Medicines affecting the hematopoietic system are subdivided into those affecting the processes of erythropoiesis and leukopoiesis, i.e. drugs that affect the development of erythrocytes and leukocytes.
The cellular elements of the blood are formed in specialized hematopoietic organs, which in an adult are the red bone marrow located in the flat bones of the axial skeleton - the sternum, ribs, vertebrae. The mass of the bone marrow in an adult is about 2.0-2.5 kg.
In addition, a certain role in the hematopoiesis of lymphoid cells (lymphocytes) belongs to the lymph nodes, tonsils, appendix, spleen, where the precursors of lymphocytes get from the bone marrow and thymus gland.
The hemostasis system is represented by closely related, but independent processes: cellular (primary) hemostasis, plasma (secondary) hemostasis and fibrinolysis. In the composition of each of the systems there are factors, the action of which is aimed at maintaining the constancy of the internal environment of the body, namely: maintaining the blood in a liquid state or, if necessary, the formation of a thrombus.
Classification:
Hemostatic and antithrombotic agents
Drugs that stimulate erythropoiesis (Drugs in this group are used to treat anemia):
a) remedies for the treatment of iron deficiency (hypochromic anemias)
with iron deficiency anemia
iron preparations: Ferrous sulphate, Ferrous lactate, Ferrum Lek,
cobalt preparations: Coamid
with anemia of certain chronic diseases
Epoetin alfa (Eprex) Solution for infusion
b) drugs for the treatment of hyperchromic anemias (megaloblastic)
Cyanocobalamin Folic acid
Erythropoiesis suppressants:
Phosphorus-32-labeled sodium phosphate solution
Drugs affecting leukopoiesis:
a) drugs that stimulate leukopoiesis
Sodium nucleinate, Pentoxil, Molgramostim, Filgrastim
b) drugs that inhibit leukopoiesis
Novambikhin, Mielosan, Mercaptopurine, Dopan, Thiophosphamide
Stimulants of erythropoiesis are adrenocorticoid hormone, growth hormone, thyroid-stimulating hormone, gonadotropic hormone, glucocorticoids, catecholamines, thyroxine and triiodothyronine. All hormones have a stimulating effect on bone marrow hematopoiesis by stimulating the release of erythrocoetin, which in turn stimulates the processes of differentiation and proliferation of all megakaryocytes in the red brain.
Hematopoietic stimulants include a stimulant vitamin B12, folic acid, vitamin B2, vitamin B6, ascorbic acid, iron, manganese, cobalt, zinc, copper.
Drugs used for hypochromic (iron deficiency) anemia. Anemias are called hypochromic, in which the hemoglobin content in erythrocytes decreases. Most often, hypochromic anemias are associated with a lack of iron in the body, which is necessary for the synthesis of hemoglobin. Iron, entering the body with food, is absorbed in the small intestine. For normal absorption of iron, hydrochloric acid of gastric juice is necessary. In the body, iron is involved in the synthesis of hemoglobin, and is also part of a number of enzymes. Iron absorption is facilitated by small amounts of copper and cobalt.
Iron deficiency anemias occur with insufficient intake of iron from food (for example, in infants with artificial milk feeding), with impaired absorption of iron in the intestine (for example, with a lack of hydrochloric acid in gastric juice), with increased excretion of iron from the body (in case of bleeding) ...
Drugs affecting hematopoiesis
Lecture 16. Medicines acting on blood
Drugs affecting hematopoiesis.
* Stimulants of erythropoiesis.
* Stimulants of leukopoiesis.
Drugs affecting blood clotting.
* Anticoagulants.
* Coagulants.
Plasma replacement and detoxification solutions.
Literature:
Subbotin V.M., Subbotina S.G., Aleksandrov I.D. Modern medicines in veterinary medicine. / Series “Veterinary and animal husbandry”, Rostov-on-Don: “Phoenix”, 2000. - 592 p.
Pharmacology / V.D. Sokolov, M.I. Rabinovich, G.I. Gorshkov and others. Under. ed. V.D. Sokolov. - M.: Kolos, 1997 .-- 543 p.
I.E. Mozgov. Pharmacology. - M.: Agropromizdat, 1985 .-- 445 p.
D.K. Chervyakov, P.D. Evdokimov, A.S. Vishker. Medicines in veterinary medicine. - M.: Kolos, 1977 .-- 496 p.
M.I. Rabinovich. Workshop on Veterinary Pharmacology and Formulation. - M.: Agropromizdat, 1988 .-- 239 p.
5.M.D. Mashkovsky. Medicines. - Moscow: "New Wave", 2000 volume 1 - 530 p., Volume 2 - 608 p.
6. D.A. Kharkevich. Pharmacology. - M.: Medicine, 1999 .-- 661 p.
7. V.N. Zhulenko, O. I. Volkova, B.V. Usha and others. General and clinical veterinary formulation. - M.: Kolos, 1998 .-- 551 p.
8. I.F. Klenova, N.A. Eremenko. Veterinary drugs in Russia. Directory. - Selkhozizdat, 2000 .-- 543 p.
9. Teaching aid for independent work of students in general and private pharmacology / Tolkach NG, Arestov IG. Golubitskaya A.V., Zholnerovich Z.M. and others - Vitebsk, 2000.-37 p.
Modern pharmacological agents and methods of their application: teaching aid on private pharmacology. / Tolkach N.G., Arestov I.G., Golubitskaya A.V. and others - Vitebsk 2001 - 64 p.
Hemopoiesis in animals is carried out in the bone marrow, thymus, spleen, and liver. The main processes are erythropoiesis, leukopoiesis and thrombocytosis.
The end result of erythropoiesis is the formation of red blood cells. The main part of red blood cells is hemoglobin, which is the carrier of oxygen. Hemoglobin contains 2-valent iron. With a lack of iron, erythropoiesis is disturbed. Iron deficiency in the body occurs with blood loss, during pregnancy, in growing young animals (especially in piglets with a long suckling period, there is almost no iron in the milk of sows). In all these cases, hypochromic anemia can develop.
The basis for the development of hypochromic anemias is insufficient production of hemoglobin by the erythroblasts of the bone marrow due to iron deficiency or a violation of its metabolism.
Iron is contained in the human body in the amount of 2 - 5 g.
Its main part (2/3) is part of hemoglobin. The rest is located in tissue depots (in the bone marrow, liver, spleen). Iron is also part of myoglobin and a number of enzymes.
Only ionized iron is absorbed from the gastrointestinal tract, and best of all in the form of a bivalent ion. Hydrochloric acid (converts molecular iron into ionized form) and ascorbic acid (reduces ferric iron to bivalent) promotes the absorption of iron from the digestive tract. Absorption occurs mainly in the small intestine (especially in the duodenum 12) due to active transport and, possibly, by diffusion. The protein apoferritin contained in the intestinal mucosa binds part of the absorbed iron, forming a complex with it - ferritin. It is absorbed into the blood and in the blood serum enters into a bond with b 1 - globulin - transferrin, a ferritransferin complex is formed.
Ferritransferin enters various tissues, where it interacts with tissue apoferritin and forms ferritin again, which is deposited in the depot. In the bone marrow, iron is involved in the formation of hemoglobin. In tissue depots, iron is in a bound state (in the form of ferritin and hemosiderin).
The intensity of iron absorption largely depends on the degree of saturation of the proteins involved in its transport and deposition (apoferritin of the intestinal mucosa, blood plasma transferrin, apoferritin of tissue depots).
When erythrocytes are destroyed, part of the hemoglobin breaks down to form bilirubin and hemosiderin, which also serve as a reserve form of iron.
Topically, iron preparations, as the concentration increases, act accordingly astringent, irritating and cauterizing. Taken orally in small concentrations, iron preparations act astringently and reduce the inflammatory process, and by binding with hydrogen sulfide, a natural irritant of the mucous membrane receptors, they weaken peristalsis, act antimicrobial and anti-fermentation, and lead to the development of constipation. In addition, when iron interacts with hydrogen sulfide, insoluble iron sulfide is formed, which settles on the intestinal mucous membranes and protects them from irritation that promotes peristalsis. High doses of iron may cause vomiting, gastroenteritis, diarrhea.
For acute poisoning with iron preparations, deferroxamine is used.
Iron is excreted by the digestive tract (the non-absorbed part, with the epithelium of the mucous membrane, which undergoes desquamation, with bile), kidneys and sweat glands.
Iron preparations are used to stimulate hematopoiesis in post-hemorrhagic anemias: alimentary and chronic, arising from chronic blood loss in invasive diseases, diseases of the stomach and intestines, kidneys, bladder, hemorrhagic diathesis; with toxic anemia, leukemia, myocardosis.
Should not be administered concomitantly with tetracycline. they impair the absorption of the antibiotic.
Reduced iron
Ferrum reductum.
Fine from gray to dark gray, shiny or matte powder. Attracted by a magnet, contains at least 99% iron.
Release form - powder, coated tablets of 0.2 g.
Assign orally in pills, boluses, cereals. It is administered orally after feeding 3 times a day.
Doses for horses and cattle 1 - 5 g; donkeys 0.5 - 2 g; small ruminants 0.5 - 1 g; pigs 0.3 - 0.8 g; dogs 0.1 - 0.3 g; cats and poultry 0.01 - 0.1 g.
Iron lactate
Greenish-white crystalline powder. Poorly soluble in water.
Release form - powder.
Used as reduced iron.
Doses for horses and cattle 1 - 3 g; small ruminants and pigs 0.3 - 1 g; dogs 0.02 - 0.1 g; chickens 0.005 - 0.01 g.
Iron oxide chloride
Ferri trichloridum.
Yellow-brown crystalline mass or lumps with a faint smell of hydrogen chloride.
Let's dissolve in water.
Release form - powder and aqueous solution containing 10 - 10.3% iron (Ferri trichloridum solutum).
The antimicrobial effect is more pronounced than that of ferrous sulfate.
Applied externally to stop minor bleeding (1 - 6% solution) and as a cauterizing agent (10 - 30% solution) for arrow cancer, rapid granulation of wounds.
Ferrous ferrous sulfate, ferrous sulfate, ferrous sulfate)
Ferri (II) sulfas.
Prismatic transparent crystals of light bluish-greenish color or crystalline pale green powder.
Release form - powder.
It has a pronounced local effect depending on the concentration: 0.1% - astringent; 3.5% - irritating, and in high concentrations - cauterizing effect.
Acts antimicrobial and deodorant.
When administered orally, it irritates the mucous membranes of the stomach and intestines, increases secretion.
After absorption, it stimulates erythropoiesis, improves metabolism.
For the prevention and treatment of anemia in suckling pigs, when they reach 3 - 5 days of age, the nipples of sows before sucking are sprayed with a 0.25% solution or a solution containing 0.25% iron sulfate and 0.1% copper sulfate.
Iron ferrous carbonate with sugar
Ferri carbonas saccharatus.
Amorphous greenish-gray powder of sweet, slightly astringent taste, insoluble in water.
Release form - powder.
Doses (per animal) for horses and cattle 2 - 5 g; donkeys 1 - 3 g; small ruminants and pigs 0.5 - 1 g; dogs 0.05 - 0.2 g; cats and poultry 0.02 - 0.1 g.
Iron ascorbic acid
Acidum Ferroascorbinicum.
A complex compound of iron and ascorbic acid.
Black-violet powder with a metallic sheen.
Release form - powder and tablets of 0.5 g.
Applied with hypochromic anemia and hypovitaminosis C.
Dose inside piglets at 0.002-0.01 g / kg.
Ferkoven
Fercovenum. Transparent liquid of reddish color, sweet taste.
Solution for intravenous administration containing iron sucrose, cobalt gluconate and carbohydrate solution.
1 ml contains 0.02 g of iron and 0.00009 g (0.09 mg) of cobalt.
Release form - in ampoules and hermetically sealed 5 ml vials.
Used for hypochromic anemia.
It is administered intravenously to dogs in doses of 2-5 ml once a day, when it is required to quickly replenish the amount of iron in the body. Cobalt helps to stimulate erythropoiesis. Contraindicated in liver diseases.
Iron dextran preparations are complex compounds of iron hydroxide and low molecular weight dextran. Dextran is a bacterial polysaccharide synthesized from sucrose by bacteria. After partial depolymerization, dextran with a molecular weight of 40,000 - 80,000 is used as a plasma substitute.
After the introduction of iron dextrans into the muscles, absorption occurs mainly within 1 - 3 days, but traces of these drugs in the muscles remain for another 4 - 14 days. From the lymphatic vessels, iron dextran quickly pass into the bloodstream, from where they enter the reticuloendothelial cells, where iron is separated from dextran. Dextran is excreted mainly in the urine, but some of it can be converted to glucose.
The released iron enters the bloodstream, where it combines with transferrin and is carried throughout the body, providing a specific effect.
Ferroglyukin
Ferroglukin is a colloidal liquid of red-brown color, containing in 1 ml 50 mg (5 5% solution) or 75 mg (7.5% solution) of ferric iron.
Release form - in bottles of 10; 100 and 200 ml.
It is used for the prevention and treatment of alimentary anemia in piglets. Injected intramuscularly in the thigh area and behind the ear.
For prophylaxis, piglets at 3 - 7 days of age are injected once in doses of 1.5 - 2 ml of a 5% solution or 1 - 1.5 ml of a 7.5% solution. If necessary, after 6 to 10 days, they are re-administered in the same doses. For treatment, in a dose of 150 mg of iron per 1 kg of weight of a piglet, 15 - 20 mg - a calf and a foal; sows - 10 ml 15 - 20 days before farrowing; lambs - 3 - 4 ml for 5 - 6 days of life; calves and foals - 5 - 8 ml for 3-4 days of life.
Ferrodex
Release form - solution in ampoules of 2 and 10 ml.
Intramuscularly to piglets 2; calves, foals 5 - 10; dogs, fur animals, cats, rabbits 1 - 3 ml.
For prophylactic purposes, piglets are injected 1 time in 4 - 5 days after birth, and calves 1 - 3 times with an interval of 7 - 10 days.
Dextrofer - 100
Iron dextran complex (in 1 ml - 95 - 100 mg of ferric iron).
Applied for prophylactic and therapeutic purposes.
Release form - bottles of 100 ml.
Intramuscularly administered for prophylactic purposes to piglets for 2 - 3 days, to calves on 7 - 10 days; for therapeutic purposes (twice) with an interval of 7 days in doses (ml): for piglets - 1.5; calves 5 - 10; lambs, kids 2 - 3 ml.
Biofer
Complex preparation containing ferroglukin-75 and liquid aloe extract. Sterile red-brown liquid in 2 ml ampoules. Contains 37-38 mg of iron in 1 ml and aloe biological substance (amino acids, trace elements, etc.). Assign to piglets.
DIF-3
A mixture of iron dextran with polyvinyl alcohol and iodine. In 1 ml - 52-56 mg of iron and 5-6 mg of iodine.
The liquid is brown.
Release form - bottles of 100, 200, 400 ml.
Assign to piglets, calves, pregnant and suckling sows.
Ferro is also used - 200; Ferrumlek; Hematopan; WPPT - 3; microanemin, hemostimulin.
Drugs affecting the blood system.
- Basic terms used when parsing a topic.
- Classification of drugs affecting the blood system.
- Characteristics of drugs affecting erythropoiesis
- Characteristics of drugs affecting leukopoiesis
- Thrombus formation scheme
- Characteristics of hemostatic agents
- Characteristics of antithrombotic agents
- Characteristics of drugs affecting fibrinolysis
Basic terms used in the topic.
Anemia is an insufficient amount of red blood cells or iron in the blood.
Leukopenia is an insufficient content of leukocytes in the blood.
Hemostasis - stopping bleeding.
Thrombus formation - intravascular thrombus formation
Fibrinolysis is the phenomenon of thrombus melting, which is necessary to maintain normal blood microcirculation.
Platelet adhesion - adhesion of platelets to the damaged endothelium of the vessel.
Platelet aggregation is the accumulation of platelets in the area of vessel damage.
Consolidation - thickening of a thrombus
Erythropoiesis - the formation of red blood cells by the red bone marrow
Leukopoiesis is the formation of leukocytes by a white sprout of red bone marrow.
Classification of drugs affecting the blood system.
1. Drugs affecting erythropoiesis.
A. Stimulating erythropoiesis
· Iron preparations for oral administration: hemofer, ferrogradumet, tardiferon, Totema, sorbifer.
· Iron preparations for parenteral administration: fercoven, Ferrum lek, ferbital.
Vitamin preparations: Cyanocobalamin, folic acid, pyridoxine, riboflavin, combined preparations of vitamins.
B. Depressing erythropoiesis.
Radioactive phosphorus.
2. Drugs affecting leukopoiesis.
A. Stimulating leukopoiesis
Methyluracil, leucogen, pentoxil.
B. Oppressive leukopoiesis.
Dopan, myelosan, methotrexate, mercaptopurine.
3. Agents affecting the function of hemostasis.
A. Increasing blood clotting (hemostatics)
1.Coagulants:
Direct: thrombin, fibrin, hydrogen peroxide, hemostatic sponge, statin, calcium chloride
· Indirect: vitamin K, vicasol.
2. Antifibrinolytic (inhibitors of fibrinolysis)
Aminocaproic acid, amben, contrikal, gordox
3. Angioprotectors (drugs that reduce the permeability of the vascular wall).
Dicinone, ethamsylate, Dobezilat, ascorbic acid, rutin, Ascorutin.
4. Medicinal herbal raw materials.
Nettle leaf, water pepper herb, shepherd's purse, yarrow, bark viburnum.
B. Antithrombotic (reducing blood clotting)
1.Antiplatelet agents.
Aspirin, courantil, ticlopidine, xanthinol nicotinate, pentoxifylline.
2. Anticoagulants.
· Direct action: heparin, hirudin.
· Indirect action: warfarin, Phenilin, syncumar, neodikumarin.
· Outside the body: sodium citrate.
3.Fibrinolytic.
Direct acting: fibrinolysin
· Indirect action: streptokinase.
Erythropoiesis stimulants.
Anemia- a painful condition characterized by a general disorder of the blood and a qualitative change in its composition.
Types of anemia:
Hypochromic
· Hyperchromic.
Hypochromic anemia- Iron-deficiency anemia. The body contains 2-5 grams of iron, 70% of which is part of hemoglobin, the rest - in the bone marrow, liver, spleen.
Symptoms: pallor of the skin, weakness, dizziness, palpitations, discomfort in the region of the heart, shortness of breath to fainting.
Hypochromic anemia is characterized by a sharp decrease in hemoglobin in erythrocytes.
- Extensive blood loss
- Lack of iron in food
- Diseases of the gastrointestinal tract associated with low acidity.
Iron preparations are prescribed, which is absorbed in an acidic environment, passing from 3-valent to 2-valent, which binds to protein and is absorbed. Therefore, iron preparations are prescribed with ascorbic acid or contains ascorbic acid in the composition.
It is prescribed after meals without chewing. Solutions - through a tube. This prevents the formation of black plaque on the teeth. Darkening of feces, constipation, and dyspeptic disorders will also be a side effect.
Contraindications: fever, gastrointestinal ulcer, tuberculosis, organic heart disease. Do not combine with tetracycline antibiotics. Treatment is started with oral drugs. Parenteral administration is prescribed in case of impaired absorption by the stomach, poor tolerance, in the absence of an effect, and is prescribed in a hospital setting.
Hyperchromic anemia- this is an increase in the hemoglobin content, but the number of erythrocytes sharply decreases, and new immature forms are formed.
Drugs affecting hematopoiesis
Means that reduce rhythmic contractions and tone of the myometrium
Means that predominantly increase the tone of the myometrium
Side effects: headache, dizziness, increased blood pressure, cardiac arrhythmias.
Medicines that reduce the rhythmic contractions and tone of the myometrium are used to stop premature labor and are therefore called tocolytic means(Greek tokos - childbirth).
Β 2 -adrenomimetics are used as tocolytics - salbutamol, terbutaline, fenoterol(partusisten), ritodrin, hexoprenalin(ginipral). To stop premature labor, these drugs are administered intravenously, and when the effect is achieved, they continue to be prescribed orally. In addition, they are used for threatening abortion, to suppress uterine contractions during surgical interventions, with excessively strong labor.
The tocolytic effect is magnesium sulfate with intramuscular or intravenous administration, and ethanol.
Means that weaken the contractions of the myometrium may be useful for algodismenorrhea. To reduce pain, a myotropic antispasmodic is used drotaverine(no-shpa) and also
NSAIDs, which have not only an analgesic effect, but also weaken the contractions of the myometrium due to a violation of the synthesis of prostaglandin F 2 a. NSAIDs for algodismenorrhea are recommended ibuprofen(brufen) as one of the least toxic NSAIDs.
Chapter 22. Drugs affecting the blood system
Erythropoiesis stimulants include epoetins, cyanocobal-amine, folic acid, and iron preparations.
Epoetin alfa and epoetin beta- recombinant preparations of human erythropoietin. Used for anemia associated with bone marrow damage, chronic renal failure. Injected under the skin or intravenously.
Cyanocobalamin(vitamin B 12) is used for pernicious (malignant) anemia associated with the absence of Castle's intrinsic factor in the stomach, which promotes the absorption of cyano-cobalamin. The drug is injected under the skin, intramuscularly or intravenously.
Folic acid(vitamin B c) is effective in macrocytic (folate deficiency) anemia.
Iron preparations used to treat iron deficiency hypochromic anemias, i.e. anemias, in which the content of hemoglobin is reduced in erythrocytes. Hypochromic anemias are usually associated with insufficient absorption of iron, which is part of hemoglobin.
Ferrous gluconate, ferric chloride, ferrous sulfate, ferrous fumarate appoint inside. Side effects: constipation or diarrhea, dark stools, nausea, epigastric pain.
Iron dextran injected intramuscularly with intolerance to the enteral administration of iron preparations.
The main function of red blood cells is to carry oxygen from the lungs to organs and tissues, which is ensured by the presence of hemoglobin in them. A decrease in erythrocytes and (or) hemoglobin in the blood leads to the development of anemia, and a sharp increase in them leads to erythremia (polycythemia).
Violation of the training regimen, diet, excessive loads are prerequisites for fluctuations in erythropoiesis. Anemias in athletes can be associated with blood loss from trauma, and in athletes, with heavy menstruation.
Drugs affecting erythropoiesis stimulate the synthesis of hemoglobin and the formation of erythrocytes, increasing their number per unit volume of blood. This group of drugs is considered as anti-anemic drugs. Depending on the etiology and pathogenesis, different pharmacological agents are used to treat anemias. It is important to remember that anemias are often associated with various diseases, so the cause of the disease should be eliminated.
Anemias are divided into four main groups
Normoblastic (iron deficiency) anemia is characterized by an insufficient number of red blood cells with a low hemoglobin content. In this case, normal mature erythrocytes are produced, but the color index of the blood is low, therefore it is called hypochromic anemia.
Megaloblastic anemia differs in that the number of erythrocytes decreases, poikilocytes, immature forms that contain an increased amount of hemoglobin, are determined. The color indicator is increased, hence the name - hyperchromic anemia. With this anemia, there is a deficiency of vitamin B12 and / or folic acid.
Hypoplastic anemia is characterized by an insufficient number of normal red blood cells with a low hemoglobin content; bone marrow regeneration is impaired.
Hemolytic anemia is characterized by increased destruction of normal erythrocytes, insufficient activity of G-6 - FDG is observed.
Among the listed anemias, iron deficiency is the most common; it also ranks first in the world among other diseases. According to WHO, such anemia is observed in 700 million people, most often in those populations with an increased need for iron. Anemias make up 65% of all diseases of the hematopoietic organs, and iron deficiency anemia (IDA) - 85% of all types of anemias. Latent iron deficiency (LAD) occurs in 24% of apparently healthy young men, 30% of athletes, in 9 out of 10 pregnant women, and in the zones of radiation exposure, the frequency of anemia increases 3-4 times. These anemias are observed in 30-70% of children and adolescents, in 30-40% of women.
According to the US Academy of Sciences, there are several periods in the life of each person when the body's need for iron is especially high and its deficiency becomes the main cause of anemia.
- 1. Children aged 6 months to 4 years need a lot of iron, since their main food - milk - is low in iron, and due to growth and development, iron stores in the body are quickly depleted.
- 2. Teens need a lot of iron to meet the needs of a growing body.
- 3. The body of women of childbearing age has an increased need for iron to replenish blood loss during menstruation.
- 4. During pregnancy, the expectant mother increases the possibility of developing iron deficiency anemia. Iron is also necessary for the fetus itself to produce its own red blood cells.
Iron deficiency often occurs in many diseases, in particular acute and chronic poisoning with hemolytic poisons, after gastrectomy, in severe diseases of the gastrointestinal tract, some hereditary diseases, with blood loss.
The main role in the treatment of hypochromic anemias belongs to iron preparations.
Pharmacokinetics of iron preparations
Distribution of iron in the human body
Iron is an indispensable trace element (biometal) that plays an important role in the body, it is part of complex compounds. Distinguish between cellular and extracellular iron (Table 2.18). Its reserves in the body are 3-6 g (in men 50 mg-kg-1, in women 35 mg-kg "1 body weight). The body of an adult weighing 70 kg contains 4.5 g of iron, which is 0, 0065% of body weight.
About 70% of the total amount of iron is part of hemoglobin, the rest is in the bone marrow, spleen, muscles, and liver.
Hemoglobin (Hb) is the main component of erythrocytes, due to which the main function of blood is carried out - the transfer of oxygen. In terms of chemical structure, hemoglobin belongs to chromoproteins and contains an iron-containing prosthetic group - heme and protein (globin). For the discovery of the structure of hemoglobin, Perutz, a German by birth who emigrated to England, received the Nobel Prize in 1962. In the body of a healthy person, there is a constant balance between the formation and decay of red blood cells.
Thanks to the regulation mechanisms, under normal conditions, a stable level of red blood cells in the blood is ensured. The maximum effect on erythropoiesis is exerted by the amount of oxygen in organs and tissues. In this process, erythropoietin is of great importance, which is formed mainly in the kidneys (90%).
Iron preparations should be prescribed 1.5 hours before meals or 2 hours after meals. Iron metabolism in the body is regulated primarily by its absorption. Absorption of inorganic iron salts can occur in any part of the gastrointestinal tract, starting with the duodenum; there and in the initial part of the small intestine, its main part is absorbed. In conditions of deficiency, the zone of its absorption extends to the lower parts of the intestine. Numerous factors affect iron absorption. The absorption activity depends on the dosage form: iron preparations in liquid dosage form are better absorbed. The state of the intestinal microflora affects the absorption and pharmacological activity of iron.
For absorption, the iron ion must be reduced, i.e., go from the trivalent oxidation state to the bivalent one. Recovery begins in the stomach and continues in the small intestine. Iron ionization in the stomach is carried out under the action of hydrochloric acid at pH = 5 With a decrease in acidity, the absorption of iron from food may decrease. Reducing agents, such as ascorbic acid, succinate, SH-groups of amino acids (cysteine) and proteins present in food, convert iron oxide into ferrous, ferrous, promoting its absorption. Succinic acid, pyruvic acid, salts of copper, manganese, fructose also stimulate absorption. The absorption of iron from food of animal origin is 2-4 times higher than from plant food. In this case, the "meat factor" has a positive effect on the absorption of non-heme iron, in particular from plants. The content of iron and ascorbic acid in various products is presented in table 2.19. Iron sulfate salts and iron complexes with amino acids contribute to the maximum absorption of iron. Serine has the greatest effect on iron absorption. With pyridoxine deficiency, iron absorption is also increased despite an increase in plasma levels.
Ascorbic acid, in particular, forms a special complex with iron, which is soluble in the alkaline medium of the small intestine. It is believed that the positive effect of meat on the absorption of non-heme iron is due to the formation in the process of meat digestion of special transport systems for the absorption of iron, as well as the binding of cavity factors that slow down its absorption.
Factors that reduce iron absorption include phosphates, oxalates, tannins, phytates. The diet for latent iron deficiency and iron deficiency anemia should also include copper, manganese, zinc and cobalt. Copper is a part of cytochrome oxidase and diphenol oxidase, stimulates the synthesis of hemoglobin, the transition of reticulocytes to erythrocytes. Manganese also affects the synthesis of hemoglobin, stimulates oxidative processes in the body. Zinc promotes the formation of hemoglobin and erythrocytes, cobalt is part of cyanocobalamin, increases the absorption of iron in the intestine.
Antacids (calcium carbonate, ammonium and magnesium hydroxide) reduce the absorption of iron, possibly neutralizing the acidity of the gastric juice. Iron absorption is reduced when using iron preparations during or immediately after taking food. Iron absorption decreases with partial gastrectomy and massive bowel resections, cachexia, and infectious diseases.
The secret of the pancreas has an inhibitory effect on the absorption of iron, with chronic pancreatitis and cirrhosis of the liver, this process is significantly enhanced. Pancreatin inhibits excessive absorption of iron.
Absorption of iron depends both on the form of iron and on its absolute amount and is carried out by active transport or passive absorption. Active transport is carried out with the participation of enzyme mechanisms or carriers (Fig. 2.13). Iron, absorbed in an acidic form, is converted into iron oxide phosphate in the villi of the small intestine.
Iron pharmacokinetics
This complex combines with apoferritin in the villi of the epithelium to form ferritin. Iron absorption depends on the amount of apoferritin: if it is completely saturated and converted to ferritin, absorption stops.
Passive absorption consists of the diffusion of iron through the intestinal villi, and is also possible in combination with amino acids such as glycine and serine. This process occurs mainly when iron is supplied in doses exceeding its content in food.
After absorption, iron circulates in the blood in a bound state with (3-globulin (transferrin). Normally, the level of iron in plasma ranges from 66-146 μg-ml "" and depends on iron deficiency, which is accompanied by a decrease in its level in serum and increasing the ability to bind iron.
The daily loss of iron in humans is 35 mg, the bulk of this amount (21 mg) falls on the normal process of destruction of red blood cells. The iron released from the destroyed red blood cells is recycled again. Malignant neoplasms, infections, inflammation, and uremia decrease iron utilization.
About 30% of the total iron content in the body is in the depot. This amount is vital because iron deficiency anemia does not appear until the deposited iron is fully utilized. It is deposited in the form of ferritin and hemosiderin in the bone marrow, liver, spleen and other places where elements of the reticuloendothelial structures dominate. Both ferritin and hemosiderin can be a source of iron in heme synthesis in iron deficiency.
During the day, 0.51 g of iron is excreted from the body, it is also lost with desquamating skin elements and hair loss. Urinary iron excretion is 0.1 mg-day-1, but it increases with proteinuria and iron overload.
Treatment of iron deficiency anemia should be started only after the diagnosis has been established and the causes of the disease have been clarified.
According to the chemical structure, iron compounds are conventionally divided into two groups:
- a) simple, easily ionizing salts - ferrocenes, or organometallic chelate compounds;
- b) complex - polynuclear hydroxyl compounds - complexes.
Preparations of simple iron salts are used only orally, while chelates and polynuclear hydroxyl complexes are used intramuscularly and intravenously. In the treatment of iron deficiency anemia, it is better to use ferrous salts with good bioavailability. The preference is given to preparations with a high iron content and additives containing ascorbic, succinic, fumaric acids, amino acids, mucoprotease, etc.
Composition, release form and dose of some iron-containing drugs
Such drugs, taken internally, have certain advantages, namely:
- · A variety of dosage forms - tablets, pills, capsules, drops, elixirs, convenient for all age categories of patients;
- Rationally selected composition of the dosage form provides an opportunity to increase the bioavailability of iron;
- · The presence of vitamins, organic acids, enzymes in the preparations helps to reduce the side effects of iron and improve its absorption;
- · The oral route of administration is the natural route of iron intake into the body.
For better absorption of iron, a sufficient amount of free hydrochloric acid is necessary for dissolution and dissociation in the preparations used, i.e. for dissolving iron salts and converting them into a dissociated form, as well as for the reduction of Fe3 + ions to Fe2 +, which is better absorbed. Therefore, in case of insufficient secretory function of the stomach, iron preparations should be used together with gastric juice or diluted hydrochloric acid. The proteins of the mucous membrane of the stomach and intestines form complexes with iron, which promotes its absorption.
The agents affecting the hematopoiesis of the ferrocene group are of limited use, since, despite good absorption, they have the property of being deposited in adipose tissue, which is undesirable. Iron chelated compounds are low toxic, but they have a short half-life, and polynuclear iron hydroxyl complexes cannot be used orally, they are prescribed only intramuscularly or intravenously.
To determine the approximate course dose of iron preparations for parenteral administration, a number of formulas have been proposed. A single parenteral administration of the drug should not exceed 100 mg of elemental metal due to the impossibility of its complete assimilation.
With intravenous administration of iron preparations, the microelement begins to enter the erythrocytes only after 12-24 hours. The activity of absorption of iron when administered intramuscularly depends on the complex of iron with other components. For example, on the first day, only 50 mg of an iron complex with dextrin is absorbed, the rest - at a later time. In case of an overdose, iron begins to be deposited in the internal organs, which leads to the development of hemosiderosis.
When prescribing drugs inside, you must adhere to the required dosage regimen: at least 20-30 mg Fe2 + per day must enter the body. About 30% is in the depot - ferritin, hemosiderin. This can provide a dose of 100 mg in terms of Fe2 *. If the patient tolerates the drug well, the dose is increased. The maximum daily dose is 300-400 mg (no longer absorbed). The daily dose is divided into 3-4 doses, and if the iron is poorly tolerated - into 6-8 doses.
The first signs of a positive effect of iron preparations in the oral treatment of hypochromic anemia appear after a few days in the form of reticulocytosis. After 2-4 weeks, there is an increase in hemoglobin in the blood by 1 g-l "1 per day.
Treatment is long, sometimes 2-3, and often 4-6 months. The duration of IDA treatment with these drugs is determined by indicators of peripheral blood normalization and the content of serum iron. If the normalization of the peripheral blood composition occurs within 1-2 months (i.e., the hemoglobin content in men reaches 140-180 g-l-1, in women - 120-140 g-l "1), the treatment is continued For more than 1 month, but already in smaller doses - 60-80 mg of elemental iron per day.
With prolonged bleeding, supportive therapy of 20-40 mg of elemental iron is used daily for a week; after each 3-4 week break - again within a week.
Among the drugs for oral administration, iron lactate, iron sulfate, and reduced iron were widely used earlier. Currently, they are rarely used due to the presence of negative properties. The preference is given to ferramide, ferroceron and combined preparations containing iron sulfate.
Ferramide, a complex compound of iron with nicotinamide, is used for post-hemorrhagic anemia and IDA of any genesis (100 mg 3 times a day for 3-4 weeks).
Ferrocerone - sodium salt of orthocarboxybenzene ferrocerone, is prescribed 300 mg 2 times a day after meals with IDA of any genesis. The drug is well tolerated.
Ferrocal - tablets containing iron sulfate (200 mg), calcium fructose diphosphate (100 mg) and cerebrolecitin (200 mg). Used in the treatment of IDA, general loss of strength after infectious diseases, surgical interventions (2-6 tablets 3 times a day after meals).
Conferron - capsules containing 250 mg of ferrous sulfate and 35 mg of sodium dioxide sulfosuccinate, which has a certain surface activity and provides good absorption of iron and an increase in the therapeutic effect when receiving 1-2 capsules 3 times a day after meals.
Injectable iron preparations are used after extensive resections of the small intestine, in case of malabsorption in the intestine, when it is necessary to accelerate this process, for example, before surgery, as well as in chronic blood loss, when iron loss exceeds oral intake.
Ranferron is an active combined preparation containing iron fumarate (305 mg), folic acid (0.75 mg), vitamin B (5 μg), ascorbic acid (75 mg) and zinc sulfate (5 mg) in 1 capsule.
The drug is successfully used for all kinds of iron deficiency and folate deficiency anemias, 1 capsule 2-3 times a day or 3-4 teaspoons of the elixir a day.
Ferbitol - an aqueous solution of an iron sorbitol complex containing about 50% iron, is used for IDA of various etiologies daily, 2 ml (intramuscularly!) For 15-30 days. The drug is well tolerated, only in some cases nausea is possible. Contraindicated in hemochromatosis, liver dysfunction and acute nephritis.
Ferkoven is a combined drug for intravenous administration. Contains iron saccharate, cobalt gluconate and carbohydrate solution. The presence of cobalt promotes the activation of erythropoiesis. Injected into a vein very slowly: in the first 2 days, 2 ml, then 5 ml. After the elimination of iron deficiency in the body, treatment of hypochromic anemia is continued with drugs for oral administration. After the first injections of Fercovena, as with an overdose, hyperemia of the face and neck, a feeling of tightness in the chest, and pain in the lower back are possible. These manifestations disappear after the introduction of an analgesic and atropine sulfate (0.5 ml of a 0.1% solution) under the skin.
Ferrum-Lek is a drug for intravenous and intramuscular administration. For intramuscular injections, it contains tribasic iron in combination with maltose, for intravenous injections - iron saccharate. Intramuscularly inject 4 ml every other day, and intravenously - on the 1st day 2.5 ml (contents of 0.5 ampoules), on the 2nd - 5 ml, on the 3rd day - 10 ml, then 10 ml 2 times a week. Dilute with isotonic sodium chloride solution in a ratio of 1: 2.
The appearance after a few days of reticulocytosis indicates a positive effect of iron preparations. After 2-4 weeks, there is an increase in hemoglobin in the blood by 1 g-l "1 per day.
The duration of IDA treatment with these drugs is determined by indicators of normalization of peripheral blood and serum iron content. In Ukraine, actiferin and tarungreron are also used.
Side effects. After oral administration, nausea, vomiting, and decreased appetite may occur. This is due to the ability of iron preparations to easily dissociate with the formation of free iron ions, which can denature the proteins of the microvilli of the mucous membrane of the digestive tract with the development of irritation and inflammation. Iron can cause constipation due to the binding of hydrogen sulfide in the intestines. Diarrhea is also possible, when, when iron interacts with hydrogen sulfide, sulfuric iron is formed - a compound that irritates the intestinal wall. Sometimes there is a metallic taste in the mouth, dark staining of stool, dark border on the teeth or darkening of them due to binding with hydrogen sulfide. With prolonged use, insomia, tachycardia, and skin rashes may develop. With parenteral administration of iron preparations, pain may occur at the injection site, in the lower back, compression in the chest, allergic reactions - urticaria, fever, arthralgia, sometimes anaphylactic shock, collapse.
Ferrous iron preparations can damage membrane structures, promote the release and activation of biologically active substances, microsomal enzymes due to their prooxidant properties and the ability to initiate free radical reactions, lead to damage to organs and tissues. Therefore, to prevent such complications, substances with an antioxidant effect and stimulants of iron absorption are introduced into the composition of some drugs.
Recently, preparations have appeared that contain iron in microdialysis granules or specific matrices, which contributes to the gradual release of iron from the preparation, ensures good absorption and assimilation (for example, ferro-graduation).
In acute poisoning with iron preparations, a specific antidote is used - deferoxamine, which is produced in ampoules of 0.5 g of a dry preparation. To bind non-absorbed iron, it is used internally - 5-10 g (contents of 10-20 ampoules); for intramuscular administration, a 10% solution is used, dissolving the contents of the ampoule in 45 ml of water for injection. The drug is administered intramuscularly at the rate of 60-80 mg per 1 kg of body weight.
For the treatment of hypochromic anemias, in addition to iron-containing preparations, agents that affect hematopoiesis containing cobalt, in particular, coamide, are also used. They also stimulate hematopoiesis, promote the absorption of iron by the body, the synthesis of hemoglobin, etc.
Coamide is a complex compound of cobalt and nicotinamide, can be used with iron preparations. Easily absorbed, it is found in the bone marrow, liver, kidneys, blood plasma proteins, erythrocytes. It is excreted by the kidneys, as well as with the contents of the intestines.
Pharmacodynamics. Promotes the absorption of iron and its connection to metabolic processes. By stimulating the production of erythropoietin, it activates erythropoiesis. Increases the synthesis of amino acids, the activity of succinate dehydrogenase, cytochrome oxidase, increases the content of RNA and DNA in tissues.
1 ml of a 1% solution is injected subcutaneously once a day, you can use the powder orally, 100 mg 3 times a day.
Side effects: rarely - nausea, dizziness.
In the treatment of hypochromic anemias, a number of vitamins and heavy metals are prescribed.
Ascorbic acid (it is included in a number of iron preparations) forms complexes with iron, which are well absorbed in the intestine. Restores ferric iron to ferrous, which also promotes its absorption and prevents irritation of the intestinal mucosa.
Vitamin E activates heme synthesis, inhibits lipid peroxidation of erythrocyte cell membranes, preventing cell hemolysis and prolonging the life span.
Pyridoxine can normalize hematopoiesis in patients with sideroblastic anemia (congenital and acquired). In such patients, the synthesis of hemoglobin is disrupted and the accumulation of iron is found in the perinuclear mitochondria of erythroid cells.
Riboflavin indirectly contributes to the synthesis of globin, which also increases the formation of hemoglobin.
Copper sulfate is prescribed for its deficiency, observed in malnourished young children. Copper promotes the absorption of iron in the intestine and the incorporation of iron into hemoglobin, being an integral part of hemostimulin.
In recent decades, clinicians are increasingly encountering anemia that occurs in chronic renal failure (CRF), the use of high doses of cytostatics and in the terminal stage of malignant tumors, which does not respond to traditional methods of treatment (iron supplements, vitamin B12, folic acid). At the same time, the number of cases of this type of anemia is progressively increasing due to the dramatic increase in the incidence of diabetes mellitus, one of the complications of which is chronic renal failure, cancer and the expansion of the use of high-dose chemotherapy for their treatment. Research results indicate that this type of anemia is caused by a deficiency in the body of the cytokine erythropoietin (EPO). Thanks to the development of DNA technology, it has become possible to produce synthetic recombinant EPO preparations.
The history of the use of recombinant human erythropoietin began in 1977, when for the first time in a purified form it was isolated from human urine. In 1983, Amgen employees for the first time obtained a recombinant EPO preparation by introducing the human EPO gene into the ovarian cells of Chinese hamsters. In 1985, recombinant human EPO (epoetin) was first prescribed for a therapeutic purpose to a patient and a good therapeutic effect was obtained. Since 1987, recombinant EPO has become available in Europe for the first time. It was from this year that the use of EPO in sports began. During the period 1987-1990, there were several deaths among Dutch and Belgian cyclists, which are associated with the use of EPO. In 1988, the International Ski Federation included EPO in the list of doping agents, and in 1989, the Food and Drug Administration, the US government agency that controls the production and distribution of drugs in the country, authorizes the production of recombinant EPO. In 1990, the use of EPO was banned by the IOC. In 1993-1994 IA-AF implements the procedure of blood sampling at eight World Cup competitions, in 1997 the International Cycling Union and the International Ski Federation approve the procedure for selective blood testing before the start of the competition, setting the maximum permissible levels of hematocrit and hemoglobin. Although exceeding the established indicators is not a reason for disqualification, however, this procedure is aimed at protecting the athlete's body from the occurrence of possible complications associated with an increased hemoglobin content and an increased hematocrit. In 1998, the exposure of EPO use at the Tour de France was widely reported in the media. In 1999, research was intensified to develop a reliable method for detecting EPO for the Sydney Olympics.
Endogenously produced EPO is a glycated glycoprotein. The EPO molecule consists of 60% amino acids and 40% carbohydrates. EPO belongs to the family of cytokines, i.e. hormone-like immunomodulators that play the role of intercellular mediators in the immune response and many other physiological and pathological reactions. In the human body, EPO is formed mainly in the kidneys, mainly in peritubular interstitial fibroblasts of the cortex, partly in the liver (only 10-15% of the total production). EPO is one of the central regulators of erythrocyte formation in mammals, the primary mediator of the normal physiological response to hypoxia. The main feature of EPO is the control of proliferation and differentiation of erythroid progenitor cells in the bone marrow. The regulation of erythropoiesis is a complex mechanism in which, in addition to EPO, other growth factors are involved. So, normally it, together with interleukins 1, 3, 4 and granulocyte-macrophage colony-stimulating factor, stimulates the differentiation of progenitor cells for the erythrocyte colony-forming unit. High concentrations of erythropoietin can directly affect normoblasts and promote early release of reticulocytes into the blood.
Another important feature of EPO is the ability to prevent apoptosis of erythroid progenitor cells at late stages of development by inhibiting their phagocytosis by macrophages.
Among EPO drugs in medical practice, Epoetin (epogen, recormon) is most widely used for anemia caused by chronic renal failure, rheumatoid arthritis, malignant tumors, AIDS, and anemia in premature infants. EPO is often combined with iron preparations, otherwise its deficiency arises due to the rapid consumption of hemoglobin in newly formed erythrocytes for synthesis, and the effectiveness of EPO decreases sharply. To increase the therapeutic effect, it is recommended to prescribe it simultaneously not only with iron preparations, but also with folic acid, cyanocobalamin and pyridoxine.
Side effects: possible headache, arthralgia, hyperkalemia, bone marrow aplasia.
The effect develops after 1-2 weeks, the normalization of hematopoiesis - after 8-12 weeks. If chronic renal failure is not eliminated, the effect of EPO disappears 3 weeks after discontinuation of the drug. Patients with megaloblastic V., - deficient anemia are prescribed cyanocobalamin (vit. V.,). Such anemia is characterized by inhibition of the processes of hemoglobin synthesis and the formation of megaloblastic type erythrocytes. Despite the increase in the content of hemoglobin in each erythrocyte, the total amount in the blood decreases due to a decrease in the number of erythrocytes.
Cyanocobalamin is a ruby-red crystalline powder with a complex structure that includes a cobalt atom. In nature, it is synthesized by blue-green algae, bacteria, actinomycetes, in humans and animals it is produced by the intestinal microflora. It enters the body with animal products (liver, eggs, dairy products). The daily requirement is 2 mcg.
Pharmacokinetics. Absorption of vitamin B12 is possible only if there is gastromucoprotein in the stomach - the internal Castle factor, which is secreted by the parietal cells of the gastric mucosa. In combination with gastromucoprotein, vitamin B12 reaches the distal cecum, where it is resorbed through a highly specific receptor-transport mechanism. Cyanocobalamin enters the bloodstream in a free state and up to 93% of it combines with globulin. From the blood, it passes to the liver, where it turns into an active form - cobamamide, which is part of many enzymes. A small part of it enters various tissues and leukocytes. From the liver, it enters the intestines and is absorbed again. The absorption activity depends on the structure and function of the mucosa, which is supported by folic acid. The reserve of cyanocobalamin and its coenzyme in the liver is sufficient to satisfy the need for it for 2-3 years.
With parenteral administration of the vitamin, more than 50% of it is excreted by the kidneys and only 6-7% through the intestines, after oral administration by the kidneys, 1-2% are excreted, while most of it ends up in the feces.
Pharmacodynamics. Megaloblastic anemia is characterized by the course of hematopoiesis according to the megaloblastic type (erythroblast - hyperchromic megaloblast - megalocyte), degenerative changes in the nervous system (brain and spinal cord, peripheral nerves), changes in epithelial tissue, especially the gastrointestinal tract. Cyanocobalamin stimulates the transition of the megaloblastic type of hematopoiesis to normoblastic, reduces the processes of hemolysis of erythrocytes. The erythropoietic effect of cyano-cobalamin is due to its influence on metabolic processes. Together with folic acid, it takes part in the synthesis of purine and pyrimidine bases, as a result of which the synthesis of nucleic acids is enhanced, then the synthesis of methionine, a protein that is a donor of mobile methyl groups for the formation of choline, creatine, and nucleic acids necessary for hemopoiesis, is activated. Cyanocobalamin takes part in the metabolism of fats, in particular, in the synthesis of myelin and other lipoproteins, as well as in carbohydrate metabolism, promotes the active accumulation of ethyl compounds, has a positive effect on the function of the liver, nervous system, has an immunomodulatory effect, etc.
Indications for use: malignant megaloblastic anemia (vitamin deficiency B | 2), other forms of anemia - hypochromic (in combination with folic acid), hypoplastic, radiation sickness, trophic and inflammatory diseases of the central and peripheral nervous system (polyneuritis), resection of the small intestine, long-term intestinal infections, diseases of the stomach and intestines with malabsorption, convalescence after severe debilitating diseases.
The goal of treating megaloblastic anemia with cyanocobalamin is not only to normalize the blood picture and eliminate the clinical manifestations of the disease, but also to maximize the replenishment of the depot of this vitamin. For this, cyanocobalamin is first injected intramuscularly at 100-1000 μg daily or every other day for 1-2 weeks (saturation period), then maintenance therapy is carried out: the drug is administered in the same doses once a month throughout life. A positive result of such treatment is noted after 2--3 days in the form of reticulocytosis, complete normalization of hematopoiesis is observed at the end of 1--2 months of treatment.
Side effects: allergic reactions, hyperexcitability, tachycardia, pain in the region of the heart, lipid infiltration of the liver.
There is also folate deficiency or macrocytic anemia, which develops with an increase in the body's need for folic acid, for example, increased physical activity in sports, pregnancy. Macrocytic anemia is characterized by the appearance in the blood of large erythrocytes (macrocytes) rich in hemoglobin, but their total number is sharply reduced. Folic acid is an effective treatment for this condition.
Folic acid (vit. Sun) is found in the leaves of plants, liver, mushrooms. It was first isolated in 1941, the chemical structure was established in 1945. The molecule is pteridine, para-aminobenzoic and glutamic acids. Contains in food products in conjugated form (polyglutamate). Many tissues contain an enzyme that breaks down folic acid conjugates. The daily human requirement is 50 mcg of folic acid or 400 mcg of polyglutamate. The reserves of folic acid in the body are sufficient for vital functions for several months. Some anticonvulsants (diphenin), oral contraceptives, isoniazid, etc. provoke the occurrence of folic acid deficiency, disrupting its absorption in the gastrointestinal tract. Folic acid deficiency manifests itself as macrocytic anemia.
Pharmacokinetics. Folic acid from food is freely and completely absorbed in the proximal small intestine (about 50-200 μg-day-1) - The content in the blood after 36 hours is 92-98%. Almost 87% is contained in erythrocytes, the rest is in blood plasma. From the blood it enters the liver, where it is deposited and converted into active forms. About 50% of the drug is excreted by the kidneys, the rest by the intestines.
Pharmacodynamics. In the body, folic acid under the influence of folate reductase is converted into tetrahydrofolic acid, its active form, which takes part in the synthesis of purine bases necessary for the formation of RNA and DNA, methionine, serine, which plays an essential role in hematopoiesis. Due to its participation in nucleic acid metabolism, folic acid also stimulates leukopoiesis, has an early healing effect, and has a positive effect on hematopoiesis. It is characterized by lipotropic properties, reduces the fat content in the liver, regulates the metabolism and the content of choline in plasma and liver.
Indications for use: macrocytic anemia, anemia and leukopenia caused by chemical compounds and ionizing radiation, anemia arising from resection of the stomach, alimentary macrocytic anemia of newborns. With megaloblastic anemia, it is prescribed with cyanocobalamin. (Its isolated use in this pathology leads to an increase in pathological changes in the spinal cord.)
Very important is the prophylactic use of folic acid 1 month before the planned pregnancy and in the first trimester of pregnancy to prevent fetal anomalies, in particular, neural tube defects (spina bifida).
For prophylactic purposes, folic acid is prescribed orally at 0.02-0.05 mg daily, and for therapeutic purposes - 5 mg per day for 20-30 days. Already in the first week of treatment, an increase in the level of hemoglobin in the blood is observed, a complete correction of anemia occurs within 1--2 months.
Patients with various forms of anemia, liver diseases, atrophic gastritis are prescribed a preparation of fresh bovine liver, vitohepat.
Vitohepat is a clear yellow liquid, contains cyanocobalamin, folic acid and other biologically active substances. Injected intramuscularly, 1-2 ml per day.
Hypoplastic and hemolytic forms of anemia are difficult to treat. It is important to establish the cause and eliminate the etiological factor. From medicines used cyanocobalamin, folic acid, ascorbic acid, nicotinic acid and other vitamins - thiamine, riboflavin, pyridoxine. Blood transfusions and bone marrow transplants are also used.
For the treatment of patients with anemia, phytopreparations are widely used. Plants and their preparations are rich in a variety of biologically active substances and trace elements, they increase resistance to adverse influences, the general activity of the body and hematopoiesis.
The fruits of wild strawberry contain ascorbic and folic acids, pectins, sugars, salts of iron, cobalt, calcium, manganese, phosphorus, etc.
Black currant contains ascorbic acid, rutin, thiamine, carotene, pectins, sugars, organic acids, potassium, iron (almost 10 mg per 100 g), etc.
The named fruits are used in their natural form, syrups, compotes, etc.
Rosehip fruits contain ascorbic acid, rutin, riboflavin, phyloquinone, tocopherol, organic acids, pectins, sugars, flavone glucosides, salts of iron, manganese, magnesium, etc. They are used mainly in the form of a 1:20 infusion.
Application in the practice of sports training. In sports, where physical activity has long gone beyond the limits that are even remotely accessible to a simply physically developed person, it is simply impossible to overestimate the influence of the state of the entire blood supply system on sports results.
An increase in hemoglobin levels by 10-30% leads to such a significant increase in results and sports performance, which can act as the main reason for victory. Certainly, permitted hematopoietic stimulants (ceruloplasmin) have found the greatest application to increase the hemoglobin content, especially in cyclic sports focused on general and strength endurance. At the same time, the methods of limiting the development of sarcoplasmic and mitochondrial hypertrophy, which have recently become popular, give grounds for the use of these groups of drugs in strength sports. An increase in the number of red blood cells while maintaining the rheological properties of blood (i.e., fluidity) leads to an increase in the supply of oxygen and nutrients to tissues, as well as a pronounced stimulation of metabolic, in particular anabolic, processes in the athlete's body. This gives rise to a sharp increase in athletic performance.
Erythropoietin preparations for the treatment of anemia in athletes are administered subcutaneously, and their initial dosage is about 20 IU per 1 kg of body weight 3 times a week, or 10 IU per 1 kg of body weight daily. In case of insufficient effectiveness of the drug every 4 weeks, the dose can be increased by 20 IU per 1 kg of body weight 3 times a week (60 IU per 1 kg per week). When administered intravenously, the initial dosage is 40 IU per 1 kg of body weight 3 times a week, after 4 weeks the dose can be doubled. Regardless of the route of administration, the maximum dosage should not exceed 300 units per 1 kg of body weight per week. In the future, the maintenance dose is selected so that the hematocrit does not exceed 45%. When prescribing erythropoietin preparations, it is necessary to take into account that it is extremely important to provide the body with an adequate amount of all essential nutrients (macronutrients), as well as vitamins, minerals, especially iron, vitamin B12 and folic acid.
With the unauthorized use of EPO in sports due to a violation of the rheological properties of blood and the aggregation ability of erythrocytes and platelets, thrombus formation is activated. In professional cycling, where EPO preparations are very widely used, a hematocrit level of 50% and above serves as a basis for removing a participant from the start.
In professional sports, erythropoietin preparations are often used in combination with stanozolone, insulin and growth hormone, but it should be remembered that EPO preparations are classified as doping, so you should refrain from using them.
In addition to erythropoietin preparations, other, unauthorized drugs can be used to stimulate hematopoiesis: various preparations of iron, vitamin B12, folic acid, methyluracil, sodium nucleinate, ceruloplasmin. At the same time, the effectiveness of their use has not been studied enough.
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