II diabetes is sometimes called obese diabetes. For type II diabetes mellitus, oral hypoglycemic agents are used, which, if their effectiveness is insufficient, are combined with insulin preparations.

Insulin preparations

Currently, the best insulin preparations are recombinant human insulin preparations. In addition to them, insulin preparations obtained from the pancreas of pigs (pork insulin) are used.

Human insulin preparations are obtained using genetic engineering methods.

Human insulin soluble(Actrapid NM) is produced in bottles of 5 and 10 ml containing 40 or 80 units per 1 ml, as well as in cartridges of 1.5 and 3 ml for syringe pens. The drug is usually administered under the skin 15-20 minutes before meals 1-3 times a day. The dose is selected individually depending on the severity of hyperglycemia or glycosuria. The effect develops after 30 minutes and lasts 6-8 hours. Lipodystrophy may develop at the sites of subcutaneous insulin injections, so it is recommended to constantly change the injection site. In diabetic coma, insulin can be administered intravenously. In case of insulin overdose, hypoglycemia develops. Pallor, sweating, a strong feeling of hunger, trembling, palpitations, irritability, and tremors appear. Hypoglycemic shock (loss of consciousness, convulsions, cardiac dysfunction) may develop. At the first signs of hypoglycemia, the patient should eat sugar, cookies, or other foods rich in glucose. In case of hypoglycemic shock, glucagon is administered intramuscularly or a 40% glucose solution is administered intravenously.

Zinc crystalline suspension of human insulin(ultratard NM) is administered only under the skin. Insulin is slowly absorbed from the subcutaneous tissue; the effect develops after 4 hours; maximum effect after 8-12 hours; duration of action is 24 hours. The drug can be used as a base agent in combination with fast and short-acting drugs.

Porcine insulin preparations are similar in action to human insulin preparations. However, when using them, allergic reactions are possible.

Insulinsolubleneutral Available in 10 ml bottles containing 40 or 80 units per ml. Injected under the skin 15 minutes before meals 1-3 times a day. Intramuscular and intravenous administration is possible.

Insulin- zincsuspensionamorphous is injected only under the skin, ensuring slow absorption of insulin from the injection site and, accordingly, a longer action. Onset of action after 1.5 hours; peak action after 5-10 hours; duration of action – 12-16 hours.

Insulin-zinc suspension crystalline injected only under the skin. Onset of action after 3-4 hours; peak action after 10-30 hours; duration of action is 28-36 hours.

Synthetic hypoglycemic agents

The following groups of synthetic hypoglycemic agents are distinguished:

1) sulfonylurea derivatives;

2) biguanides;

Sulfonylurea derivatives – butamide, chlorpropamide, glibenclamide prescribed internally. These drugs stimulate insulin secretion by the β-cells of the islets of Langerhans.

The mechanism of action of sulfonylurea derivatives is associated with blockade of ATP-dependent K + channels of β-cells and depolarization of the cell membrane. In this case, voltage-dependent Ca 2+ channels are activated; Ca g+ entry stimulates insulin secretion. In addition, these substances increase the sensitivity of insulin receptors to the action of insulin. It has also been shown that sulfonylurea derivatives increase the stimulating effect of insulin on the transport of glucose into cells (fat, muscle). Sulfonylurea derivatives are used for type II diabetes mellitus. Ineffective for type I diabetes mellitus. Absorbed into the gastrointestinal tract quickly and completely. Most of it binds to blood plasma proteins. Metabolized in the liver. Metabolites are excreted mainly by the kidneys, and can be partially excreted in bile.

Side effects: nausea, metallic taste in the mouth, pain in the stomach, leukopenia, allergic reactions. In case of overdose of sulfonylurea derivatives, hypoglycemia is possible. The drugs are contraindicated in cases of dysfunction of the liver, kidneys, or blood system.

Biguanides – metformin prescribed internally. Metformin:

1) increases the uptake of glucose by peripheral tissues, especially muscles,

2) reduces gluconeogenesis in the liver,

3) reduces the absorption of glucose in the intestine.

In addition, metformin reduces appetite, stimulates lipolysis and inhibits lipogenesis, resulting in a decrease in body weight. Prescribed for type II diabetes mellitus. The drug is well absorbed, the duration of action is up to 14 hours. Side effects: lactic acidosis (increased levels of lactic acid in the blood plasma), pain in the heart and muscles, shortness of breath, as well as a metallic taste in the mouth, nausea, vomiting, diarrhea.

Pancreatic hormone preparations

The human pancreas, mainly in its caudal part, contains approximately 2 million islets of Langerhans, constituting 1% of its mass. The islets consist of a-, b- and l-cells that produce glucagon, insulin and somatostatin (inhibiting the secretion of growth hormone), respectively.

In this lecture, we are interested in the secret of b-cells of the islets of Langerhans - INSULIN, since insulin preparations are currently the leading antidiabetic agents.

Insulin was first isolated in 1921 by Banting, Best - for which they received the Nobel Prize in 1923. Insulin was isolated in crystalline form in 1930 (Abel).

Normally, insulin is the main regulator of blood glucose levels. Even a slight increase in blood glucose causes insulin secretion and stimulates its further synthesis by b-cells.

The mechanism of action of insulin is due to the fact that hubbub enhances the absorption of glucose by tissues and promotes its conversion into glycogen. Insulin, by increasing the permeability of cell membranes to glucose and reducing the tissue threshold to it, facilitates the penetration of glucose into cells. In addition to stimulating the transport of glucose into the cell, insulin stimulates the transport of amino acids and potassium into the cell.

Cells are very permeable to glucose; In them, insulin increases the concentration of glucokinase and glycogen synthetase, which leads to the accumulation and deposition of glucose in the liver in the form of glycogen. In addition to hepatocytes, striated muscle cells are also glycogen depots.

With a lack of insulin, glucose will not be properly absorbed by the tissues, which will result in hyperglycemia, and with very high levels of glucose in the blood (more than 180 mg/l) and glycosuria (sugar in the urine). Hence the Latin name for diabetes: “Diabetes mellitus” (diabetes).

The tissue requirement for glucose varies. In a number of fabrics

The brain, visual epithelial cells, sperm-producing epithelium - energy production occurs only due to glucose. Other tissues may use fatty acids in addition to glucose to produce energy.

In diabetes mellitus (DM), a situation arises in which, amid “abundance” (hyperglycemia), cells experience “hunger.”

In the patient’s body, in addition to carbohydrate metabolism, other types of metabolism are also distorted. In insulin deficiency, there is a negative nitrogen balance when amino acids are primarily used in gluconeogenesis, that wasteful conversion of amino acids into glucose, when 100 g of protein produces 56 g of glucose.

Fat metabolism is also impaired, and this is primarily due to an increase in the blood level of free fatty acids (FFA), from which ketone bodies (acetoacetic acid) are formed. The accumulation of the latter leads to ketoacidosis up to coma (coma is an extreme degree of metabolic disorder in diabetes). In addition, under these conditions, cell resistance to insulin develops.

According to WHO, currently the number of people with diabetes on the planet has reached 1 billion people. In terms of mortality, diabetes ranks third after cardiovascular pathology and malignant neoplasms, so diabetes is an acute medical and social problem that requires emergency measures to solve.

According to the current WHO classification, the population of patients with diabetes is divided into two main types

1. Insulin-dependent diabetes mellitus (formerly called juvenile diabetes mellitus) - IDDM (DM-I) develops as a result of the progressive death of b-cells, and is therefore associated with insufficient insulin secretion. This type debuts before the age of 30 years and is associated with a multifactorial mode of inheritance, as it is associated with the presence of a number of histocompatibility genes of the first and second classes, for example, HLA-DR4 and HLA-DR3. Individuals with both -DR4 and -DR3 antigens are at greatest risk of developing IDDM. The proportion of patients with IDDM is 15-20% of the total.

2. Non-insulin-dependent diabetes mellitus - NIDDM (DM-II). This form of diabetes is called adult-onset diabetes because it usually appears after age 40.

The development of this type of diabetes is not associated with the human major histocompatibility system. In patients with this type of diabetes, a normal or moderately reduced number of insulin-producing cells is found in the pancreas, and it is currently believed that NIDDM develops as a result of a combination of insulin resistance and a functional impairment of the patient's b-cells' ability to secrete compensatory amounts of insulin. The proportion of patients with this form of diabetes is 80-85%.

In addition to two main types, there are:

3. Diabetes associated with malnutrition.

4. Secondary, symptomatic diabetes (endocrine origin: goiter, acromegaly, pancreatic diseases).

5. Diabetes in pregnant women.

Currently, a certain methodology has emerged, that is, a system of principles and views on the treatment of patients with diabetes, the key of which are:

1) compensation for insulin deficiency;

2) correction of hormonal and metabolic disorders;

3) correction and prevention of early and late complications.

According to the latest treatment principles, the following three traditional components remain the main methods of treatment for patients with diabetes:

2) insulin preparations for patients with IDDM;

3) oral hypoglycemic agents for patients with NIDDM.

In addition, compliance with the regime and degree of physical activity is important. Among the pharmacological agents used to treat patients with diabetes, there are two main groups of drugs:

I. Insulin preparations.

II. Synthetic oral (tablet) antidiabetic agents.

Parathyroidin- the drug parathyroid hormone parathyrin (parathyroid hormone), has recently been used very rarely, as there are more effective means. Regulation of the production of this hormone depends on the amount of Ca 2+ in the blood. The pituitary gland does not affect the synthesis of parathyrin.

Pharmacological is the regulation of calcium and phosphorus metabolism. Its target organs are bones and kidneys, which have specific membrane receptors for parathyrin. In the intestine, parathyrin activates the absorption of calcium and inorganic phosphate. It is believed that the stimulating effect on calcium absorption in the intestine is associated not with the direct influence of parathyrin, but with an increase in formation under its influence calcitriol (the active form of calciferol in the kidneys). In the renal tubules, parathyrine increases calcium reabsorption and decreases phosphate reabsorption. At the same time, the phosphorus content in the blood decreases, while the calcium level increases.

Normal levels of parathyrin have an anabolic (osteoplastic) effect with increased bone growth and mineralization. With hyperfunction of the parathyroid glands, osteoporosis occurs, hyperplasia of fibrous tissue, which leads to bone deformation and fractures. In cases of hyperproduction of parathyrin, administer calcitonin, which prevents the leaching of calcium from bone tissue.

Indications: hypoparathyroidism, to prevent tetany due to hypocalcemia (in acute cases, calcium supplements or their combination with parathyroid hormone preparations should be administered intravenously).

Contraindications: increased calcium content in the blood, with heart disease, kidney disease, allergic diathesis.

Dihydrotachysterol (tahistin) - its chemical structure is close to ergocalciferol (vitamin D2). Increases the absorption of calcium in the intestines, while simultaneously increasing the excretion of phosphorus in the urine. Unlike ergocalciferol, there is no vitamin D activity.

Indications: disorders of phosphorus-calcium metabolism, including hypocalcic convulsions, spasmophilia, allergic reactions, hypoparathyroidism.

Contraindications: increased calcium levels in the blood.

Side effect: nausea.

Pancreatic hormonal drugs.

insulin preparations

Pancreatic hormones are of great importance in regulating metabolic processes in the body. IN β cells pancreatic islets are synthesized insulin, which has a pronounced hypoglycemic effect, in a-cells contrainsular hormone is produced glucagon, which has a hyperglycemic effect. Besides, δ-clititis pancreas produces somatostatin .

When insulin secretion is insufficient, diabetes mellitus (DM) develops - diabetes mellitus - a disease that occupies one of the dramatic pages of world medicine. According to WHO estimates, the number of people with diabetes worldwide in 2000 was 151 million people; by 2010, it is expected to increase to 221 million people, and by 2025 - 330 million people, which suggests that it is a global epidemic. Diabetes causes the earliest disability of all diseases, high mortality, frequent blindness, renal failure, and is also a risk factor for cardiovascular diseases. Diabetes ranks first among endocrine diseases. The United Nations has declared diabetes to be a pandemic of the 21st century.

According to the WHO classification (1999.) There are two main types of the disease - diabetes type 1 and type 2(according to insulin-dependent and non-insulin-dependent diabetes). Moreover, the increase in the number of patients is predicted mainly due to patients with type 2 diabetes, who currently make up 85-90% of the total number of patients with diabetes. This type of diabetes is diagnosed 10 times more often than type 1 diabetes.

For the treatment of diabetes, diet, insulin preparations and oral antidiabetic drugs are used. Effective treatment of patients with CD should ensure approximately the same basal insulin levels throughout the day and prevent hyperglycemia that occurs after eating (postprandial glycemia).

The main and only objective indicator of the effectiveness of diabetes therapy, reflecting the state of disease compensation, is the level of glycosylated hemoglobin (HbA1C or A1C). HbA1c or A1C is hemoglobin, which is covalently bound to glucose and is an indicator of the level of glycemia over the previous 2-3 months. Its level correlates well with blood glucose levels and the likelihood of diabetes complications. A 1% decrease in the level of glycosylated hemoglobin is accompanied by a 35% decrease in the risk of developing diabetes complications (regardless of the initial HbA1c level).

The basis of treatment for CD is properly selected hypoglycemic therapy.

Historical reference. The principles of producing insulin were developed by L.V. Sobolev (in 1901), who in an experiment on the glands of newborn calves (they do not yet contain trypsin, insulin breaks down) showed that the substrate of the internal secretion of the pancreas is the pancreatic islets (Langerhans). In 1921, Canadian scientists F. G. Banting and C. H. Best isolated pure insulin and developed a method for industrial production. 33 years later, Sanger and his colleagues deciphered the primary structure of cattle insulin, for which they received the Nobel Prize.

The creation of insulin preparations occurred in several stages:

First generation insulins - pork and cow (bovine) insulin;

Second generation insulins - monopeak and monocomponent insulins (50s of the XX century)

Third generation insulins - semi-synthetic and genetically engineered insulin (80s of the 20th century)

Preparation of insulin analogues and inhaled insulin (late 20th - early 21st centuries).

Animal insulins differed from human insulin in amino acid composition: bovine insulin - in amino acids in three positions, pork - in one position (position 30 in chain B). When treated with bovine insulin, adverse immunological reactions occurred more often than when treated with porcine or human insulin. These reactions were expressed in the development of immunological resistance and allergy to insulin.

To reduce the immunological properties of insulin preparations, special purification methods have been developed, which made it possible to obtain a second generation. First there were monopeak and insulins obtained by gel chromatography. It was later found that they contain small amounts of insulin-like peptides. The next step was the creation of monocomponent insulins (MK-insulins), which were obtained through additional purification using ion exchange chromatography. When using monocomponent porcine insulins, the production of antibodies and the development of local reactions in patients were rare (currently bovine and monopik and porcine insulins are not used in Ukraine).

Human insulin preparations are obtained either by a semi-synthetic method using an enzymatic-chemical replacement at position B30 in pork insulin of the amino acid alanine with threonine, or by a biosynthetic method using genetic engineering technology. Practice has shown that there is no significant clinical difference between human insulin and high-quality monocomponent porcine insulin.

Now work continues to improve and search for new forms of insulin.

According to its chemical structure, insulin is a protein, the molecule of which consists of 51 amino acids, forming two polypeptide chains connected by two disulfide bridges. Concentration plays a dominant role in the physiological regulation of insulin synthesis. glucose in blood. Penetrating into β-cells, glucose is metabolized and contributes to an increase in the intracellular ATP content. The latter, by blocking ATP-dependent potassium channels, causes depolarization of the cell membrane. This promotes the entry of calcium ions into β-cells (through voltage-gated calcium channels that have opened) and the release of insulin by exocytosis. In addition, insulin secretion is influenced by amino acids, free fatty acids, glucagon, secretin, electrolytes (especially Ca 2+), and the autonomic nervous system (the sympathetic nervous system is inhibitory, and the parasympathetic nervous system is stimulating).

Pharmacodynamics. The action of insulin is aimed at the metabolism of carbohydrates, proteins, fats, and minerals. The main thing in the action of insulin is its regulating effect on carbohydrate metabolism and reducing blood glucose levels. This is achieved by the fact that insulin promotes the active transport of glucose and other hexoses, as well as pentoses across cell membranes and their utilization by the liver, muscle and fat tissues. Insulin stimulates glycolysis, induces the synthesis of the enzymes glucokinase, phosphofructokinase and pyruvate kinase, stimulates the pentose phosphate cycle, activating glucose-6-phosphate dehydrogenase, increases glycogen synthesis, activating glycogen synthetase, the activity of which is reduced in patients with diabetes. On the other hand, the hormone suppresses glycogenolysis (decomposition of glycogen) and gluconeogenesis.

Insulin plays an important role in stimulating the biosynthesis of nucleotides, increasing the content of 3.5 nucleotases, nucleoside triphosphatase, including in the nuclear envelope, where it regulates the transport of mRNA from the nucleus to the cytoplasm. Insulin stimulates the biosynthesis of nucleic acids and proteins. In parallel to the enhancement of anabolic processes, insulin inhibits the catabolic reactions of the breakdown of protein molecules. It also stimulates the processes of lipogenesis, the formation of glycerol, and its introduction into lipids. Along with the synthesis of triglycerides, insulin activates the synthesis of phospholipids (phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and cardiolipin) in fat cells and also stimulates the biosynthesis of cholesterol, which, like phospholipids and some glycoproteins, is necessary for the construction of cell membranes.

With insufficient amounts of insulin, lipogenesis is suppressed, lipid production increases, lipid peroxidation in the blood and urine increases the level of ketone bodies. Due to the reduced activity of lipoprotein lipase in the blood, the concentration of β-lipoproteins, which are essential in the development of atherosclerosis, increases. Insulin prevents the body from losing fluid and K+ in the urine.

The essence of the molecular mechanism of insulin action on intracellular processes is not fully disclosed. However, the first link in the action of insulin is binding to specific receptors on the plasma membrane of target cells, primarily in the liver, adipose tissue and muscles.

Insulin binds to the α subunit of the receptor (contains the main insulin-binding domain). In this case, the kinase activity of the β-subunit of the receptor (Tyrosine kinase) is stimulated and it autophosphorylates. An “insulin + receptor” complex is created, which penetrates into the cell through endocytosis, where insulin is released and the cellular mechanisms of the hormone’s action are triggered.

Not only secondary messengers take part in the cellular mechanisms of insulin action: cAMP, Ca 2+, calcium-calmodulin complex, inositol triphosphate, diacylglycerol, but also fructose 2,6-biphosphate, which is called the third mediator of insulin in its effect on intracellular biochemical processes. It is the increase in the level of fructose-2,6-biphosphate under the influence of insulin that promotes the utilization of glucose from the blood and the formation of fats from it.

The number of receptors and their ability to bind is influenced by a number of factors. In particular, the number of receptors is reduced in cases of obesity, non-insulin-dependent type 2 diabetes, and peripheral hyperinsulinism.

Insulin receptors exist not only on the plasma membrane, but also in the membrane components of such internal organelles as the nucleus, endoplasmic reticulum, and Golgi complex. Administration of insulin to patients with diabetes helps reduce blood glucose levels and the accumulation of glycogen in tissues, reducing glucosuria and associated polyuria and polydipsia.

Due to the normalization of protein metabolism, the concentration of nitrogen compounds in the urine decreases, and as a result of the normalization of fat metabolism, ketone bodies - acetone, acetoacetic and hydroxybutyric acids - disappear from the blood and urine. Losing weight stops and excessive hunger disappears ( bulimia ). The detoxification function of the liver increases, and the body's resistance to infections increases.

Classification. Modern insulin preparations differ from each other speed And duration of action. They can be divided into the following groups:

1. Short-acting insulin preparations, or simple insulins ( Actrapid MK , humulin etc.) The decrease in blood glucose levels after their subcutaneous administration begins after 15-30 minutes, the maximum effect is observed after 1.5-3 hours, the effect lasts 6-8 hours.

Significant advances in the study of molecular structure, biological activity and medicinal properties have led to modifications in the formula of human insulin and to the development of short-acting insulin analogues.

The first analogue is lisproinsulin (humalogist) is identical to human insulin except for the position of lysine and proline at positions 28 and 29 of the B chain. This change did not affect the activity of the A-chain, but reduced the processes of self-association of insulin molecules and ensured accelerated absorption from the subcutaneous depot. After injection, the onset of action is 5-15 minutes, the peak is reached in 30-90 minutes, the duration of action is 3-4 hours.

The second analogue is aspart(tradename - novo-rapid) modified by replacing one amino acid at position B-28 (proline) with aspartic acid, reduces the phenomenon of cell self-aggregation of insulin molecules into dimmers and hexamers and accelerates its absorption.

The third analogue is glulisine(tradename epaidra) is practically similar to endogenous human insulin and biosynthetic regular human insulin with certain structural changes in the formula. Thus, in the V3-position, asparagine is replaced by lysine, and lysine in position B29 is replaced by glutamic acid. By stimulating the peripheral use of glucose by skeletal muscles and adipose tissue, inhibiting gluconeogenesis in the liver, glulisine (epaidra) improves glycemic control, also inhibits lipolysis and proteolysis, accelerates protein synthesis, activates insulin receptors and its substrates, fully consistent with the effect of regular human insulin on these elements.

2. Long-acting insulin preparations:

2.1. Medium duration (onset of action after subcutaneous administration after 1.5-2 hours, duration 8-12 hours). These drugs are also called insulin semilente. This group includes insulins based on neutral Protamine Hagedorn: B-insulin, Monodar B, Farmasulin HNP. Since HNP-insulin contains insulin and protamine in equal, isophane-based ratios, they are also called isophane-type insulins;

2.2. Long-lasting (ultralente) with onset of action after 6-8 hours, duration of action 20-30 hours. This includes insulin preparations containing Zn2 +: suspension-insulin-ultralente, Farmasulin HL. Long-acting drugs are administered only subcutaneously or intramuscularly.

3. Combined preparations containing standard mixtures of drugs of group 1 with NPH insulins in different ratios of groups 1 and 2: 30/70, 20/80, 10/90, etc. - Monodar K ZO, Farmasulin 30/70 t. Some drugs are produced in special syringe tubes.

To achieve maximum glycemic control in patients with diabetes, an insulin therapy regimen is needed that completely simulates the physiological profile of insulin throughout the day. Long-acting insulins have their drawbacks, in particular the presence of a peak effect 5-7 hours after administration of the drug leads to the development of hypoglycemia, especially at night. These shortcomings have led to the development of insulin analogues with the pharmacokinetic properties of effective basal insulin therapy.

One of these drugs created by Aventis is insulin glargine (Lantus), which differs from human by three amino acid residues. Glargine-in Sulin is a stable insulin structure, completely soluble at pH 4.0. The drug does not dissolve in subcutaneous tissue, which has a pH of 7.4, which leads to the formation of microprecipitates at the injection site and its slow release into the bloodstream. The addition of a small amount of zinc (30 mcg/ml) helps slow down absorption. Being slowly absorbed, insulin glargine does not have a peak effect and provides almost basal insulin concentrations throughout the day.

New promising insulin preparations are being developed - inhaled insulin (creation of an insulin-air mixture for inhalation) oral insulin (oral spray); buccal insulin (in the form of oral drops).

A new method of insulin therapy is the administration of insulin using an insulin pump, which provides a more physiological method of administering the drug, the absence of an insulin depot in the subcutaneous tissue.

The activity of insulin preparations is determined by the method of biological standardization and is expressed in units. 1 unit corresponds to the activity of 0.04082 mg of crystalline insulin. The dose of insulin for each patient is selected individually in a hospital setting with constant monitoring of HbA1c levels in the blood and sugar levels in the blood and urine after the drug is prescribed. When calculating the daily dose of insulin, it should be taken into account that 1 unit of insulin promotes the absorption of 4-5 g of sugar excreted in the urine. The patient is put on a diet with a limited amount of easily digestible carbohydrates.

Simple insulins are administered 30-45 minutes before meals. Intermediate-acting insulins are usually used twice (half an hour before breakfast and at 18.00 before dinner). Long-acting drugs are administered together with simple insulins in the morning.

There are two main types of insulin therapy: traditional and intensive.

Traditional insulin therapy- this is the administration of standard mixtures of short-acting insulin and NPH-insulin 2/3 doses before breakfast, 1/3 before dinner. However, with this type of therapy, hyperinsulinemia occurs, which requires 5-6 times the consumption of food during the day, the development of hypoglycemia is possible, and a high incidence of late complications of diabetes.

Intensive (basal-bolus) insulin therapy- this is the use of intermediate-acting insulin twice a day (to create a basal level of the hormone) and the additional administration of short-acting insulin before breakfast, lunch and dinner (simulating bolus physiological secretion of insulin in response to food intake). With this type of therapy, the patient himself selects the dose of insulin based on measuring the glycemic level using a glucometer.

Indications: Insulin therapy is absolutely indicated for patients with type 1 diabetes. It should be started in those patients in whom diet, normalization of body weight, physical activity and oral antidiabetic drugs do not provide the necessary effect. Simple insulin is used for diabetic coma, as well as for diabetes of any type, if it is accompanied by complications: ketoacidosis, infection, gangrene, heart disease, liver disease, surgical operations, postoperative period; to improve the nutrition of patients exhausted by a long-term illness; as part of a polarizing mixture for heart diseases.

Contraindications: diseases with hypoglycemia, hepatitis, liver cirrhosis, pancreatitis, glomerulonephritis, kidney stones, gastric and duodenal ulcers, decompensated heart defects; for long-acting drugs - coma, infectious diseases, during surgical treatment of patients with diabetes.

Side effect painful injections, local inflammatory reactions (infiltrates), allergic reactions, the emergence of drug resistance, the development of lipodystrophy.

An overdose of insulin may cause hypoglycemia. Symptoms of hypoglycemia: anxiety, general weakness, cold sweat, trembling limbs. A significant decrease in blood sugar leads to impaired brain function, coma, seizures and even death. Patients with diabetes should have several pieces of sugar with them to prevent hypoglycemia. If, after taking sugar, the symptoms of hypoglycemia do not disappear, you need to urgently inject 20-40 ml of a 40% glucose solution intravenously; 0.5 ml of a 0.1% adrenaline solution can be injected subcutaneously. In cases of significant hypoglycemia due to the action of long-acting insulin preparations, it is more difficult to recover patients from this condition than from hypoglycemia caused by short-acting insulin preparations. The presence of protamine protein in some long-acting drugs explains the frequent cases of allergic reactions. However, injections of long-acting insulin preparations are less painful, which is associated with the higher pH of these drugs.

The pancreas is the most important digestive gland, producing a large number of enzymes that digest proteins, lipids, and carbohydrates. It is also an gland that synthesizes insulin and one of the hormones that suppresses the action - glucagon. When the pancreas cannot cope with its functions, it is necessary to take pancreatic hormone preparations. What are the indications and contraindications for taking these medications?

The pancreas is an important digestive organ.

- This is an elongated organ located closer to the back of the abdominal cavity and slightly extending to the area of the left side of the hypochondrium. The organ includes three parts: head, body, tail.

Large in volume and extremely necessary for the functioning of the body, the gland produces external and intrasecretory work.

Its exocrine region has classic secretory sections, the ductal part, where the formation of pancreatic juice necessary for the digestion of food, the decomposition of proteins, lipids, and carbohydrates occurs.

The endocrine region includes the pancreatic islets, which are responsible for the synthesis of hormones and control of carbohydrate-lipid metabolism in the body.

An adult normally has a head of the pancreas measuring 5 cm or more, the thickness of this area is within 1.5-3 cm. The width of the body of the gland is approximately 1.7-2.5 cm. The tail part can be up to 3.5 cm in length. 5 cm, and up to one and a half centimeters in width.

The entire pancreas is covered with a thin capsule of connective tissue.

The mass of the pancreatic gland of an adult is in the range of 70-80 g.

Pancreatic hormones and their functions

The organ performs external and intrasecretory work

The two main hormones of the organ are insulin and glucagon. They are responsible for lowering and raising sugar levels.

Insulin production is carried out by β-cells of the islets of Langerhans, which are concentrated mainly in the tail of the gland. Insulin is responsible for bringing glucose into cells, stimulating its absorption and lowering blood sugar levels.

The hormone glucagon, on the contrary, increases the amount of glucose, stopping hypoglycemia. The hormone is synthesized by α-cells that make up the islets of Langerhans.

Interesting fact: alpha cells are also responsible for the synthesis of lipocaine, a substance that prevents the formation of fatty deposits in the liver.

In addition to alpha and beta cells, the islets of Langerhans are approximately 1% formed from delta cells and 6% from PP cells. Delta cells produce ghrelin, an appetite hormone. PP cells synthesize pancreatic polypeptide, which stabilizes the secretory function of the gland.

The pancreas produces hormones. All of them are necessary to maintain human life. Read more about gland hormones below.

Insulin

Insulin in the human body is produced by special cells (beta cells) of the pancreatic gland. These cells are located in a large volume in the tail part of the organ and are called the islets of Langerhans.

Insulin controls blood glucose levels

Insulin is primarily responsible for controlling blood glucose levels. The process goes like this:

with the help of the hormone, the permeability of the cell membrane is stabilized, and glucose easily penetrates through it;
Insulin plays a role in facilitating the transfer of glucose to glycogen storage in muscle tissue and the liver;
the hormone helps in the breakdown of sugar;
inhibits the activity of enzymes that break down glycogen and fat.

A decrease in the body's own production of insulin leads to the formation of type I diabetes mellitus in a person. During this process, beta cells, in which insulin is properly metabolized, are destroyed without the possibility of restoration. Patients with this type of diabetes require regular administration of industrially synthesized insulin.

If the hormone is produced in an optimal volume, and cell receptors lose sensitivity to it, this signals the formation of type 2 diabetes mellitus. Insulin therapy for this disease is not used in the initial stages. As the severity of the disease increases, the endocrinologist prescribes insulin therapy to reduce the level of stress on the organ.

Glucagon

Glucagon – breaks down glycogen in the liver

The peptide is produced by A-cells of the organ islets and cells of the upper digestive tract. Glucagon production is stopped due to an increase in the level of free calcium inside the cell, which can be observed, for example, when exposed to glucose.

Glucagon is the main antagonist of insulin, which is especially pronounced when there is a deficiency of the latter.

Glucagon affects the liver, where it promotes the breakdown of glycogen, causing an accelerated increase in the concentration of sugar in the bloodstream. Under the influence of the hormone, the breakdown of proteins and fats is stimulated, and the production of proteins and lipids is stopped.

Somatostatin

The polypeptide produced in the D-cells of the islets is characterized by reducing the synthesis of insulin, glucagon, and growth hormone.

Vasointense peptide

The hormone is produced by a small number of D1 cells. Vasoactive intestinal polypeptide (VIP) is built using more than twenty amino acids. Normally, the body contains it in the small intestine and organs of the peripheral and central nervous systems.

VIP functions:

increases the activity of blood flow in, activates motor skills;
reduces the rate of release of hydrochloric acid by parietal cells;
triggers the production of pepsinogen, an enzyme that is a component of gastric juice and breaks down proteins.

Due to an increase in the number of D1 cells that synthesize intestinal polypeptide, a hormonal tumor forms in the organ. Such a neoplasm is cancerous in 50% of cases.

Pancreatic polypeptide

Horn, stabilizing the activity of the body, will stop the activity of the pancreas and activate the synthesis of gastric juice. If the structure of the organ is defective, the polypeptide will not be produced in the required volume.

Amylin

When describing the functions and effects of amylin on organs and systems, it is important to note the following:

the hormone prevents excess glucose from entering the blood;
reduces appetite, promoting a feeling of satiety, reduces the size of food portions consumed;
supports the secretion of an optimal ratio of digestive enzymes that work to reduce the rate of growth of glucose levels in the bloodstream.

In addition, amylin slows down the production of glucagon during food intake.

Lipocaine, kallikrein, vagotonin

Lipocaine triggers the metabolism of phospholipids and the combination of fatty acids with oxygen in the liver. The substance increases the activity of lipotropic compounds in order to prevent fatty liver degeneration.

Although kallikrein is produced in the gland, it is not activated in the organ. When the substance passes into the duodenum, it is activated and has an effect: it reduces blood pressure and blood sugar levels.

Vagotonin promotes the formation of blood cells and lowers the amount of glucose in the blood, as it slows down the decomposition of glycogen in the liver and muscle tissue.

Centropnein and gastrin

Gastrin is synthesized by gland cells and the gastric mucosa. It is a hormone-like substance that increases the acidity of digestive juice, triggers the synthesis of pepsin, and stabilizes the course of digestion.

Centropnein is a protein substance that activates the respiratory center and increases the diameter of the bronchi. Centropnein promotes the interaction of iron-containing protein and oxygen.

Gastrin

Gastrin promotes the formation of hydrochloric acid and increases the volume of pepsin synthesis by stomach cells. This has a good effect on the functioning of the gastrointestinal tract.

Gastrin may reduce the rate of bowel movements. With this, the timely effect of hydrochloric acid and pepsin on the food mass is ensured.

Gastrin has the ability to regulate carbohydrate metabolism, activate the growth of secretin production and a number of other hormones.

Hormone preparations

Pancreatic hormone preparations have traditionally been described for the purpose of considering treatment regimens for diabetes mellitus.

The problem of pathology is a violation in the ability of glucose to enter the body's cells. As a result, there is an excess of sugar in the bloodstream, and an extremely acute deficiency of this substance occurs in the cells.

A serious disruption occurs in the energy supply of cells and metabolic processes. Treatment with drugs has the main goal of stopping the described problem.

Classification of antidiabetic drugs

Insulin medications are prescribed by the doctor individually to each patient.

Insulin medicines:

monosulin;
Insulin-semilong suspension;
Insulin-long suspension;
Insulin-ultralong suspension.

The dosage of the listed drugs is measured in units. The dose calculation is based on the concentration of glucose in the bloodstream, taking into account that 1 unit of the drug stimulates the removal of 4 g of glucose from the blood.

Supphonyl urea derivatives:

tolbutamide (Butamide);
chlorpropamide;
glibenclamide (Maninil);
gliclazide (Diabeton);
glipizide.

Principle of influence:

inhibit ATP-dependent potassium channels in the beta cells of the pancreatic gland;
depolarization of the membranes of these cells;
triggering of voltage-dependent ion channels;
penetration of calcium into the cell;
calcium increases the release of insulin into the bloodstream.

Biguanide derivatives:

Metformin (Siofor)

Tablets Diabeton

Principle of action: increases the uptake of sugar by the cells of skeletal muscle tissue and increases its anaerobic glycolysis.

Drugs that reduce cell resistance to the hormone: pioglitazone.

Mechanism of action: at the DNA level, it increases the production of proteins that increase tissue perception of the hormone.

Acarbose

Mechanism of action: reduces the amount of glucose absorbed by the intestines and entering the body with food.

Until recently, therapy for patients with diabetes used drugs obtained from animal hormones or from modified animal insulin, in which a single amino acid was changed.

Progress in the development of the pharmaceutical industry has led to the ability to develop medicines with a high level of quality using genetic engineering tools. Insulins obtained by this method are hypoallergenic; to effectively suppress the signs of diabetes, a smaller dose of the drug is used.

How to take medications correctly

There are a number of rules that are important to follow when taking medications:

The medicine is prescribed by a doctor, indicating the individual dosage and duration of therapy.
During the period of treatment, it is recommended to follow a diet: exclude alcoholic beverages, fatty foods, fried foods, and sweet confectionery products.
It is important to check that the prescribed medicine has the same dosage as indicated in the prescription. It is forbidden to split pills or increase the dosage yourself.
If side effects occur or there is no result, you must notify your doctor.

Contraindications and side effects

In medicine, human insulins developed by genetic engineering methods and highly purified pork insulins are used. Because of this, side effects of insulin therapy are observed relatively infrequently.

Allergic reactions and pathologies of adipose tissue at the injection site are possible.

When excessively high doses of insulin enter the body or with limited administration of nutritional carbohydrates, increased hypoglycemia may occur. Its severe variant is hypoglycemic coma with loss of consciousness, convulsions, insufficiency in the functioning of the heart and blood vessels, and vascular insufficiency.

Symptoms of hypoglycemia

During this condition, the patient must be administered intravenously a 40% glucose solution in the amount of 20-40 (not more than 100) ml.

Since hormone preparations are used for the rest of life, it is important to remember that their hypoglycemic potential can be affected by various medications.

Increase the hypoglycemic effect of the hormone: alpha-blockers, P-blockers, tetracycline antibiotics, salicylates, parasympatholytic drugs, drugs that imitate testosterone and dihydrotestosterone, antimicrobial agents sulfonamides.

The main hormones of the pancreas:

· insulin (normal blood concentration in a healthy person is 3-25 µU/ml, in children 3-20 µU/ml, in pregnant and elderly people 6-27 µU/ml);

glucagon (plasma concentration 27-120 pg/ml);

c-peptide (normal level 0.5-3.0 ng/ml);

· pancreatic polypeptide (fasting serum PP level 80 pg/ml);

gastrin (normal range from 0 to 200 pg/ml in blood serum);

· amylin;

The main function of insulin in the body is to lower blood sugar levels. This occurs due to simultaneous action in several directions. Insulin stops the formation of glucose in the liver, increasing the amount of sugar absorbed by the tissues of our body due to the permeability of cell membranes. And at the same time, this hormone stops the breakdown of glucagon, which is part of a polymer chain consisting of glucose molecules.

The alpha cells of the islets of Langerhans are responsible for the production of glucagon. Glucagon is responsible for increasing the amount of glucose in the bloodstream by stimulating its production in the liver. In addition, glucagon promotes the breakdown of lipids in adipose tissue.

A growth hormone somatotropin increases alpha cell activity. In contrast, the delta cell hormone somatostatin inhibits the formation and secretion of glucagon, since it blocks the entry of Ca ions into alpha cells, which are necessary for the formation and secretion of glucagon.

Physiological significance lipocaine. It promotes the utilization of fats by stimulating the formation of lipids and the oxidation of fatty acids in the liver, it prevents fatty degeneration of the liver.

Functions vagotonin– increased tone of the vagus nerves, increased activity.

Functions centropnein– stimulation of the respiratory center, promoting relaxation of bronchial smooth muscles, increasing the ability of hemoglobin to bind oxygen, improving oxygen transport.

The human pancreas, mainly in its caudal part, contains approximately 2 million islets of Langerhans, constituting 1% of its mass. The islets are composed of alpha, beta and delta cells that produce glucagon, insulin and somatostatin (inhibiting the secretion of growth hormone), respectively.

Insulin Normally, it is the main regulator of blood glucose levels. Even a slight increase in blood glucose causes insulin secretion and stimulates its further synthesis by beta cells.

CLASSIFICATION OF INSULIN PREPARATIONS

All insulin preparations produced by global pharmaceutical companies differ mainly in three main characteristics:

1) by origin;

2) by the speed of onset of effects and their duration;

3) according to the method of purification and the degree of purity of the preparations.

I. By origin they distinguish:

a) natural (biosynthetic), natural, insulin preparations made from the pancreas of cattle, for example, insulin tape GPP, ultralente MS and more often pigs (for example, actrapid, insulinrap SPP, monotard MS, semilente, etc.);

b) synthetic or, more precisely, species-specific, human insulins. These drugs are obtained using genetic engineering methods using DNA-recombinant technology, and therefore they are most often called DNA-recombinant insulin preparations (actrapid NM, homophane, isophane NM, humulin, ultratard NM, monotard NM, etc.).

III. Based on the speed of onset of effects and their duration, they are distinguished:

a) fast-acting, short-acting drugs (Actrapid, Actrapid MS, Actrapid NM, Insulrap, Homorap 40, Insuman Rapid, etc.). The onset of action of these drugs is after 15-30 minutes, the duration of action is 6-8 hours;

b) drugs of medium duration of action (onset of action after 1-2 hours, total duration of effect - 12-16 hours); - semilente MS; - humulin N, humulin lente, homophane; - tape, tape MS, monotard MS (2-4 hours and 20-24 hours, respectively); - iletin I NPH, iletin II NPH; - insulong SPP, insulin lente GPP, SPP, etc.

c) medium-duration drugs mixed with short-acting insulin: (onset of action 30 minutes; duration - from 10 to 24 hours);

Aktrafan NM;

Humulin M-1; M-2; M-3; M-4 (duration of action up to 12-16 hours);

Insuman com. 15/85; 25/75; 50/50 (valid for 10-16 hours).

d) long-acting drugs:

Ultralente, ultralente MS, ultralente NM (up to 28 hours);

Insulin superlente SPP (up to 28 hours);

Humulin ultralente, ultratard NM (up to 24-28 hours).

ACTRAPID, obtained from the beta cells of porcine pancreatic islets, is produced as an official drug in 10 ml bottles, most often with an activity of 40 units per 1 ml. It is administered parenterally, most often under the skin. This drug has a rapid sugar-lowering effect. The effect develops after 15-20 minutes, and the peak of action is observed after 2-4 hours. The total duration of the hypoglycemic effect is 6-8 hours in adults, and up to 8-10 hours in children.

Advantages of rapid short-acting insulin preparations (actrapide):

1) act quickly;

2) give a physiological peak concentration in the blood;

3) act for a short time.

Indications for the use of rapid short-acting insulin preparations:

1. Treatment of patients with insulin-dependent diabetes mellitus. The drug is injected under the skin.

2. For the most severe forms of non-insulin-dependent diabetes mellitus in adults.

3. For diabetic (hyperglycemic) coma. In this case, the drugs are administered both under the skin and into a vein.

ANTIDIABETIC (HYPOGLYCEMIC) ORAL DRUGS

Stimulating endogenous insulin secretion (sulfonylureas):

1. First generation drugs:

a) chlorpropamide (syn.: diabinez, catanil, etc.);

b) bukarban (syn.: oranil, etc.);

c) butamide (syn.: orabet, etc.);

d) tolinase.

2. Second generation drugs:

a) glibenclamide (syn.: maninil, oramide, etc.);

b) glipizide (syn.: minidiab, glibinez);

c) gliquidone (syn.: glyurenorm);

d) gliclazide (syn.: Predian, Diabeton).

II. Affecting the metabolism and absorption of glucose (biguanides):

a) buformin (glybutide, adebit, sibin retard, dimethyl biguanide);

b) metformin (gliformin). III. Slowing glucose absorption:

a) glucobay (acarbose);

b) guar (guar gum).

BUTAMID (Butamidum; issued in tablets of 0.25 and 0.5) is a first-generation drug, a sulfonylurea derivative. The mechanism of its action is associated with a stimulating effect on beta cells of the pancreas and their increased secretion of insulin. The onset of action is 30 minutes, its duration is 12 hours. The drug is prescribed 1-2 times a day. Butamide is excreted by the kidneys. This drug is well tolerated.

Side effects:

1. Dyspepsia. 2. Allergies. 3. Leukocytopenia, thrombocytopenia. 4. Hepatotoxicity. 5. Tolerance may develop.

BIGUANIDES are derivatives of guanidine. The two most famous drugs are:

Buformin (glybutide, adebit);

Metformin.

GLIBUTID (Glibutidum; issue in tablets 0.05)

1) promotes the absorption of glucose by muscles in which lactic acid accumulates; 2) increases lipolysis; 3) reduces appetite and body weight; 4) normalizes protein metabolism (in this regard, the drug is prescribed for excess weight).

They are most often used in patients with diabetes mellitus-II, accompanied by obesity.