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Drugs that affect the coagulation system

The homeostatic system is the body’s defense mechanism. Its task is to maintain the integrity of blood vessels and blood circulation.

The cells of the hematopoietic system are derived from common stem cells, which show the ability to differentiate into parental cells for the lymphoid or myeloid lineage. Cytokines are responsible for the differentiation of stem cells and their proliferation into individual cell lines. This group of factors that play such an important role include:

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  • Erythropoietin – produced by the kidneys in hypoxia, it is a hormone responsible for stimulating the production of red blood cells (erythrocytes) that transport oxygen from the lungs to the body’s tissues. From the kidneys of EPO, it goes to the bone marrow, where it stimulates the process of creating new erythrocytes. Increased production of the hormone occurs until the oxygen level in the blood becomes sufficient to meet the body’s needs.

  • Thrombopoietin – stimulates the proliferation and maturation of megakaryocytes. Produced mainly in the liver, spleen and marrow,

  • G-CSF – stimulates the growth and heating of neutrophils and their release into the bone marrow

  • M-CSF – stimulates the growth of macrophage colonies.

GM-CSF – stimulates the growth of granulocyte and macrophage colonies.

Deficiency of erythropoietic cell maturation factors, mainly iron, vitamin B12 and folic acid, as well as the deficit of erythropoietin and many other factors lead to ISIS. Anemia is a relatively common problem in doctor’s offices. As a result, the GP often makes preliminary and further explanations. Of particular importance is iron deficiency anemia, which often occurs in conjunction with other causes of anemia, such as anemia in chronic disease. Anemia in the elderly is also being investigated, particularly anemia caused by kidney disease. We distinguish the following types:

1. Iron deficiency anemia. The diagnosis is made on the basis of the assessment of several parameters. The basic examination is blood count. The daily iron requirement in women is about 2 mg, and in men 1 mg. In food, iron is present in the form of salts or combinations with proteins as trivalent. With this degree of oxidation, iron is difficult to absorb through the gastrointestinal mucosa. In gastric juice, under the influence of appropriate ingredients, they are reduced to divalent iron compounds. Treatment of iron deficiency consists in administering bivalent iron preparations by the oral route: Tardyferon, Sorbifer Durules, Feroplex, Ferrum Lek. They should be given between meals or on an empty stomach. The absorption of iron is facilitated by ascorbic acid and fructose.

2.Megaloblastic anemia. The main medications in this case of anemia are vitamin B12 and folic acid. The erythrocyte development disorder is caused by a deficiency of vitamin B12 and / or folic acid. Both vitamins are involved in DNA synthesis in immature bone marrow cells. Red blood cells (normocytes) do not develop, but megalocytes, which, due to the inhibition of many divisions, pass to the peripheral blood in a reduced amount.

3.Vitamin B12 deficiency anemia – this type of anemia is caused by the inability of the gastric mucosa to produce Castle’s internal factor, e.g. as a result of mucosal atrophy, gastric resection, autoimmunity against parietal cells or intestinal disease. In medicine, 2 forms of vit. B12: cyanocobalamin and hydroxocobalamin (it binds more strongly to plasma proteins and is a natural backup form).

4.Folic acid deficiency anemia – manifested by disorders of the cell division of the hematopoietic system. Folic acid deficiency gives faster symptoms of anemia! It rarely produces neurological symptoms! The treatment uses preparations administered orally and parenterally, but it should be remembered that supplementation with folic acid does not protect against neurological changes caused by vitamin B12 deficiency.

Drugs that affect the blood clotting system.

The blood clotting mechanism is an enzymatic process whose course is determined by many enzymes, cofactors and platelets. The deficiency of individual blood coagulation factors slows down or inhibits the blood clotting process and predisposes to the formation of bleeding disorders.

Drugs that inhibit blood clotting can be divided into:

  • Heparin – its physiological importance is based on preventing the formation of blood clots in the vascular bed and accelerating the breakdown of lipoproteins, reducing cell-type immunity, inhibiting the reaction of the antigen with the antibody and the complement system. In medicine, the properties of inhibiting blood clotting are mainly used. The mechanism of blood clotting inhibition consists in increasing the activity of antithrombin III in the blood and inhibiting the activity of factor Xa and, to a lesser extent, factors VIIa, IXa, XIa, XIIa, kallikrein and inhibiting platelet aggregation. Heparin is broken down in the digestive tract, therefore it is administered subcutaneously or intravenously. Heparin has been used in the prevention of blood clots in arteries and veins before and after surgical procedures, in performing replacement blood transfusions, in the acute phase of myocardial infarction, in dialysis with an artificial kidney.
  • Drugs that inhibit the activity of thrombin – endogenous antithrombin III, which is secreted in the liver and then into the blood, prevents the formation of blood clots by inhibiting the activity of factors of factor IIa, Xa, and to a lesser extent factors IXa, Xia, XIIa. The synthetically obtained medicinal products from this group include: argatroban and bivalirudin.
  • Drugs that inhibit platelet aggregation are divided into:
    a) drugs inhibiting the activity of cyclooxygenase in platelets: acetylsalicylic acid, ibuprofen
    b) drugs inhibiting platelet aggregation by ADP: ticlopidine, clopidogrel.
    c) drugs that inactivate glycoprotein IIb / IIIa receptors – abciximab is used with heparin and ASA, which prevents the formation of blood clots during coronary angioplasty.
  • Drugs that inhibit the production of platelets: anagrelide (preparations: Xagrid, Agrylin, Thromboreductin). The indication for their use is thrombocythemia secondary to bone marrow proliferative processes in order to reduce the number of platelets and prevent thrombotic changes.
  • Vitamin K antagonists – this group of compounds includes: acenocoumarol, dicoumarol, cloridione, warfarin. The mechanism of their action is associated with blocking the conversion of vitamin K to its active form, which reduces the incorporation of acid into the coagulation factors synthesized in the liver. With the use of vitamin K antagonists, the produced blood coagulation factors are incomplete and do not activate the clotting process.
  • Defibrinating drugs (ankrod, batroxobin) are purified fractions of some snake venoms containing enzymes that break down fibrinogen. They are used to reduce the amount of fibrinogen in the blood, to prevent blood clots in the blood vessels
  • Thrombolytic drugs (streptokinase, urokinase, anistreplase, alteplza, t-PA) – are used to dissolve clots that hinder the blood supply to vital tissues and organs. Indications for use: myocardial infarction, pulmonary embolism, venous thrombosis

Literature:

Janiec, Compendium of pharmacology, publisher: Wydawnictwo Lekarskie PZWL
Pharmacodynamics, Volume 2, a textbook for Students of Pharmacy
Mutschler, G. Geisslinger, H. K. Kroemer, P. Ruth, Mutschler Pharmacology and Toxicology.

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