PREPARATIONS FOR HORMONES AND THEIR ANALOGUES. Part 1

Hormones are chemical substances that are biologically active substances produced by the endocrine glands, entering the bloodstream and acting on target organs or tissues.

The term "hormone" comes from the Greek word "hormao" - to excite, force, induce activity. Currently, it has been possible to decipher the structure of most hormones and synthesize them.

According to the chemical structure, hormonal drugs, like hormones, are classified:

a) hormones of protein and peptide structure (preparations of hormones of the hypothalamus, pituitary, parathyroid and pancreas, calcitonin);

b) derivatives of amino acids (iodine-containing derivatives of thyronine - preparations of thyroid hormones, adrenal medulla);

c) steroid compounds (preparations of hormones of the adrenal cortex and gonads).

In general, endocrinology today studies more than 100 chemicals synthesized in various organs and systems of the body by specialized cells.

There are the following types of hormonal pharmacotherapy:

1) replacement therapy (for example, the administration of insulin to patients with diabetes mellitus);

2) inhibitory, depressive therapy in order to suppress the production of own hormones in excess of them (for example, with thyrotoxicosis);

3) symptomatic therapy, when the patient has no hormonal disorders in principle, and the doctor prescribes hormones for other indications - in severe rheumatism (as anti-inflammatory drugs), severe inflammatory diseases of the eyes, skin, allergic diseases, etc.

REGULATION OF HORMONE SYNTHESIS IN THE BODY

The endocrine system, together with the central nervous system and the immune system, and under their influence, regulate the homeostasis of the body. The interaction of the central nervous system and the endocrine system is carried out through the hypothalamus, the neurosecretory cells of which (reacting to acetylcholine, norepinephrine, serotonin, dopamine) synthesize and secrete various releasing factors and their inhibitors, the so-called liberins and statins, which enhance or block the release of the corresponding tropic hormones from the anterior lobe pituitary gland (i.e. adenohypophysis). Thus, the releasing factors of the hypothalamus, acting on the adenohypophysis, change the synthesis and release of hormones of the latter. In turn, the hormones of the anterior pituitary gland stimulate the synthesis and release of hormones from target organs.

In the adenohypophysis (anterior lobe), the following hormones are synthesized, respectively:

Adrenocorticotropic (ACTH);

Growth hormone (STH);

Follicle-stimulating and luteotropic hormones (FSH, LTH);

Thyroid stimulating hormone (TSH).

In the absence of hormones from the adenohypophysis, the target glands not only stop functioning, but also atrophy. On the contrary, with an increase in the level of hormones secreted by the target glands in the blood, the rate of synthesis of releasing factors in the hypothalamus changes and the sensitivity of the pituitary gland to them decreases, which leads to a decrease in the secretion of the corresponding tropic hormones of the adenohypophysis. On the other hand, with a decrease in the level of hormones of target glands in the blood plasma, the release of the releasing factor and the corresponding tropic hormone increases. Thus, the production of hormones is regulated according to the principle of feedback: the lower the concentration of hormones of target glands in the blood, the greater the production of hormones-regulators of the hypothalamus and hormones of the anterior pituitary gland. It is very important to remember this when carrying out hormonal therapy, since hormonal drugs in the patient's body inhibit the synthesis of his own hormones. In this regard, when prescribing hormonal drugs, a full assessment of the patient's condition should be made in order to avoid irreparable mistakes.

MECHANISM OF ACTION OF HORMONES (PREPARATIONS)

Hormones, depending on their chemical structure, can have an effect on the genetic material of the cell (on the DNA of the nucleus), or on specific receptors located on the surface of the cell, on its membrane, where they disrupt the activity of adenylate cyclase or change the permeability of the cell for small molecules (glucose, calcium), which leads to a change in the functional state of cells.

After binding to the receptor, steroid hormones migrate to the nucleus, bind to specific regions of chromatin and, thus, increase the rate of synthesis of specific mRNA into the cytoplasm, where the rate of synthesis of a specific protein, for example, an enzyme, increases.

Catecholamines, polypeptides, protein hormones change the activity of adenylate cyclase, increase the content of cAMP, as a result of which the activity of enzymes changes, the membrane permeability of cells, etc.

PREPARATIONS FOR PANCREAS HORMONES

The human pancreas, mainly in the tail part, contains about 2 million islets of Langerhans, accounting for 1% of its mass. The islets are composed of alpha, beta, and delta cells, which produce glucagon, insulin, and somatostatin (which inhibits growth hormone secretion), respectively.

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

Insulin was first singled out in 1921 by Banting, Best - for which they received the Nobel Prize in 1923. Insulin 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 the secretion of insulin and stimulates its further synthesis by beta cells.

The mechanism of action of insulin is associated with the fact that the hubbub increases the absorption of glucose by tissues and promotes its conversion into glycogen. Insulin, increasing the permeability of cell membranes for glucose and lowering 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.

The cells are very well 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, the glycogen stores are also striated muscle cells.

With a lack of insulin, glucose will not be adequately absorbed by the tissues, which will be expressed by hyperglycemia, and with very high numbers of glucose in the blood (more than 180 mg / l) and glucosuria (sugar in the urine). Hence the Latin name for diabetes mellitus: "Diabetеs mellitus" (diabetes mellitus).

The need for glucose in tissues is different. In a number of tissues - the brain, cells of the optic epithelium, the seminal epithelium - the formation of energy occurs only due to glucose. In tissues other than glucose, fatty acids can be used for energy production.

In diabetes mellitus, a situation arises in which, in the midst of "abundance" (hyperglycemia), cells experience "hunger".

In the patient's body, in addition to carbohydrate metabolism, other types of metabolism are also perverted. When insulin is deficient, there is a negative nitrogen balance when amino acids are predominantly used in gluconeogenesis, this wasteful conversion of amino acids into glucose, where 56 g of glucose is formed from 100 g of protein.

Fat metabolism is also impaired, and this is primarily associated with an increase in the level of free fatty acids (FFA) in the blood, 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 disturbance in diabetes mellitus). In addition, under these conditions, cell resistance to insulin develops.

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

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

1. Insulin-dependent diabetes mellitus (formerly called juvenile) - IDDM (DM-I) develops as a result of progressive death of beta cells, and therefore is associated with insufficient insulin secretion. This type debuts before the age of 30 and is associated with a multifactorial type 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 antigens and

DR3 are at greatest risk of developing insulin-dependent diabetes mellitus.

The proportion of patients with insulin-dependent diabetes mellitus is 15-20% of the total.

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

The development of this type of diabetes mellitus is not associated with the main human 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 beta-cells ability to secrete a compensatory amount of insulin. The proportion of patients with this form of diabetes is 80-85%.

In addition to the two main types, there are:

3. Diabetes mellitus associated with malnutrition.

4. Secondary, symptomatic diabetes mellitus (endocrine genesis: goiter, acromegaly, diseases of the pancreas).

5. Diabetes of pregnant women.

Currently, a certain methodology has developed, that is, a system of principles and views on the treatment of patients with diabetes mellitus, the key ones 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 principles of treatment, the following three traditional components remain the main methods of therapy for patients with diabetes mellitus:

2) insulin preparations for patients with insulin-dependent diabetes mellitus;

3) oral hypoglycemic agents for patients with non-insulin dependent diabetes mellitus.

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

I. Insulin preparations.

II. Synthetic oral (tableted) antidiabetic agents.

The pancreas produces two hormones: glucagon(α-cells) and insulin(β-cells). The main role of glucagon is to increase the concentration of glucose in the blood. In contrast, one of the main functions of insulin is to lower the concentration of glucose in the blood.

Pancreatic hormone preparations are traditionally considered in the context of therapy for a very serious and common disease - diabetes mellitus. The problem of the etiology and pathogenesis of diabetes mellitus is very complex and multifaceted, therefore, here we will pay attention only to one of the key links in the pathogenesis of this pathology: a violation of the ability of glucose to penetrate into cells. As a result, an excess of glucose appears in the blood, and the cells experience its most severe deficiency. The energy supply of cells suffers, the metabolism of carbohydrates is impaired. The medical treatment of diabetes mellitus is aimed precisely at eliminating this situation.

Physiological role of insulin

The triggering factor for insulin secretion is an increase in the concentration of glucose in the blood. In this case, glucose penetrates into the β-cells of the pancreas, where it breaks down with the formation of molecules of adenosine triphosphoric acid (ATP). This leads to inhibition of ATP-dependent potassium channels with subsequent impairment of the release of potassium ions from the cell. Depolarization of the cell membrane occurs, during which voltage-gated calcium channels open. Calcium ions enter the cell and, being a physiological stimulant of exocytosis, activate the secretion of insulin into the blood.

Once in the blood, insulin binds to specific membrane receptors, forming a transport complex, in the form of which it penetrates into the cell. There, through a cascade of biochemical reactions, it activates the membrane transporters GLUT-4, designed to transfer glucose molecules from the blood to the cell. Glucose trapped in the cell is utilized. In addition, in hepatocytes, insulin activates the enzyme glycogen synthetase and inhibits phosphorylase.

As a result, glucose is consumed for the synthesis of glycogen, and its concentration in the blood decreases. In parallel, hexakinase is activated, which activates the formation of glucose-6-phosphate from glucose. The latter is metabolized in the reactions of the Krebs cycle. The consequence of the described processes is a decrease in the concentration of glucose in the blood. In addition, insulin blocks the enzymes of gluconeogenesis (the process of forming glucose from non-carbohydrate products), which also helps to reduce plasma glucose levels.

Classification of antidiabetic drugs

Insulin preparations ⁎ monosuinsulin; ⁎ suspension of insulin-semilong; ⁎ suspension of insulin-long; ⁎ suspension of insulin-ultralong, etc. Insulin preparations are dosed in units. Doses are calculated based on the concentration of glucose in the blood plasma, taking into account the fact that 1 U of insulin promotes the utilization of 4 g of glucose. Supfonylurea derivatives ⁎ tolbutamide (butamide); ⁎ chlorpropamide; ⁎ glibenclamide (maninil); ⁎ gliclazide (diabeton); ⁎ glipizide, etc. Mechanism of action: block ATP-dependent potassium channels in β-cells of the pancreas depolarization of cell membranes ➞ activation of voltage-gated calcium channels ➞ calcium entry into the cell ➞ calcium, being a natural stimulant of exocytosis, increases the release of insulin into the blood. Biguanide derivatives ⁎ metformin (Siofor). Mechanism of action: increases the uptake of glucose by cells of skeletal muscle and enhances its anaerobic glycolysis. Drugs that reduce tissue resistance to insulin: ⁎ pioglitazone. Mechanism of action: at the genetic level, it increases the synthesis of proteins that increase the sensitivity of tissues to insulin. Acarbose Mechanism of action: reduces absorption of glucose from food in the intestine.

Sources:
1. Lectures on pharmacology for higher medical and pharmaceutical education / V.М. Bryukhanov, J.F. Zverev, V.V. Lampatov, A.Yu. Zharikov, O.S. Talalaeva - Barnaul: Spektr Publishing House, 2014.
2. Pharmacology with recipe / Gayevy M.D., Petrov V.I., Gayevaya L.M., Davydov V.S., - M .: ICC March, 2007.

The pancreas is the most important digestive gland that produces a large number of enzymes that carry out the assimilation of proteins, lipids, carbohydrates. It is also a gland that synthesizes insulin and one of the suppressing hormones - glucagon.When the pancreas cannot cope with its functions, it is necessary to take pancreatic hormones. What are the indications and contraindications for taking these drugs?

The pancreas is an important digestive organ

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

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

Its exocrine area has classic secretory sections, the duct part, where the formation of pancreatic juice is performed, which is necessary for the digestion of food, the decomposition of proteins, lipids, and carbohydrates.

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

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

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

In terms of its mass, the pancreatic gland of an adult is within the range of 70-80 g.

Pancreatic hormones and their functions

The body performs external and intrasecretory work

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

Insulin is produced by β-cells of the islets of Langerhans, which are concentrated mainly in the tail of the gland. Insulin is responsible for getting glucose into cells, stimulating glucose uptake and lowering blood sugar levels.

The hormone glucagon, on the other hand, raises the amount of glucose, arresting hypoglycemia. The hormone is synthesized by the 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 appearance 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 PN cells. Delta cells produce ghrelin, an appetite hormone. PP cells synthesize a pancreatic polypeptide that stabilizes the secretory function of the gland.

The pancreas produces hormones. All of them are necessary to maintain human life. Further on the hormones of the gland in more detail.

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 of the organ and are called islets of Langerhans.

Insulin controls blood glucose levels

Insulin is primarily responsible for controlling blood glucose levels. This process is done like this:

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

A decrease in the production of insulin by the body's own forces leads to the formation of type I diabetes mellitus in a person. In this process, beta cells are destroyed without the possibility of recovery, in which, with healthy carbohydrate metabolism, insulin is destroyed. Patients with this type of diabetes need regular administration of synthesized insulin.

If the hormone is produced in an optimal volume, and the receptors of the cells lose sensitivity to it, this signals the formation of type 2 diabetes mellitus. Insulin therapy for this disease at the initial stages is not used. With an increase in the severity of the disease, an 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 the A-cells of the islets of the organ and the cells of the upper part of the digestive tract. The production of glucagon 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 with a lack of the latter.

Glucagon has an effect on 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 islet D-cells is characterized by the fact that it reduces the synthesis of insulin, glucagon, growth hormone.

Vaso-intensive peptide

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

VIP functions:

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

Due to the increase in the number of D1 cells synthesizing the intestinal polypeptide, a hormonal tumor is formed in the organ. Such a neoplasm in 50% of cases is oncological.

Pancreatic polypeptide

By mountain stabilizing the activity of the body, it 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 proper volume.

Amilin

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

• the hormone prevents excess glucose from entering the blood;
• reduces appetite, contributing to the feeling of satiety, reduces the size of the portion of food consumed;
• supports the secretion of an optimal ratio of digestive enzymes that work to reduce the rate of increase in 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 degeneration of the liver.

Kallikrein, although produced in the gland, is not activated in the organ. When the substance passes into the duodenum, it is activated and acts: it lowers blood pressure and blood sugar levels.

Vagotonin promotes the formation of blood cells, lowering 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 the cells of the gland and the gastric mucosa. It is a hormone-like substance that increases the acidity of the 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, increases the volume of pepsin synthesis by stomach cells. This is well reflected in the course of the gastrointestinal tract.

Gastrin can decrease the rate of emptying. With the help of this, the effect of hydrochloric acid and pepsin on the food mass should be ensured in time.

Gastrinimines have the ability to regulate carbohydrate metabolism, activate the growth in the production of secretin and a number of other hormones.

Hormone preparations

Pancreatic hormone preparations have traditionally been described for the purpose of considering a diabetes regimen.

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

There is a serious failure in the energy supply of cells and metabolic processes. Drug treatment has the main goal of stopping the described problem.

Classification of antidiabetic drugs

Insulin preparations are prescribed by the doctor individually for each patient.

Insulin medicines:

• monosuinsulin;
• suspension of Insulin-Semilong;
• suspension of Insulin-Long;
• suspension of Insulin-ultralong.

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

Supfonil urea derivatives:

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

Impact principle:

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

Biguanide derivatives:

• Metformin (Siofor)

Diabeton tablets

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

Drugs that reduce the resistance of cells to the hormone: pioglitazone.

Mechanism of action: at the DNA level, it increases the production of proteins that contribute to an increase in the perception of the hormone by tissues

• Acarbose

Mechanism of action: reduces the amount of glucose absorbed by the intestine that enters the body with food.

Until recently, the therapy of patients with diabetes used funds derived from animal hormones or from modified animal insulin, in which one amino acid was changed.

Advances in the development of the pharmaceutical industry have led to the ability to develop high quality medicines using genetic engineering tools. The insulins obtained by this method are hypoallergenic; a smaller dose of the drug is used to effectively suppress the signs of diabetes.

How to take drugs correctly

There are a number of rules that are important to follow at the time of taking drugs:

1. The medicinal product is prescribed by the doctor, indicates the individual dosage and duration of therapy.
2. For the period of treatment, it is recommended to follow a diet: exclude alcoholic beverages, fatty foods, fried foods, sweet confectionery products.
3. It is important to check that the prescribed medication has the same dosage as indicated in the prescription. It is forbidden to share pills, as well as to increase the dosage with your own hands.
4. In case of side effects or no result, it is necessary to notify the doctor.

Contraindications and side effects

In medicine, genetically engineered human insulins and highly purified pork insulins are used. Because of this, the side effects of insulin therapy are relatively rare.

Allergic reactions, pathologies of adipose tissue at the injection site are likely.

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

Symptoms of hypoglycemia

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

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

Increase the hypoglycemic effect of the hormone: alpha-blockers, β-blockers, antibiotics of the tetracyclines group, salicylates, parasympatholytic drug, drugs that mimic testosterone and dihydrotestosterone, antimicrobial agents sulfonamides.

Book: Lecture notes Pharmacology

10.4. Pancreatic hormone preparations, insulin preparations.

In the regulation of metabolic processes in the body, hormones of the pancreas are of great importance. In the cells of the pancreatic islets, insulin is synthesized, which has a hypoglycemic effect, in a-cells, the counterinsular hormone glucagon is produced, which has a hyperglycemic effect. In addition, the L cells of the pancreas produce somatostatin.

The principles of insulin production were developed by L.V. Sobolev (1901), who, in an experiment on the glands of newborn calves (they still do not have trypsin, they decompose insulin), showed that pancreatic islets (Langerhans) are the substrate for the internal secretion of the pancreas. In 1921, Canadian scientists F.G.Banting and Ch. H. Best isolated pure insulin and developed a method for its industrial production. 33 years later, Sanger and his co-workers deciphered the primary structure of bovine insulin, for which he received the Nobel Prize.

Insulin from the pancreas of slaughter animals is used as a drug. Chemically close to human insulin is a preparation from the pancreas of pigs (it differs only in one amino acid). Recently, preparations of human insulin have been created, and significant advances have been made in the field of biotechnological synthesis of human insulin using genetic engineering. This is a great achievement in molecular biology, molecular genetics and endocrinology, since homologous human insulin, unlike a heterologous animal, does not cause a negative immunological reaction.

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. In the physiological regulation of insulin synthesis, the dominant role is played by the concentration of glucose in the blood. Penetrating into P-cells, glucose is metabolized and promotes an increase in the intracellular ATP content. The latter, by blocking ATP-dependent potassium channels, causes depolarization of the cell membrane. This facilitates the penetration of calcium ions into P-cells (through voltage-gated calcium channels that have opened) and the release of insulin by exocytosis. In addition, the secretion of insulin is influenced by amino acids, free fatty acids, glycogen, and secretin, electrolytes (especially C2 +), the autonomic nervous system (the sympathetic non- and moat system has an inhibitory effect, and the parasympathetic one has a stimulating effect).

Pharmacodynamics. The action of insulin is aimed at the exchange of carbohydrates, proteins, and fats, minerals. The main thing in the action of insulin is its regulating effect on the metabolism of carbohydrates, a decrease in the level of glucose in the blood, and this is achieved by the fact that insulin promotes the active transport of glucose and other hexoses, as well as pentoses through cell membranes and their utilization by the liver, muscle and adipose tissues. Insulin stimulates glycolysis, induces the synthesis of enzymes I glucokinase, phosphofructokinase and pyruvate kinase, stimulates pentose phosphate I cycle, activating glucose phosphate dehydrogenase, increases glycogen synthesis, activating glycogen synthetase, the activity of which is reduced in patients with diabetes mellitus. On the other hand, the hormone inhibits 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, and where it regulates the transport of mRNA from the nucleus and cytoplasm. Insulin stimulates biosin - And theses of nucleic acids, proteins. In parallel - but with the activation of anabolic processes AND insulin inhibits the catabolic reactions of the breakdown of protein molecules. It also stimulates the processes of lipogenesis, the formation of glycerol and its input to lipids. Along with the synthesis of triglycerides, insulin activates the synthesis of phospholipids in fat cells (phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and cardiolipin), also stimulates the biosynthesis of cholesterol, which is necessary, like phospholipids and some glycoproteins, to build cell membranes.

For an insufficient amount of insulin, lipogenesis is suppressed, lipolysis, lipid peroxidation increase, the level of ketone bodies in the blood and urine increases. Due to the decreased activity of lipoprotein in the blood, the concentration of P-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 has not been fully disclosed. The first link of insulin action is binding to specific receptors of the plasma membrane of target cells, primarily in the liver, adipose tissue and muscles.

Insulin combines with the o-subunit of the receptor (contains the main insulin "ulcer domain). At the same time, the kinase activity of the P-subunit of the receptor (tyrosine kinase) is stimulated, it is autophosphorized. A complex" insulin + receptor "is created, which by endocytosis penetrates into the cell, where and the cellular mechanisms of the hormone action are triggered.

The cellular mechanisms of insulin action involve not only secondary mediators: cAMP, Ca2 +, calcium-calmodulin complex, inositol triphosphate, diacylglycerol, but also fructose-2,6-diphosphate, 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-diphosphate under the influence of insulin that promotes the utilization of glucose from the blood, 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 diabetes mellitus, peripheral hyper-insulinism.

Insulin receptors exist not only on the plasma membrane, but also in the membrane components of such internal organelles as the nucleus, the endoplasmic reticulum, and the Golga complex.

The administration of insulin to patients with diabetes mellitus helps to reduce the level of glucose in the blood and the accumulation of glycogen in tissues, reduce glycosuria and associated polyuria, polydipsia.

Due to the normalization of protein metabolism, the concentration of nitrogen compounds in the urine decreases, and due to the normalization of fat metabolism in the blood and urine, ketone bodies disappear - acetone, acetocet and oxybutyric acids. Weight loss stops and excessive hunger (bulimia) disappears. The detoxification function of the liver increases, the body's resistance to infections increases.

Classification. Modern insulin preparations differ in speed and duration of action. they can be divided into the following groups:

1. Preparations of short-acting insulin, or simple insulins (monoinsulin MK ak-trapid, humulin, homorap, etc.) A decrease in blood glucose levels after their administration begins in 15-30 minutes, the maximum effect is observed after 1.5-2 hours, the action lasts up to 6-8 hours.

2. Long-acting insulin preparations:

a) medium duration (beginning after 1.5-2 hours, duration 8-12 hours) - suspension-insulin-semilente, B-insulin;

b) long-acting (onset after 6-8 hours, duration 20-30 hours) - suspension-insulin-ultralente. Extended-release drugs are administered subcutaneously or intramuscularly.

3. Combined preparations containing insulin of the 1st and 2nd groups, for example

treasure of 25% simple insulin and 75% ultralente insulin.

Some drugs are available in syringe tubes.

Insulin preparations are dosed in units of action (IU). The dose of insulin for each patient is selected individually in a hospital under constant monitoring of the level of glucose in the blood and urine after administration of the drug (1 U of the hormone for 4-5 g of glucose excreted in the urine; a more accurate calculation method is taking into account the level of glycemia). The patient is transferred to a diet that limits the amount of easily digestible carbohydrates.

Depending on the source of production, insulin is distinguished, isolated from the pancreas of pigs (C), cattle (G), human (H - hominis), and also synthesized by genetic engineering methods.

According to the degree of purification, insulins of animal origin are divided into mono-components (MP, foreign - MP) and monocomponent (MC, foreign - MS).

Indications. Insulin therapy is absolutely indicated for patients with insulin-dependent diabetes mellitus. it should be started when diet, weight control, physical activity, and oral antidiabetic drugs do not provide the desired effect. Insulin is used for diabetic coma, as well as for patients with diabetes of any type, if the disease is accompanied by complications (ketoacidosis, infection, gangrene, etc.); for better absorption of glucose in diseases of the heart, liver, surgical operations, in the postoperative period (5 units each); to improve the nutrition of patients exhausted by a prolonged illness; rarely for shock therapy - in psychiatric practice for some forms of schizophrenia; as part of a polarizing mixture for heart disease.

Contraindications: diseases with hypoglycemia, hepatitis, cirrhosis of the liver, pancreatitis, glomerulonephritis, nephrolithiasis, gastric ulcer and duodenal ulcer, decompensated heart defects; for drugs with prolonged action - coma, infectious diseases, during the period of surgical treatment of patients with diabetes mellitus.

Side effects: painful injections, local inflammatory reactions (infiltration), allergic reactions.

In case of an overdose of insulin, hypoglycemia may occur. Symptoms of hypoglycemia: anxiety, general weakness, cold sweat, trembling limbs. A significant decrease in blood glucose leads to dysfunction of the brain, the development of coma, seizures and even death. To prevent hypoglycemia, people with diabetes should have a few lumps of sugar with them. If, after taking sugar, the symptoms of hypoglycemia do not disappear, an urgent need to intravenously inject 20-40 ml of a 40% glucose solution, subcutaneously 0.5 ml of a 0.1% solution of adrenaline. In cases of significant hypoglycemia due to the action of prolonged insulin preparations, it is more difficult to remove patients from this state than with hypoglycemia caused by short-acting insulin preparations. The presence of protamine protein in some drugs with prolonged action explains the rather frequent cases of allergic reactions. However, injections of long-acting insulin preparations are less painful due to the higher pH of these drugs.

1.	Lecture notes Pharmacology
2.	History of drug science and pharmacology
3.	1.2. Drug-related factors.
4.	1.3. Body-related factors
5.	1.4. The influence of the environment on the interaction of the body and the medicinal substance.
6.	1.5. Pharmacokinetics.
7.	1.5.1. The main concepts of pharmacokinetics.
8.	1.5.2. Ways of introducing a medicinal substance into the body.
9.	1.5.3. Release of a medicinal substance from a dosage form.
10.	1.5.4. Absorption of a medicinal substance in the body.
11.	1.5.5. Distribution of the drug in organs and tissues.
12.	1.5.6. Biotransformation of a medicinal substance in the body.
13.	1.5.6.1. Microsomne ​​oxidation.
14.	1.5.6.2. Non-microsomal oxidation.
15.	1.5.6.3. Conjugation reactions.
16.	1.5.7. Removal of the drug from the body.
17.	1.6. Pharmacodynamics.
18.	1.6.1. Types of action of the medicinal substance.
19.	1.6.2. Side effects of medicines.
20.	1.6.3. Molecular mechanisms of the primary pharmacological reaction.
21.	1.6.4. The dependence of the pharmacological effect on the dose of the medicinal substance.
22.	1.7. The dependence of the pharmacological effect on the dosage form.
23.	1.8. The combined effect of medicinal substances.
24.	1.9. Incompatibility of medicinal substances.
25.	1.10. Types of pharmacotherapy and the choice of a drug.
26.	1.11. Means affecting the afferent innervation.
27.	1.11.1. Absorbent agents.
28.	1.11.2. Enveloping products.
29.	1.11.3. Emollients.
30.	1.11.4. Astringents.
31.	1.11.5. Local anesthetics.
32.	1.12. Esters of benzoic acid and amino alcohols.
33.	1.12.1. Esters of yard-aminobenzoic acid.
34.	1.12.2. Substituted amides acetanilide.
35.	1.12.3. Irritant agents.
36.	1.13. Means that affect the eferent innervation (mainly on the peripheral mediator systems).
37.	1.2.1. Drugs affecting the function of cholinergic nerves. 1.2.1. Drugs affecting the function of cholinergic nerves. 1.2.1.1. Direct cholinomimetic agents.
38.	1.2.1.2. Direct-acting H-cholinomimetic agents.
39.	Olinomimetichny means of indirect action.
40.	1.2.1.4. Anticholinergics.
41.	1.2.1.4.2. H-anticholinergic drugs ganglionic drugs.
42.	1.2.2. Means affecting adrenergic innervation.
43.	1.2.2.1. Sympathomimetic agents.
44.	1.2.2.1.1. Direct acting sympathomimetic agents.
45.	1.2.2.1.2. Indirect sympathomimetic agents.
46.	1.2.2.2. Antiadrenergic drugs.
47.	1.2.2.2.1. Sympathetic means.
48.	1.2.2.2.2. Adrenergic blocking agents.
49.	1.3. Drugs affecting the function of the central nervous system.
50.	1.3.1. Drugs that inhibit the function of the central nervous system.
51.	1.3.1.2. Sleeping pills.
52.	1.3.1.2.1. Barbiturates and related compounds.
53.	1.3.1.2.2. Benzodiazepine derivatives.
54.	1.3.1.2.3. Aliphatic hypnotics.
55.	1.3.1.2.4. Nootropic drugs.
56.	1.3.1.2.5. Sleeping pills of different chemical groups.
57.	1.3.1.3. Ethanol.
58.	1.3.1.4. Anticonvulsants.
59.	1.3.1.5. Analgesic remedies.
60.	1.3.1.5.1. Narcotic analgesics.
61.	1.3.1.5.2. Non-narcotic analgesics.
62.	1.3.1.6. Psychotropic medicines.
63.	1.3.1.6.1. Neuroleptic drugs.
64.	1.3.1.6.2. Tranquilizers.
65.	1.3.1.6.3. Sedatives.
66.	1.3.2. Drugs that stimulate the function of the central nervous system.
67.	1.3.2.1. Psychotropic drugs for zbudzhuvalnoy action.
68.	2.1. Respiratory stimulants.
69.	2.2. Antitussives.
70.	2.3. Expectorants.
71.	2.4. Drugs used in cases of bronchial obstruction.
72.	2.4.1. Bronchodilators
73.	2.4.2. Protyalergic, desensitizing agents.
74.	2.5. Drugs used for pulmonary edema.
75.	3.1. Cardiotonic drugs
76.	3.1.1. Cardiac glycosides.
77.	3.1.2. Non-glucosidic (non-steroidal) cardiotonic drugs.
78.	3.2. Antihypertensive drugs.
79.	3.2.1. Neurotrophic drugs.
80.	3.2.2. Peripheral vasodilators.
81.	3.2.3. Calcium antagonists.
82.	3.2.4. Means that affect water-salt metabolism.
83.	3.2.5. Agents affecting the renin-anpotensin system
84.	3.2.6. Combined antihypertensive drugs.
85.	3.3. Hypertensive drugs.
86.	3.3.1 Agents that stimulate the vasomotor center.
87.	3.3.2. Means that tone the central nervous and cardiovascular systems.
88.	3.3.3. Means of peripheral vasoconstrictor and cardiotonic action.
89.	3.4. Lipid-lowering drugs.
90.	3.4.1. Indirect angioprotectors.
91.	3.4.2 Direct-acting angioprotectors.
92.	3.5 Antiarrhythmic drugs.
93.	3.5.1. Membranostabilizatori.
94.	3.5.2. P-blockers.
95.	3.5.3. Potassium channel blockers.
96.	3.5.4. Calcium channel blockers.
97.	3.6. Drugs used to treat patients with coronary heart disease (antianginal drugs).
98.	3.6.1. Means that reduce myocardial oxygen demand and improve its blood supply.
99.	3.6.2. Means that reduce myocardial oxygen demand.
100.	3.6.3. Means that increase the transport of oxygen to the myocardium.
101.	3.6.4. Means that increase myocardial resistance to hypoxia.
102.	3.6.5. Means that are prescribed to patients with myocardial infarction.
103.	3.7. Means that regulate blood circulation in the brain.
104.	4.1. Diuretics.
105.	4.1.1. Agents acting at the level of the cells of the renal tubules.
106.	4.1.2. Osmotic diuretics.
107.	4.1.3. Drugs that increase blood circulation to the kidneys.
108.	4.1.4. Medicinal plants.
109.	4.1.5. Principles of the combined use of diuretics.
110.	4.2. Uricosuric funds.
111.	5.1. Agents that stimulate uterine contractility.
112.	5.2. Means for stopping uterine bleeding.
113.	5.3. Means that reduce the tone and contractility of the uterus.
114.	6.1. Means that affect appetite.
115.