Pancreatic hormones pharmacology. Pancreatic hormone preparations
Pancreatic hormone preparations
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 a-, b- and l-cells, which 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 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 b-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 as hyperglycemia, and with very high blood glucose numbers (more than 180 mg / l) and glucosuria (sugar in the urine). Hence the Latin name for diabetes mellitus: "Diabetеs mellitus" (diabetes mellitus).
Tissue requirements for glucose vary. In a number of fabrics
Brain, cells of the optic epithelium, 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 (DM), 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 due to 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 WHO, currently the number of patients with diabetes 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 is divided into two main types
1. Insulin-dependent diabetes mellitus (formerly called juvenile diabetes) - IDDM (DM-I) develops as a result of progressive death of b-cells, and therefore is associated with insufficient insulin secretion. This type makes its debut before the age of 30 and is associated with a multifactorial type of inheritance, since 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 - 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 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 b-cell ability to secrete compensatory 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 (endocrine genesis: goiter, acromegaly, pancreatic disease).
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, 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 principles of treatment, the following three traditional components remain the main methods of therapy 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 the 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 preparation of the parathyroid hormone parathyrin (parathyroid hormone), recently used very rarely, as there are more effective means. The 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 consists in 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 education under its influence. calcitriol (active form of calciferol in the kidneys). In the renal tubules, parathyrin increases calcium reabsorption and reduces phosphate reabsorption. In this case, in accordance with the content of phosphorus in the blood decreases, while the level of calcium increases.
Normal parathyrin levels 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 deformation of the bones, their fractures. In cases of overproduction of parathyrin, calcitonin which prevents the leaching of calcium from the bone tissue.
Indications: hypoparathyroidism, to prevent tetany due to hypocalcemia (in acute cases, calcium preparations or their combination with preparations of parathyroid hormones should be administered intravenously).
Contraindications: increased calcium in the blood, with heart disease, kidney disease, allergic diathesis.
Dihydrotachysterol (tachistin) - chemically close to ergocalciferol (vitamin D2). Increases the absorption of calcium in the intestines, at the same time - the excretion of phosphorus in the urine. Unlike ergocalciferol, there is no D-vitamin activity.
Indications: disorders of phosphorus-calcium metabolism, including hypocalcium convulsions, spasmophilia, allergic reactions, hypoparathyroidism.
Contraindications: increased calcium in the blood.
Side effect: nausea.
Pancreatic hormones.
insulin preparations
Pancreatic hormones are of great importance in the regulation of metabolic processes in the body. IN β-cells pancreatic islets synthesized insulin, which has a pronounced hypoglycemic effect, in a-cells counterinsular hormone produced glucagon , which has a hyperglycemic effect. Besides, δ-clititis the pancreas produce somatostatin .
With insufficient insulin secretion, diabetes mellitus (DM) develops - diabetes mellitus - a disease that occupies one of the dramatic pages of world medicine. According to WHO, the number of patients with diabetes worldwide in 2000 amounted to 151 million people by 2010, it is expected to increase to 221 million people, and by 2025 - 330 million people, which suggests its global epidemic. Diabetes mellitus causes the earliest of all diseases, disability, high mortality, frequent blindness, renal failure, and is also a risk factor for cardiovascular diseases. Diabetes mellitus ranks first among endocrine diseases. The United Nations has declared SD a pandemic of the 21st century.
According to the WHO classification (1999.) There are two main types of the disease - type 1 and type 2 diabetes (according to insulin-dependent and non-insulin-dependent diabetes mellitus). Moreover, an increase in the number of patients is predicted mainly due to patients with type 2 diabetes, which currently make up 85-90% of the total number of patients with diabetes. This type of diabetes mellitus is diagnosed 10 times more often than type 1 diabetes.
Diabetes mellitus is treated with diet, insulin preparations, and oral antibiotic drugs. Effective treatment of CD patients should provide approximately the same basal insulin level during the day and the prevention of hyperglycemia that occurs after eating (postprandial glycemia).
The main and only objective indicator of the effectiveness of diabetes therapy, reflecting the state of compensation of the disease, is the level of glycated hemoglobin (HbA1C or A1C). НbА1с or А1С - hemoglobin, which is covalently bound to glucose and is an indicator of the level of glycemia for the previous 2-3 months. Its level correlates well with the values \u200b\u200bof blood glucose levels and the likelihood of complications of diabetes. A decrease in the level of glycated hemoglobin by 1% is accompanied by a decrease in the risk of developing complications of diabetes by 35% (regardless of the initial level of HbA1c).
Correctly selected antihyperglycemic therapy is the basis of CD treatment.
History reference. The principles of insulin production were developed by L.V. Sobolev (in 1901), who, in an experiment on the glands of newborn calves (they do not yet have trypsin, decomposes insulin), showed that the pancreatic islets (Langerhansa) are the substrate of the internal secretion of the pancreas. In 1921 Canadian scientists FG Banting and Ch. H. Best isolated pure insulin and developed a method of industrial production. 33 years later, Sanger and his colleagues deciphered the primary structure of bovine insulin, for which they received the Nobel Prize.
The creation of insulin preparations took place in several stages:
First generation insulins - porcine and bovine (bovine) insulin;
Insulins of the second generation - monopic and monocomponent insulins (50s of the XX century)
Insulins of the third generation - semi-synthetic and genetically engineered insulin (80s of the XX century)
Obtaining insulin analogs and inhaled insulin (late XX - early XXI century).
Animal insulins differed from human insulin in amino acid composition: bovine insulin in amino acids in three positions, porcine insulin in one position (position 30 in chain B). Adverse immunological reactions were more common with bovine insulin than with porcine or human insulin. These reactions were expressed in the development of immunological resistance and insulin allergy.
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 monopic insulins obtained by gel chromatography. Later it was found that they contain small amounts of insulin-like peptides. The next step was the creation of monocomponent insulins (MK-insulins), which were obtained by additional purification using ionobmin chromatography. When using monocomponent pork insulins, the production of antibodies and the development of local reactions in patients were rare (now bovine and monopic pork insulins are not used in Ukraine).
Human insulin preparations are obtained either by a semisynthetic method using an enzymatic-chemical substitution at position B30 in pork insulin of the amino acid alanine for threonine, or biosynthetically using genetic engineering technology. Practice has shown that there is no significant clinical difference between human insulin and high quality monocomponent porcine insulin.
Work continues on improving and searching for new forms of insulin.
In terms of 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, concentration plays a dominant role glucose in blood. Penetrating into β-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 promotes the penetration of calcium ions into β-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, glucagon, secretin, electrolytes (especially Ca 2+), the autonomic nervous system (the sympathetic nervous system is inhibitory, and the parasympathetic nervous system has a stimulating effect).
Pharmacodynamics. Insulin acts on the metabolism of carbohydrates, proteins, fats, and minerals. The main thing in the action of insulin is its regulating effect on the metabolism of carbohydrates, a decrease in blood glucose. This is achieved by the fact that insulin promotes the active transport of glucose and other hexoses, as well as pentoses across the cell membranes and their utilization by the liver, muscle and adipose tissues. Insulin stimulates glycolysis, induces the synthesis of enzymes glucokinase, phosphofructokinase and pyruvate kinase, stimulates the pentose phosphate cycle by 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 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, 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 strengthening 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, its introduction into lipids. Along with the synthesis of triglycerides, insulin activates the synthesis of phospholipids in fat cells (phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and cardiolipin), and also stimulates the biosynthesis of cholesterol, which is necessary, like phospholipids and some glycoproteins, to build cell membranes.
With an insufficient amount of insulin, lipogenesis is suppressed, whether-useful is increased, lipid peroxidation in the blood and urine increases the level of ketone bodies. Due to the decreased activity of lipoprotein lipase in the blood, the concentration of β-lipoproteins increases, which are essential in the development of atherosclerosis. Insulin prevents the body from losing fluid and K + in the urine.
The essence of the molecular mechanism of action of insulin on intracellular processes is not fully disclosed. However, the first link in the action of insulin is binding to specific receptors of 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). At the same time, the kinase activity of the β-subunit of the receptor (Tyrosine kinase) is stimulated, it is autophosphorylated. A complex "insulin + receptor" is created, which, by endocytosis, penetrates into the cell, where insulin is released and the cellular mechanisms of the hormone action are triggered.
The cellular mechanisms of insulin action involve not only secondary mediators: cAMP, Ca 2+, the calcium-calmodulin complex, inositol triphosphate, diacyl-glycerol, but also fructose-2,6-diphosphate, which is called the third mediator of insulin in its effect on intracellular biochemical processes. It is the growth of 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.
A number of factors affect the number of receptors and their ability to bind. In particular, the number of receptors is reduced in cases of obesity, non-insulin dependent diabetes mellitus type 2, 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 the Golgi complex. The administration of insulin to patients with diabetes helps to reduce the level of glucose in the blood and the accumulation of glycogen in tissues, reduce glucosuria and associated polyuria, 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 oxybutyric acids - disappear from the blood and urine. Weight loss stops and excessive hunger disappears ( bulimia ). The detoxification function of the liver increases, 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 A decrease in the level of glucose in the blood after their subcutaneous administration begins in 15-30 minutes, the maximum effect is observed after 1.5-3 hours, the effect lasts 6-8 hours.
Significant advances in molecular structure, biological activity and medicinal properties have led to the modification of the human insulin formula and the development of short-acting insulin analogs.
The first analogue is lisproinsulin (humalog) 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 provided an acceleration of absorption from the subcutaneous depot. After injection, the onset of action is 5-15 minutes, reaching a peak in 30-90 minutes, duration of action 3-4 hours.
The second analogue is aspart (tradename - novo-rapid) modified by replacing one amino acid in position B-28 (proline) with aspartic acid, reduces the phenomenon of self-aggregation of cells of insulin molecules into dimmers and hexamers and accelerates its absorption.
The third analogue is glulisine (tradename epidra) is practically analogous to endogenous human insulin and biosynthetic normal human insulin with certain structural changes in the formula. Thus, in the B3 position, asparagine is replaced by lysine, and the 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 (epidra) improves glycemic control, also inhibits lipolysis and proteolysis, accelerates protein synthesis, activates insulin receptors and its substrates, fully consistent with the effect on these elements of ordinary human insulin.
2. Long-acting insulin preparations:
2.1. Average 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 on neutral Protamine Hagerorn: B-insulin, Monodar B, Farmasulin HNP ... Since insulin and protamine are included in HNP-insulin in equal, isophanic, ratios, they are also called isophanimic insulins;
2.2. Long-acting (ultralente) with onset of action after 6-8 hours, duration of action 20-30 hours. These include insulin preparations containing Zn2 + in their composition: suspension-insulin-ultralente, Farmasulin HL ... Long-acting drugs are administered only subcutaneously or intramuscularly.
3. Combined preparations containing standard mixtures of preparations 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 available in special syringe tubes.
To achieve maximum glycemic control in diabetic patients, an insulin therapy regimen is needed that fully mimics the physiological insulin profile during the day. Long-acting insulins have their disadvantages, in particular, the presence of a peak effect 5-7 hours after drug administration, leads to the development of hypoglycemia, especially at night. These disadvantages have led to the development of insulin analogs with pharmacokinetic properties for effective basic insulin therapy.
One of these drugs, created by Aventis - insulin glargine (Lantus) , which differs from human in three amino acid residues. Glargin-in Sulin is a stable insulin structure, completely soluble at pH 4.0. The drug does not dissolve in the subcutaneous tissue, which has a pH of 7.4, which leads to the formation of micro-precipitates at the injection site and its slow entry into the bloodstream. Slowing down the absorption is facilitated by the addition of a small amount of zinc (30 μg / ml). Slowly absorbed, insulin glargine does not have a peak effect and provides an almost basal insulin concentration during the day.
The development of new promising insulin preparations - inhalation insulin (creation of an insulin-air mixture for inhalation), oral insulin (spray for the oral cavity); buccal insulin (in the form of drops for the mouth).
A new method of insulin therapy is the introduction of insulin using an insulin pump, provides a more physiological method of drug administration, the absence of 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 ED corresponds to the activity of 0.04082 mg of crystalline insulin. The insulin dose for each patient is selected individually in a hospital setting, with constant monitoring of the level of HbA1c in the blood and the content of sugar in the blood and urine after administration of the drug. When calculating the daily dose of insulin, it should be borne in mind that 1 IU of insulin promotes the absorption of 4-5 g of sugar excreted in the urine. The patient is transferred to a diet that limits the amount of easily digestible carbohydrates.
Simple insulins are administered 30-45 minutes before meals. Medium-acting insulins are usually used twice (half an hour before breakfast and at 6 pm 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 is the appointment of standard mixtures of short-acting insulin and NPH-insulin 2/3 of the dose before breakfast, 1/3 before dinner. However, with this type of therapy, hyperinsulinemia takes place, which requires 5-6 meals a day, hypoglycemia may develop, and a high frequency of late complications of diabetes mellitus.
Intensive (basic bolus) insulin therapy - This is the use of medium-acting insulin twice a day (to create a basal hormone level) and additional administration of short-acting insulin before breakfast, lunch and dinner (imitation of the physiological bolus 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 level of glycemia with 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 desired effect. Simple insulin is used in diabetic coma, as well as in diabetes of any type, if it is accompanied by complications: ketoacidosis, infection, gangrene, heart disease, liver, surgery, postoperative period; to improve the nutrition of patients exhausted by a long illness; 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 long-acting drugs - coma, infectious diseases, during the surgical treatment of patients with diabetes.
Side effect painful injections, local inflammatory reactions (infiltrates), allergic reactions, the emergence of resistance to the drug, the development of lipodystrophy.
In case of an overdose of insulin, hypoglycemia. Symptoms of hypoglycemia: anxiety, general weakness, cold sweat, trembling limbs. A significant decrease in blood sugar leads to dysfunction of the brain, the development of coma, seizures and even death. Patients with diabetes should carry a few lumps of sugar with them to prevent hypoglycemia. If, after taking sugar, the symptoms of hypoglycemia do not disappear, you urgently need to intravenously inject 20-40 ml of a 40% glucose solution into a stream, 0.5 ml of a 0.1% adrenaline solution can be injected subcutaneously. 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 long-acting drugs explains the frequent cases of allergic reactions. However, injections of long-acting insulin preparations are less painful due to the higher pH of these drugs.
Hormone is a chemical substance that is a biologically active substance, produced by the endocrine glands, enters the bloodstream, and affects tissues and organs. Today, scientists have been able to decipher the structure of the bulk of hormonal substances, have learned how to synthesize them.
Without pancreatic hormones, the processes of dissimilation and assimilation are impossible, the synthesis of these substances is carried out by the endocrine parts of the organ. When the gland malfunctions, a person suffers from many unpleasant diseases.
The pancreatic gland is a key organ of the digestive system, it performs endocrine and excretory functions. It produces hormones and enzymes, without which it is impossible to maintain biochemical balance in the body.
The pancreas consists of two types of tissues, the secretory part, connected to the duodenum, is responsible for the secretion of pancreatic enzymes. The most important enzymes are lipase, amylase, trypsin and chymotrypsin. If there is a deficiency, enzyme preparations of the pancreas are prescribed, the use depends on the severity of the disorder.
The production of hormones is provided by islet cells, the incretor part occupies no more than 3% of the total mass of the organ. The islets of Langerhans produce substances that regulate metabolic processes:
- lipid;
- carbohydrate;
- proteinaceous.
Endocrine disorders in the pancreas cause the development of a number of dangerous diseases, with hypofunction diagnose diabetes mellitus, glucosuria, polyuria, with hyperfunction, a person suffers from hypoglycemia, obesity of varying severity. Hormone problems also arise if a woman has been taking contraception for a long time.
Pancreatic hormones
Scientists have identified the following hormones secreted by the pancreas: insulin, pancreatic polypeptide, glucagon, gastrin, kallikrein, lipocaine, amylin, vagotinin. All of them are produced by islet cells and are necessary for the regulation of metabolism.
The main pancreatic hormone is insulin, it is synthesized from the proinsulin precursor, its structure includes about 51 amino acids.
The normal concentration of substances in the human body over 18 years old is from 3 to 25 μU / ml of blood. In acute insulin deficiency, diabetes mellitus develops.
Thanks to insulin, the transformation of glucose into glycogen is triggered, the biosynthesis of hormones in the digestive tract is kept under control, the formation of triglycerides, higher fatty acids, begins.
In addition, insulin reduces the level of harmful cholesterol in the bloodstream, becoming a prophylactic agent against vascular atherosclerosis. Transportation to the cages is additionally improved:
- amino acids;
- macronutrients;
- microelements.
Insulin promotes protein biosynthesis on ribosomes, inhibits the conversion of sugar from non-carbohydrate substances, lowers the concentration of ketone bodies in human blood and urine, and reduces the permeability of cell membranes for glucose.
Insulin hormone is able to significantly enhance the transformation of carbohydrates into fats with subsequent deposition, is responsible for the stimulation of ribonucleic (RNA) and deoxyribonucleic (DNA) acids, increases the supply of glycogen accumulated in the liver, muscle tissue. Glucose becomes a key regulator of insulin synthesis, but at the same time the substance does not affect the secretion of the hormone in any way.
The production of pancreatic hormones is controlled by compounds:
- norepinephrine;
- somatostatin;
- adrenalin;
- corticotropin;
- somatotropin;
- glucocorticoids.
Provided early diagnosis of metabolic disorders and diabetes mellitus, adequate therapy can alleviate a person's condition.
With excessive insulin secretion, men are at risk of impotence, patients of any gender have vision problems, asthma, bronchitis, hypertension, premature baldness, the likelihood of myocardial infarction, atherosclerosis, acne and dandruff increases.
If too much insulin is produced, the pancreas itself suffers and becomes overgrown with fat.
Insulin, glucagon
Sugar level
To bring the metabolic processes in the body back to normal, it is required to take preparations of pancreatic hormones. They should be used strictly as directed by the endocrinologist.
Classification of pancreatic hormone preparations: short-acting, medium-duration, long-acting. The doctor may prescribe a certain type of insulin or recommend a combination of them.
The indication for short-acting insulin is diabetes mellitus and excessive amounts of sugar in the bloodstream when sweetener tablets do not help. These funds include funds Insuman, Rapid, Insuman-Rap, Aktrapid, Homo-Rap-40, Humulin.
Also, the doctor will offer the patient insulins of medium duration: Mini Lente-MK, Homofan, Semilong-MK, Semilente-MS. There are also long-acting pharmacological agents: Super Lente-MK, Ultralente, Ultrahard-NM. Insulin therapy, as a rule, is lifelong.
Glucagon
This hormone is included in the list of substances of a polypeptide nature, it contains about 29 different amino acids; in the body of a healthy person, the level of glucagon ranges from 25 to 125 pg / ml of blood. It is considered a physiological insulin antagonist.
Hormonal preparations of the pancreas, which contain an animal or, stabilize the indicators of monosaccharides in the blood. Glucagon:
- secreted by the pancreas;
- has a positive effect on the body as a whole;
- increases the release of catecholamines by the adrenal glands.
Glucagon is able to increase blood circulation in the kidneys, activate metabolism, keep under control the conversion of non-carbohydrate foods into sugar, increase glycemic parameters due to the breakdown of glycogen by the liver.
The substance stimulates gluconeogenesis, in large quantities has an effect on the concentration of electrolytes, has an antispasmodic effect, lowers calcium and phosphorus, and starts the process of fat breakdown.
For the biosynthesis of glucagon, the intervention of insulin, secretin, pancreozymin, gastrin and growth hormone is required. For glucagon to be released, there must be a normal supply of proteins, fats, peptides, carbohydrates and amino acids.
Somatostatin, vaso-intensive peptide, pancreatic polypeptide
Somatostatin
Somatostatin is a unique substance, it is produced by the delta cells of the pancreas and the hypothalamus.
The hormone is necessary for inhibiting the biological synthesis of pancreatic enzymes, lowering the level of glucagon, inhibiting the activity of hormonal compounds and the hormone serotonin.
Without somatostatin, it is impossible to adequately absorb monosaccharides from the small intestine into the bloodstream, to reduce the secretion of gastrin, inhibition of blood flow in the abdominal cavity, and peristalsis of the digestive tract.
Vaso-intensive peptide
This neuropeptide hormone is secreted by cells of various organs: the back and the brain, the small intestine, and the pancreas. The level of the substance in the bloodstream is quite low, almost does not change after eating. The main functions of the hormone include:
- activation of blood circulation in the intestine;
- inhibition of the release of hydrochloric acid;
- acceleration of excretion of bile;
- inhibition of water absorption by the intestines.
In addition, there is a stimulation of somatostatin, glucagon and insulin, the start of the production of pepsinogen in the cells of the stomach. In the presence of an inflammatory process in the pancreas, a violation of the production of neuropeptide hormone begins.
Another substance produced by the gland is a pancreatic polypeptide, but its effect on the body has not yet been fully studied. The physiological concentration in the bloodstream of a healthy person can vary from 60 to 80 pg / ml, excessive production indicates the development of neoplasms in the endocrine part of the organ.
Amilin, lipocaine, kallikrein, vagotonin, gastrin, centroptein
The hormone amylin helps to optimize the amount of monosaccharides; it prevents an increased amount of glucose from entering the bloodstream. The role of the substance is manifested by suppression of appetite (anorexic effect), arresting the production of glucagon, stimulating the formation of somatostatin, and weight loss.
Lipocaine takes part in the activation of phospholipids, oxidation of fatty acids, enhances the effect of lipotropic compounds, and becomes a measure of prevention of fatty degeneration of the liver.
The hormone kallikrein is produced by the pancreas, but it is in an inactive state in it, it starts working only after it enters the duodenum. It lowers glycemic levels, lowers blood pressure. To stimulate the hydrolysis of glycogen in the liver and muscle tissue, the hormone vagotonin is produced.
Gastrin is secreted by the cells of the gland, the gastric mucosa, the hormone-like compound increases acidity, triggers the formation of the proteolytic enzyme pepsin, and normalizes the digestive process. It also activates the production of intestinal peptides, including secretin, somatostatin, cholecystokinin. They are important for the intestinal phase of digestion.
Substance centroptein protein nature:
- stimulates the respiratory center;
- expands the lumen in the bronchi;
- improves the interaction of oxygen with hemoglobin;
- copes well with hypoxia.
For this reason, centroptein deficiency is often associated with pancreatitis and erectile dysfunction in men. Every year more and more new preparations of pancreatic hormones appear on the market, their presentation is carried out, which makes it easier to solve such violations, and they have fewer and fewer contraindications.
Pancreatic hormones play a key role in regulating the vital activity of the body, so you need to have an idea of \u200b\u200bthe structure of the organ, take care of your health, and listen to your well-being.
The treatment of pancreatitis is described in the video in this article.
The pancreas functions as a gland of external and internal secretion. The endocrine function is performed by the islet apparatus. The Langergans islets are composed of 4 types of cells:
A (a) cells that produce glucagon;
B ((3) cells that produce insulin and amylin;
D (5) cells that produce somatostatin;
F - cells that produce pancreatic polypeptide.
The functions of the pancreatic polypeptide are poorly understood. Somatostatin, produced in peripheral tissues (as noted above), acts as a paracrine secretion inhibitor. Glucagon and insulin are hormones that regulate the level of glucose in the blood plasma in a mutually opposite way (insulin lowers, and glucagon increases). Insufficiency of the endocrine function of the pancreas is manifested by symptoms of insulin deficiency (in connection with which it is considered to be the main hormone of the pancreas).
Insulin is a polypeptide consisting of two chains - A and B, connected by two disulfide bridges. Chain A consists of 21 amino acid residues, chain B - of 30. Insulin is synthesized in the Golgi apparatus (3-cells in the form of preproinsulin and converted into proinsulin, which is two insulin chains, and the C-protein chain connecting them, consisting of 35 amino acid residues After the cleavage of the C-protein and the addition of 4 amino acid residues, insulin molecules are formed, which are packed into granules and undergo exocytosis.Incretion of insulin has a pulsating character with a period of 15-30 minutes. During the day, 5 mg of insulin is released into the systemic circulation, and in total, the pancreas contains (including preproinsulin and proinsulin) 8 mg of insulin. The secretion of insulin is regulated by neuronal and humoral factors. The parasympathetic nervous system (through the M3-cholinergic receptors) enhances, and the sympathetic nervous system (through the a2-adrenergic receptors) inhibits the release insulin (3-cells. Somatostatin produced by D-cells inhibits, and some Some amino acids (phenylalanine), fatty acids, glucagon, amylin and glucose increase the release of insulin. In this case, the level of glucose in the blood plasma is a determining factor in the regulation of insulin secretion. Glucose penetrates into the (3-cell and starts a chain of metabolic reactions, as a result of which the concentration of ATP in 3-cells increases. This substance blocks ATP-dependent potassium channels and the membrane (3-cells enter a state of depolarization. As a result of depolarization, the opening frequency increases voltage-gated calcium channels The concentration of calcium ions in P-cells increases, which leads to an increase in insulin exocytosis.
Insulin regulates the metabolism of carbohydrates, fats, proteins, and tissue growth. The mechanism of influence of insulin on tissue growth is the same as that of insulin-like growth factors (see somatotropic hormone). The effect of insulin on metabolism in general can be characterized as anabolic (the synthesis of protein, fats, glycogen increases), while the effect of insulin on carbohydrate metabolism is of prime importance.
It is extremely important to note that those indicated in table. 31.1 changes in tissue metabolism are accompanied by a decrease in plasma glucose levels (hypoglycemia). One of the causes of hypoglycemia is an increase in glucose uptake by tissues. The movement of glucose through the histohematogenous barriers is carried out through facilitated diffusion (non-volatile transport along an electrochemical gradient through special transport systems). The glucose diffusion facilitated systems are called GLUT. Indicated in table. 31.1 Adipocytes and striated muscle fibers contain GLUT 4, through which glucose enters "insulin-dependent" tissues.
Table 31.1. The effect of insulin on metabolism
The influence of insulin on metabolism is carried out with the participation of specific membrane insulin receptors. They consist of two a- and two p-subunits, while the a-subunits are located on the outside of the membranes of insulin-dependent tissues and have binding sites for insulin molecules, and the p-subunits represent a transmembrane domain with tyrosine kinase activity and a tendency to mutual phosphorylation. When the insulin molecule binds to the a-subunits of the receptor, endocytosis occurs, and the insulin receptor dimer is immersed in the cytoplasm of the cell. While the insulin molecule is bound to the receptor, the receptor is in an activated state and stimulates phosphorylation processes. After separation of the dimer, the receptor returns to the membrane, and the insulin molecule is degraded in the lysosomes. Phosphorylation processes triggered by activated insulin receptors lead to the activation of certain enzymes
carbohydrate metabolism and increased GLUT synthesis. This can be schematically represented as follows (Fig. 31.1):
With insufficient production of endogenous insulin, diabetes mellitus occurs. Its main symptoms are hyperglycemia, glucosuria, polyuria, polydipsia, ketoacidosis, angiopathies, etc.
Insulin deficiency can be absolute (an autoimmune process leading to the death of the islet apparatus) and relative (in the elderly and obese people). In this regard, it is customary to distinguish between type 1 diabetes mellitus (absolute insulin deficiency) and type 2 diabetes mellitus (relative insulin deficiency). For both forms of diabetes, diet is indicated. The procedure for prescribing pharmacological drugs for different forms of diabetes is not the same.
Antidiabetic drugs
Used for type 1 diabetes
- Insulin preparations (replacement therapy)
- Synthetic antidiabetic agents
- Insulin preparations Insulin preparations
Insulin preparations can be produced from the pancreas of slaughter cattle - this is bovine (bovine) and pork insulin. In addition, there is a genetically engineered method for producing human insulin. Insulin preparations obtained from the pancreas of slaughter cattle may contain impurities of proinsulin, C-protein, glucagon, somatostatin. Modern technologies for
allow to obtain highly purified (monocomponent), crystallized and monopikovy (chromatographically purified with isolation of insulin "peak") preparations.
The activity of insulin preparations is determined biologically and is expressed in units of action. Insulin is used only parenterally (subcutaneously, intramuscularly and intravenously), since, being a peptide, it is destroyed in the gastrointestinal tract. Undergoing proteolysis in the systemic circulation, insulin has a short duration of action, in connection with which long-acting insulin preparations were created. They are obtained by the method of precipitation of insulin with protamine (sometimes in the presence of Zn ions, to stabilize the spatial structure of insulin molecules). The result is either an amorphous solid or relatively poorly soluble crystals. When injected subcutaneously, such forms provide a depot effect by slowly releasing insulin into the systemic circulation. From a physico-chemical point of view, prolonged forms of insulin are suspensions, which serves as an obstacle to their intravenous administration. One of the disadvantages of prolonged forms of insulin is a long latency period, therefore, they are sometimes combined with non-prolonged insulin preparations. This combination ensures the rapid development of the effect and its sufficient duration.
Insulin preparations are classified according to the duration of action (the main parameter):
- Fast-acting insulin (onset of action is usually 30 minutes; maximum action after 1.5-2 hours, total duration of action 4-6 hours).
- Long-acting insulin (onset after 4-8 hours, peak after 8-18 hours, total duration 20-30 hours).
- Medium-acting insulin (onset 1.5-2 hours, peak after
- 12 hours, total duration 8-12 hours).
- Medium-acting insulin in combinations.
Side effects. Currently, either genetically engineered human insulins or highly purified pig insulins are used in medical practice. Therefore, complications of insulin therapy are relatively rare. Allergic reactions, lipodystrophy at the injection site are possible. With the introduction of too high doses of insulin or insufficient intake of alimentary carbohydrates, excessive hypoglycemia may develop. Its extreme variant is hypoglycemic coma with loss of consciousness, convulsions and symptoms of cardiovascular failure. In hypoglycemic coma, the patient should be injected intravenously with a 40% glucose solution in an amount of 20-40 (but not more than 100) ml.
Since insulin preparations are used for life, it should be borne in mind that their hypoglycemic effect may be altered by other drugs. Enhance the hypoglycemic effect of insulin: α-blockers, β-blockers, tetracyclines, salicylates, disopyramide, anabolic steroids, sulfonamides. Weaken the hypoglycemic effect of insulin: p-adrenomimetics, sympathomimetics, glucocorticosteroids, thiazide diuretics.
Contraindications: diseases occurring with hypoglycemia, acute liver and pancreas diseases, decompensated heart defects.
Genetically engineered human insulin preparations
Actrapid NM is a solution of biosynthetic human insulin of short and fast action in 10 ml vials (1 ml of solution contains 40 or 100 IU of insulin). It can be produced in cartridges (Actrapid NM Penfill) for use in the Novo-Pen insulin pen. Each cartridge contains 1.5 or 3 ml of solution. The hypoglycemic effect develops after 30 minutes, reaches a maximum after 1-3 hours and lasts 8 hours.
Isophane-insulin NM is a neutral suspension of genetically engineered insulin of medium duration. 10 ml vials of suspension (40 IU in 1 ml). The hypoglycemic effect begins after 1-2 hours, reaches a maximum after 6-12 hours, and lasts 18-24 hours.
Monotard NM is a compound suspension of human zinc-insulin (contains 30% amorphous and 70% crystalline zinc-insulin. Vials of 10 ml suspension (40 or 100 IU in 1 ml). Hypoglycemic action begins after
- hours, reaches a maximum after 7-15 hours, lasts 24 hours.
Porcine insulin preparations
Insulin neutral for injection (InsulinS, ActrapidMS) is a neutral solution of monopic or monocomponent porcine insulin of short and rapid action. Vials of 5 and 10 ml (1 ml of solution contains 40 or 100 IU of insulin). The hypoglycemic effect begins 20-30 minutes after subcutaneous administration, reaches a maximum after 1-3 hours and lasts 6-8 hours. For systematic treatment, it is administered under the skin, 15 minutes before meals, the initial dose is from 8 to 24 IU (U) , the highest single dose is 40 UNITS. For relief of diabetic coma, it is administered intravenously.
Insulin isophane is a mono-peak monocomponent porcine isophane protamine insulin. The hypoglycemic effect begins in 1-3 hours, reaches a maximum after 3-18 hours, lasts about 24 hours. It is most often used as a component of combined drugs with short-acting insulin.
Insulin Lente SPP is a neutral compound suspension of monopic or monocomponent porcine insulin (contains 30% amorphous and 70% crystalline zinc insulin). 10 ml vials of suspension (40 IU in 1 ml). The hypoglycemic effect begins 1-3 hours after subcutaneous administration, reaches a maximum after 7-15 hours, lasts 24 hours.
Monotard MS is a neutral compound suspension of monopic or monocomponent porcine insulin (contains 30% amorphous and 70% crystalline zinc insulin). 10 ml vials of suspension (40 or 100 IU in 1 ml). The hypoglycemic effect begins after 2.5 hours, reaches a maximum after 7-15 hours, and lasts 24 hours.
Book: Lecture notes Pharmacology
10.4. Pancreatic hormone preparations, insulin preparations.
Pancreatic hormones are of great importance in the regulation of metabolic processes in the body. In the cells of the pancreatic islets, insulin is synthesized, which has a hypoglycemic effect, and the counterinsular hormone glucagon is produced in a-cells, 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, decomposes 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. After 33 years, 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 promotes 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 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 m-RNA 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." 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 growth of 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, to 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-semilent, 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 per 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.
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 management, 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 assimilation of glucose in diseases of the heart, liver, surgery, in the postoperative period (5 units each); to improve the nutrition of patients exhausted by a long 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, liver cirrhosis, 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 fairly 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. Routes of drug administration into the body. |
| 9. | 1.5.3. Release of a medicinal substance from a dosage form. |
| 10. | 1.5.4. Absorption of a drug 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 \u200b\u200boxidation. |
| 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 drug substance. |
| 22. | 1.7. The dependence of the pharmacological effect on the dosage form. |
| 23. | 1.8. The combined action 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. Yard-aminobenzoic acid esters. |
| 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. | Olinomimetic 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. Respiration 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 affecting 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 Means 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. |