When bleeding, hemostatic agents are used. They are divided into the following groups.

• 1. Aggregants - agents that stimulate adhesion and aggregation of platelets.
• 2. Coagulants (hemostatics) - means that stimulate thrombus formation:
  • a) direct action - thrombin;
  • b) indirect action - menadione sodium bisulfite"Vikasol" (vitamin K).
• 3. Antifibrinolytics (fibrinolysis inhibitors) - agents that reduce the activity of the fibrinolytic system.

Consider the representatives of these groups.

Aggregates. Calcium is a vital mineral necessary to maintain the balance of electrolytes in the body, the adequate functioning of numerous regulatory mechanisms, is directly involved in platelet aggregation and adhesion, but in addition, it activates thrombin and fibrin. Thus, it stimulates the formation of both platelet and fibrin clots. Basically, calcium preparations are used for bleeding associated with a decrease in its level in the blood plasma. Used as drugs calcium chloride(intravenously or orally) and calcium gluconate(intravenously, intramuscularly or orally). Rapid intravenous administration of calcium chloride can lead to cardiac arrest and lower blood pressure.

Etamzilat("Dicynone") inhibits the synthesis of prostacyclin and thus reduces its effect on platelet aggregation. It contributes to the compaction of the basement membrane of capillaries, increasing the polymerization of hyaluronic acid in it and the normalization of cerebral blood flow. With intravenous administration, the hemostatic effect develops after 5-15 minutes.

Serotonin isolated in 1947, found in various tissues, including blood (platelets). From platelets, serotonin is released when they are destroyed and takes part in the process of blood clotting. In diseases accompanied by thrombocytopenia, the amount of serotonin in the blood drops sharply (Werlhof's disease, purpura, leukemia, etc.). The hemostatic effect of serotonin is also associated with a peripheral vasoconstrictor effect. With severe bleeding, they begin with intravenous administration, with a decrease in bleeding, they switch to intramuscular injections.

coagulants. Direct-acting coagulants are preparations from the blood plasma of dopor, preparations for topical application ( thrombin, "Hemostatic sponge").

Thrombin - a natural component of the hemocoagulation system, it is formed in the body from prothrombin during its enzymatic activation by thromboplastin. Thrombin solution is used only locally to stop bleeding from small vessels, parenchymal organs (for example, during operations on the liver, brain, kidneys). Thrombin solution is impregnated with gauze swabs and applied to the bleeding surface. The introduction of thrombin solutions parenterally is not allowed, because they cause the formation of blood clots in the vessels. "Hemostatic sponge" contains boric acid, nitrofural and collagen, has a hemostatic and antiseptic effect, stimulates tissue regeneration. It is contraindicated in bleeding large vessels, hypersensitivity to furacilin and other nitrofurans.

Indirect coagulant menadione sodium bisulfite("Vikasol") is a synthetic analogue of vitamin K. Only two vitamins of the K group have been isolated from natural substances: vitamin K from alfalfa, and K2 from rotting fishmeal. In addition to natural vitamins K, a number of naphthoquinone derivatives are now known to have an antihemorrhagic effect, which were obtained synthetically. In 1943, K. Dam and E. A. Doisy received the Nobel Prize for the discovery and establishment of the chemical structure of vitamin K. ) enter the body with plant foods (spinach leaves, cauliflower, rose hips, needles, green tomatoes), are found in animal products and are synthesized by the intestinal flora. Indications for use: "Vikasol" is used for all diseases accompanied by a decrease in the content of prothrombin in the blood (hypoprothrombinemia) and bleeding. This is primarily jaundice and acute hepatitis, peptic ulcer of the stomach and duodenum, radiation sickness, septic diseases with hemorrhagic manifestations. "Vikasol" is also effective for parenchymal bleeding, bleeding after injury or surgery, hemorrhoidal, prolonged nosebleeds, etc. It is also used prophylactically before surgery, with long-term treatment with sulfa drugs and antibiotics that depress the intestinal flora, which synthesizes vitamin K. Also it is used for bleeding caused by an overdose of indirect anticoagulants. The effect develops slowly - 12-18 hours after administration.

"Vikasol" can accumulate, so its daily dose should not exceed 1-2 tablets or 2 ml of a 1% solution intramuscularly for no more than 3-4 days. If necessary, repeated injections of the drug are possible after a 4-day break and a test for the rate of blood clotting. Vikasol is contraindicated in patients with increased hemocoagulation and thromboembolism.

Herbal preparations used as a source of vitamin K also contain other vitamins, bioflavonoids, various substances that can promote blood clotting, reduce the permeability of the vascular wall. This is first of all nettle leaves, viburnum fruits, water pepper herb, arnica. From these plants, infusions, tinctures, extracts are prepared, which are used orally. Some of these drugs are used topically, moistened with gauze pads and applied for 2-5 minutes to the bleeding surface.

fibrinolysis inhibitors. Aminocaproic acid - lysine derivative. Fibrinogen and fibrin molecules contain lysine, it is with it that the active centers of plasminogen plasmin interact, then subjecting these proteins to hydrolysis. Aminocaproic acid interacts with these sites of plasminogen and plasmin, eliminates their activity, preserving the fibrin molecule and the thrombus consisting of it.

Aprotinin("Kontrykal") is an antienzymatic drug obtained from the lungs of cattle. It forms inactive complexes with plasminogen.

Aminocaproic acid and aprotinin are prescribed for bleeding associated with increased activity of the fibrinolytic system and fibrinogen deficiency, for example, with cirrhosis of the liver, portal hypertension, with bleeding after operations on organs rich in tissue plasminogen activator, when using heart-lung machines, with an overdose of fibrinolytic agents, with massive transfusions of canned blood (the possibility of developing secondary hypofibrinogenemia), and so on.

In addition, these drugs, by inhibiting proteolytic enzymes, directly (aprotinin) or indirectly, through the fibrinolysis system (aminocaproic acid), inhibit the activity of kinins. Therefore, they are used for traumatic shock, pancreatitis, burns, concussion, meningitis, i.e. in pathological conditions characterized by an increase in the activity of kinins.

Enter aminocaproic acid through the mouth, intramuscularly and intravenously; aprotinin - only intravenously.

Antihemostatics. Antihemostatics reduce the level of blood clotting. In the bloodstream, a slow process of blood clotting and dissolution of the formed clots is constantly taking place. The scheme of sequential activation of blood coagulation factors is shown in fig. 5.10.

Normally, this does not lead to impaired blood flow. Fibrinous clots in the bloodstream occur when the function of the anticoagulant system of the blood is impaired. The formation of fibrinous clots causes the occurrence of blood clots and embolism.

Rice. 5.10.

In the process of treating thrombosis and embolism, the ability to melt the clot formed in the bloodstream by the timely use of the fibrinolysin enzyme, but always in combination with heparin, becomes of great importance.

To suppress blood coagulation in the vessel, agents that reduce blood clotting are used: antiplatelet agents, anticoagulants, fibrinolytics.

Antiplatelet agents. They are classified as follows:

• cyclooxygenase inhibitors: acetylsalicylic acid("Aspirin cardio", "Buferin", "Novandol", "Trombo ACC");
• modulators of the system "adenylate cyclase - CAMP": dipyridamole;
• GP glycoprotein receptor blockers: abciximab("Reopro");
• eptifibatide("Integrilin");
• purine receptor blockers: ticlopidine, clopidogrel.

Antiplatelet agent acetylsalicylic acid at a dose of 150-300 mg (according to European recommendations) is indicated in case of acute coronary syndrome (myocardial infarction or primary unstable angina). For these purposes, the enteric form is not suitable, since the onset of its action is slow. Further, acetylsalicylic acid is used for life at a dose of 75-162 mg / day. In the presence of contraindications to acetylsalicylic acid, apply clopidogrel in a loading first dose of 300 mg and subsequently 75 mg / day. The combination of clopidogrel with aspirin is more effective than aspirin alone. Eptifibatide("Integrilin") is a synthetic heptapeptide, an inhibitor of platelet aggregation, belonging to the class of arginine-glycine-aspartate mimetics. The indication for use is the early prevention of myocardial infarction.

Anticoagulants(Means that disrupt the formation of blood clots). Direct anticoagulants - heparin and his drugs hirudin, sodium hydrocitrate, concentrate antithrombin III.

Anticoagulants of indirect action - derivatives of oxycoumarin: warfarin, acenocoumarol("Sinkumar"); indandione derivatives - phenylin. New anticoagulants xabana and gatrans - dabigatran etexilate("Pradaksa"), rivaroxaban("Xarelto"). Direct-acting anticoagulants are injectable drugs used in the initial stages of treatment and prevention of thrombosis in a short course. Indirect anticoagulants (inhibit the synthesis of coagulation factors in the liver) act slowly and are used orally.

Direct acting anticoagulants. Heparin belongs to the group of medium molecular weight heparins, the ability to inhibit thrombin and factor X is especially important. Activated factor X combines with factor V and platelet and tissue phospholipids, forming a complex called prothrombin activator. This complex, in turn, initiates the cleavage of prothrombin to form thrombin within seconds, setting in motion the final phase of the clotting process. Heparin is used for thrombosis, thromboembolism, to inhibit blood coagulation in extracorporeal circulation. Heparin ointment and other topical heparin preparations prevent the formation of blood clots in thrombophlebitis of superficial veins, and are used for tendon and joint injuries, soft tissue bruises. Rectal suppositories are prescribed for hemorrhoids. A side effect of heparin is thrombocytopenia. Heparin antagonist is protamine sulfate. 1 mg of protamine sulfate neutralizes 80-120 IU of heparin in the blood. Complexation is due to the binding of cationic groups (due to arginine) with the anionic centers of heparin. The action of protamine occurs immediately after intravenous administration and lasts 2 hours.

Enoxaparin sodium("Clexane") - low molecular weight heparin, rarely causes side effects - thrombocytopenia.

Fondaparinux sodium("Arixtra"), unlike heparin, causes thrombocytopenia in more rare cases.

Anticoagulants of indirect action. warfarin- one of the most commonly used anticoagulants. But it has a number of disadvantages:

• the risk of developing severe hemorrhagic complications;
• the need for regular laboratory control;
• drug and food interactions;
• narrow therapeutic range.

The new drugs are devoid of these side effects. Dabigatran etexilate is a strong competitive reversible direct inhibitor of thrombin. Rsharoxaban It is a selective direct factor Xa inhibitor that blocks the formation of thrombin. Used to prevent stroke and systemic thromboembolism in patients with atrial fibrillation.

fibrinolytics. Fibrinolytic drugs (fibrinolytics), as well as anticoagulants, are used to prevent and treat thrombosis. Streptokinase, urokinase, alteplase("Actilise") dissolve the clot (thrombolysis). This allows you to restore blood flow, limit the size of the infarct and reduce mortality. Thrombolysis is carried out as early as possible and within 12 hours from the onset of the disease.

Contraindications for all drugs that reduce blood clotting are bleeding, erosion and ulcers of the gastrointestinal tract, recent multiple injuries, arterial hypertension and other conditions that threaten bleeding.

International name: Blood Coagulation Factor IX (Coagulation Factor IX)

Dosage form:

Pharmachologic effect: Coagulation factor IX has a hemostatic effect; increases the concentration of factor IX in plasma, restores hemostasis in patients...

Indications: Bleeding caused by factor IX deficiency (treatment, prevention); hemophilia; bleeding caused by coumarin anticoagulants (before emergency surgery, in case of injury).

Benefix

International name: Nonacog alpha (Nonacog alfa)

Dosage form: lyophilisate for solution for intravenous administration

Pharmachologic effect: Recombinant coagulation factor IX from the serine protease family of vitamin K-dependent coagulation factors. Has a hemostatic effect; ...

Indications: Hemorrhagic complications in patients with hemophilia B (including during surgical interventions) - treatment and prevention.

Gemoctin SDT

International name:

Dosage form: lyophilisate for solution for infusion

Pharmachologic effect: The coagulation factor VIII molecule consists of 2 subunits (factor VIII and von Willebrand factor), which have different physiological ...

Indications: Prevention and treatment of bleeding in congenital (hemophilia A) and acquired deficiency of antihemophilic blood factor VIII. Treatment of inhibitory form of hemophilia A.

Hemostatic sponge with amben

International name:

Dosage form: sponge

Pharmachologic effect: Hemostatic agent for local use, inhibits tissue activators that convert profibrinolysin (plasminogen) into fibrinolysin (plasmin), ...

Indications: Capillary and parenchymal bleeding, bleeding from bones, muscles and other tissues, in cavities and on the surface of the body, incl. with a local boost...

Hemofactor NT

International name: Coagulation factors II, VII, IX and X in combination [Prothrombin complex] (Coagulation Factor II, VII, IX and X in combination)

Dosage form: lyophilisate for solution for infusion

Pharmachologic effect: A complex of blood coagulation factors, the action of which is based on the replacement of missing factors (II, VII, IX and X); has a hemostatic effect; restores hemostasis in patients with a deficiency of these factors.

Indications: Specific prevention and treatment of bleeding due to congenital deficiency of II, VII, IX and X coagulation factors (hypoprothrombinemia, ...

Hemophilus M

International name: Blood Coagulation Factor VIII (Coagulation Factor VIII)

Dosage form: lyophilisate for solution for infusion

Pharmachologic effect: Human antihemophilic factor (AHF) is a protein essential for normal blood clotting. The introduction of Hemophil M provides an increase in...

Indications: Hemophilia A (prevention and treatment of bleeding). Acquired coagulopathy caused by the presence of factor VIII inhibitors (when the concentration of inhibitors is not more than 10 BU / ml).

Gumbix

International name: Aminomethylbenzoic acid (Aminomethylbenzoic acid)

Dosage form: solution for intravenous and intramuscular administration, tablets

Pharmachologic effect: Hemostatic, antifibrinolytic agent, inhibits tissue activators that convert profibrinolysin (plasminogen) into fibrinolysin (plasmin), ...

Indications: Bleeding during surgical interventions and pathological conditions, accompanied by an increase in fibrinolytic activity of the blood (with ...

Dicynon

International name: Etamzilat (Etamsylate)

Dosage form:

Pharmachologic effect:

Indications:

Dicynon 250

International name: Etamzilat (Etamsylate)

Dosage form: solution for intravenous and intramuscular administration, tablets, tablets [for children]

Pharmachologic effect: Hemostatic agent; It also has an angioprotective and proaggregant effect. Stimulates the formation of platelets and their exit from the bone ...

Indications: Prevention and control of bleeding: parenchymal and capillary bleeding (including traumatic, in surgery during operations on severe ...

Idiopathic thrombocytopenic purpura (ITP) is a disease associated with a decrease in the number of peripheral blood platelets.

If this pathology becomes chronic, it doubly poisons the life of those who have bruises, spots on their skin for no reason, nosebleeds and other bleeding. The danger of thrombocytopenia lies in the fact that bleeding can be life threatening.

Traditional methods of treating an unpredictable disease do not always satisfy the doctor and the patient. Some give a short-term result, others do not give in to the disease.

Surgical intervention brings other troubles. Clinical trials have established that the most effective and safe stimulators of platelet production are thrombopoietin mimetics.

In the treatment of chronic ITP, one of the TPO receptor agonists - the drug "Revolade".

Benefits of the drug "Revolade"

Some of them are on a special account, and some can be purchased at a regular pharmacy. That is what the drug is. Kontrykal.

It belongs to a class of drugs designed to inhibit proteolytic enzymes.

The main area of ​​​​use of the drug is the treatment of pancreatitis of various types. With the elimination of this disease, 90% of patients and specialists are satisfied with the results.

Additionally, it is used when a person is in the stage of shock, since the active substance slows down the processes in the kallikrein-kinin system.

One of the representatives of such a drug group is an antifibrolitin (suppressive dissolution of a blood clot) agent. Amben.

1.2. MEDICINES AFFECTING COAGULATION

In the human body, the thrombogenic and thrombolytic systems are in a state of dynamic equilibrium. If the balance is disturbed, either increased bleeding or widespread thrombosis can occur. In such situations, drugs are prescribed, which, according to their pharmacological action, can be divided as follows:

1. Aggregates

2. Coagulants

A) direct action B) indirect action

3. Antifibrinolytic agents (fibrinolysis inhibitors)

1. Antiplatelet agents

2. Anticoagulants

3. Fibrinolytic (thrombolytic) agents

Means that help stop bleeding (hemostatics)

Aggregates. These are drugs that stimulate platelet aggregation. In practical medicine, calcium preparations and etamsylate are used. Calcium is directly involved in platelet aggregation. It is used in the form of calcium chloride or calcium gluconate for bleeding associated with a low content of calcium in the plasma (calcium chloride - strictly in / in!). Etamzilat activates the formation of thromboplastin. Used for capillary bleeding and angiopathy.

coagulants. These are drugs that increase blood clotting. A decrease in blood coagulation is observed with a decrease in the number of platelets, with liver diseases, with congenital inferiority of the blood coagulation system (hemophilia), with an overdose of anticoagulants. In such cases, hemorrhages in the mucous membranes and skin are observed. There is blood in the urine, and injuries and surgeries are accompanied by prolonged bleeding.

Direct acting coagulants include thrombin and fibrinogen.

Thrombin is a proteolytic enzyme involved in the formation of a fibrin thrombus. It is used only locally to stop bleeding from parenchymal organs and small capillaries.

Fibrinogen is a drug of local and systemic action; in the body turns into fibrin. Effective with low levels of fibrinogen in the blood. Used for bleeding during operations. with shocks, with hemophilia, in obstetric practice.

Indirect coagulants include vitamin K and its synthetic analogues.

Vitamin K is essential for the formation of clotting factors in the liver. For therapeutic purposes, phytomenadione is used - a fat-soluble natural vitamin K1; menadiol sodium phosphate and vikasol are synthetic analogues of vitamin K.

It is prescribed for bleeding caused by an overdose of indirect anticoagulants, with hypoprothrombinemia (due to cirrhosis, hepatitis, colitis), with the appointment of antibiotics that suppress the intestinal microflora.

Antifibrinolytic agents. These include aminocaproic acid, amben, tranexamic acid, contrykal, trasilol (aprotinin).

Acid a minocaproic I inhibits the formation of fibrinolysin, affecting the activators of this process, as well as directly inhibiting fibrinolysin. Ambene and tranexamic acid have similar effects.

Contric l and tra with ilol directly inhibit fibrinolysin and other proteolytic enzymes.

Fibrinolysis inhibitors are used for bleeding caused by an overdose of fibrinolytic agents, for uterine bleeding, for injuries and surgical operations.

In addition, preparations of various medicinal plants are used as hemostatic agents - lagohilus, nettle, yarrow, arnica.

Means for the treatment and prevention of thrombosis

Antiplatelet agents. These are medicinal substances that reduce platelet aggregation. The use of antiplatelet agents is currently the leading link in the prevention of thrombosis. Platelet aggregation is largely regulated by the thromboxane-prostacyclin system. Thromboxane A2 is synthesized in platelets and has a stimulating effect on their aggregation and causes vasoconstriction. Prostacyclin is synthesized mainly by the vascular endothelium, prevents platelet aggregation and causes vasodilation.

α-Cetylsalicylic acid in small doses (75-125 mg/day) inhibits thromboxane synthesis by inhibiting platelet cyclooxygenase (COX), which is more sensitive to the drug than vascular wall COX.

Ticlopidine inhibits ADP-induced platelet aggregation.

Clopidogrel inhibits platelet aggregation by blocking the binding of ADP to platelet membrane receptors.

Dipyride a mol inhibits phosphodiesterase and increases the content of c-AMP in platelets, due to which it has an antiplatelet effect. In addition, it potentiates the action of adenosine and prostacyclin, which have antiplatelet properties.

These drugs are used for therapeutic and prophylactic purposes in various forms of coronary artery disease, ischemic stroke, transient ischemic attacks, atrial fibrillation, obliterating atherosclerosis of the lower extremities, venous thrombosis and pulmonary embolism, after heart valve replacement surgery.

Anticoagulants. Prevent the formation of fibrin clots. They are classified into direct and indirect anticoagulants. Direct-acting anticoagulants inactivate circulating blood coagulation factors, are effective in vitro and in vivo, are used for blood conservation, treatment and prevention of thromboembolic diseases and complications. Anticoagulants of indirect action (oral) are vitamin K antagonists and disrupt the activation of coagulation factors in the liver, which is dependent on this vitamin, are effective only in vivo, and are used for therapeutic and prophylactic purposes.

Direct-acting anticoagulants include heparin, low molecular weight heparins (nadroparin-calcium, enoxaparin-sodium, etc.), sodium hydrocitrate.

Heparin is a physiological anticoagulant that affects all stages of blood coagulation, acts in combination with antithrombin III and is ineffective in its absence. In high doses, it disrupts platelet aggregation. Heparin also reduces the content of lipoproteins in the blood serum, has immunosuppressive properties. Applied topically and parenterally. When administered intravenously, the effect develops immediately and lasts up to 6 hours. It is used for the prevention and treatment of thrombosis and thromboembolism, for some autoimmune diseases (glomerulonephritis), in the complex treatment of atherosclerosis. The main complication in the use of heparin is bleeding, for the prevention of which it is necessary to constantly monitor the APTT or blood clotting time. In case of overdose, a specific heparin antagonist, protamine sulfate, is used.

Low molecular weight heparins affect the activity of thrombin to a lesser extent, therefore they cause bleeding less often.

Sodium hydrocitrate disrupts the formation of thrombin, because. binds Ca2+. Used as a stabilizer in blood preservation.

Anticoagulants of indirect action include: derivatives of 4-hydroxycoumarin ( neodicoumarin, sincumar, warfarin) and indandione derivatives (phenylin). Drugs are prescribed orally. They have a long latent period, so they are used for long-term treatment and prevention of thrombotic complications. All drugs cumulate. The most common complication with their use is bleeding, which requires control of INR (international normalized ratio) to prevent. Help with overdose - the abolition of the anticoagulant and the appointment of vitamin K preparations.

fibrinolytic agents. These are drugs that promote the lysis of fibrin thrombi. These drugs either activate the physiological system of fibrinolysis or replenish the missing fibrinolysin. There are direct-acting and indirect-acting fibrinolytics.

TO direct acting fibrinolytics includefibrinolysin and profibrinolysin. These drugs affect the breakdown of fibrin, contribute to the melting of blood clots and the restoration of normal blood flow. Profibrinolysin is able to penetrate into the thrombus, fibrinolysin acts on its surface.

TO indirect fibrinolytics include plasma (streptokinase and urokinase) and tissue (alteplase) plasminogen activators. These drugs affect fibrinolysis activators. Able to penetrate into the thrombus. A particularly good effect is achieved with the early use of drugs (in the first 12 hours after thrombus formation). The main side effect is bleeding, for the prevention of which it is necessary to control the fibrinolytic activity of the blood, the content

fibrinogen and profibrinolysin. With the introduction of streptokinase, allergic reactions are possible. Tissue plasminogen activator has a high selectivity for fibrin-bound plasminogen. In terms of thrombolytic efficacy, it surpasses plasma activators. Rarely causes bleeding and is devoid of antigenic properties.

Control questions

1. Why is it that small rather than large doses of acetylsalicylic acid dilate blood vessels and reduce platelet activity?

Acetylsalicylic acid irreversibly acetylates COX, i.e. permanently deprives this enzyme of activity. Platelets, on the other hand, are defective cells: being fragments of megakaryocytes, they lack the ability to synthesize new enzymes. Both in low and high doses, acetylsalicylic acid inactivates platelet and endothelial COX. Endothelial cells, unlike platelets, are able to synthesize new enzyme molecules. Therefore, the production of prostacyclins is only temporarily inhibited, while the formation of thromboxanes in platelets is blocked irreversibly. To resume their synthesis, the appearance of new platelets is necessary. As a result, blood vessels dilate and platelet aggregation decreases. At a high concentration of acetylsalicylic acid in the blood, both platelet and endothelial production of prostanoids is inhibited, since a new enzyme synthesized by endothelial cells is quickly acetylated (inactivated) under such conditions.

2. Compare the mechanisms of action of warfarin and heparin

Heparin very quickly prevents the formation of a blood clot, while warfarin begins to act slowly. Conversely, after discontinuation of heparin, blood clotting is quickly restored, while the effect of warfarin persists for several days after discontinuation of the drug.

Both substances indirectly affect the cascade of blood coagulation reactions. Heparin requires interaction with antithrombin III for its action, and the effect of warfarin is associated with a decrease in the level of vitamin K, which affects certain clotting factors.

3. Does warfarin work immediately? Explain.

No. The pharmacological effect of this substance appears after almost 4 hours. Before that, two things must happen.

The available reserves of vitamin K in the liver must be depleted. Under the influence of warfarin, the level of the vitamin first decreases only in the blood, so the anticoagulant effect is not immediately observed, since it requires the depletion of all reserves of the active form of vitamin K.

Activated platelet factors must have time to be metabolized. Already activated factors do not depend on the presence of vitamin K, so the effect of warfarin appears only after their inactivation.

4. What antidote is used for heparin overdose?

Protamine sulfate is used as an antidote. The molecules of this substance carry a high positive charge, due to which they bind strongly to negatively charged heparin molecules, preventing its pharmacological action.

5. Describe the mechanism of action of alteplase.

This drug binds to the fibrin of an already existing thrombus and activates the conversion of profibrinolysin to fibrinolysin (plasmin), which lyses fibrin. A thrombus devoid of a fibrin base disintegrates.

DRUGS. Heparin (Heparinum) - 5 ml bottles (1 ml - 5000 IU), protamine sulfate (Protamini sulfatis) - amp. 2% - 1 ml, warfarin (Warfarin) - tab. 2.5 mg, thrombin

(Trombin) - amp., containing 125 IU of the drug, fibrinogen (Fibrinogen) - amp., containing 1.0 dry matter, phytomenadione - caps. 0.01, streptokinase (Streptokinase)

- amp. 25,000 units of the drug, aminocaproic acid (Ac. aminocapronicum) - powder, 5%-100 ml vials.

TEST QUESTIONS Choose one correct answer

1. THROMBOXANE BIOSYNTHESIS INDICATION AGENT:

1. Dipyridamole

2. Ticlopidin

3. Acetylsalicylic acid

4. Clopidogrel

2. HEPARIN ANTAGONIST:

1. Protamine sulfate

2. Phytomenadione

3. Vikasol

3. clopidogrel and ticlopidine:

1. Inhibit phosphodiesterase

2. block thromboxane receptors

3. block ADP receptors on platelets

4. Increase the content of calcium ions in the cytoplasm of platelets

4. PROTHROMBIN SYNTHESIS IN THE LIVER STIMULATES:

1. Cyanocobalamin

2. Folic acid

3. Phytomenadione

4. Thiamine

5 Retinol

5. STEPTOKINASE STIMULATES THE TRANSITION: 1. Prothrombin to thrombin

2. fibrinogen to fibrin

3. Profibrinolysin to fibrinolysin

6. ALTEPLAZA:

1. Reduces blood clotting

2. Acts on fibrin and causes its dissolution

3. Activates fibrinolysis mainly in the thrombus

4. Activates the conversion of profibrinolysin to fibrinolysin in plasma

5. Reduces platelet aggregation

7. FOR BLEEDING ASSOCIATED WITH INCREASED FIBRINOLYSIS, APPLY:

1. Acid acetylsalicylic

2. Urokinase

3. Acid-aminocaproic

8. IN OVERDOSE OF INDIRECT-ACTING ANTICOAGULANTS IT IS EFFECTIVE:

1. Phytomenadione

2. Contrykal

3. Protamine sulfate

9. ANTIAGGREGANT AND CORONARY DILATIVE ACTION IS CHARACTERISTIC FOR:

1. Acetylsalicylic acid

2. Ticlopidine

3. Clopidogrel

4. Dipyridamole

10. DIRECT ACTING ANTICOAGULANTS:

1. Cause thrombus lysis

2. Only effective in vivo

3. Used to prevent thrombosis

4. Effective when taken orally

1.3. ANTIHYPERTENSIVE DRUGS (AGS)

AGS includes drugs from different pharmacological groups that can lower high blood pressure (BP).

They are used to treat diseases of the cardiovascular system, accompanied by circulatory disorders and increased blood pressure (both in individual vascular areas and in the whole body).

The regulation of blood pressure is influenced by many factors, among which three main ones can be distinguished: cardiac output (determined by strength and heart rate), total peripheral vascular resistance, and circulating blood volume.

AGS are not the same in terms of localization and mechanism of action and are classified taking into account these features.

A . AGS neurotropic action

I. Central:

1) reducing the excitability of vasomotor centers and centers of sympathetic innervation: clonidine (clophelin), methyldopa (dopegyt), moxonidine (cint).

2) non-specific action: tranquilizers, hypnotics in small doses (see relevant sections)

II. Peripheral:

1) ganglion blockers: azamethonium (pentamine), hexamethonium benzosulfonate(benzohexonium)

2) sympatholytics: reserpine, guanethidine (octadine)

3) blockers

a) α-β-blockers: carvedilol (dilatrend)

b) α-blockers: non-selective (α1α2) action (tropodifen (tropafen), phentolamine) and selective (α1) action (prazosin (minipress), doxazosin)

c) β-blockers: non-selective (β1β2) action (propranolol (anaprilin), and selective (β1) action (atenolol (tenormin), metoprolol).

B . AGS of myotropic action:

1) NO donators: sodium nitroprusside

2) Calcium channel blockers: nifedipine (fenigidin, corinfar), amlodipine (Norvasc)

3) K+ channel activators: diazoxide (hyperstat), minoxidil (loniten)

4) Other myotropic AGS: hydrazan (apressin), bendazol (dibazol), magnesium sulfate

B. RAAS inhibitors

Vikasol is a synthetic water-soluble analogue of vitamin K. It helps to stop only such bleeding, which is caused by a low content of prothrombin in the blood due to vitamin K deficiency. Vikasol stimulates the synthesis of prothrombin by liver cells, it is indicated for bleeding caused by a low content of prothrombin, for example, with hepatitis, cirrhosis, obstructive jaundice, renal-hepatic syndrome, as well as with an overdose of "indirect" anticoagulants (neodicoumarin, pelentan, etc.). It has some effect on ulcerative, bleeding, juvenile and menopausal uterine bleeding. Ineffective in hemophilia and Werlhof's disease.

The effect of the drug occurs no earlier than 12-18 hours after administration to the body. Vikasol is produced in tablets of 0.015 g and in ampoules of 1 ml of a 1% solution. Vikasol is prescribed per os at 0.015 g 2-3 times a day, intramuscularly at 1 ml of a 1% solution 1-2 times a day for no more than 4 days in a row (due to the risk of thrombosis). Vikasol is contraindicated in patients with increased blood clotting, thrombophlebitis, acute myocardial infarction.

Vitamin P - a complex of tea catechins - inhibits the action of hyaluronidase, which dissolves the connective tissue base of the capillary wall, thereby somewhat reducing the permeability and fragility of capillaries. In addition, vitamin P protects ascorbic acid from oxidation in the body, which also strengthens the capillary wall. The most common vitamin P preparation is rutin, a greenish-yellow, water-insoluble powder. Rutin to a certain extent reduces the severity of skin hemorrhagic rash in capillary toxicosis and Werlhof's disease. The drug is also used for retinal hemorrhages, septic endocarditis, measles, scarlet fever. Vitamin P practically does not cause thrombosis, there are no contraindications to its use. The drug is available in tablets of 0.02. g and in complex with ascorbic acid (ascorutin): 0.05 g of rutin and 0.05 g of ascorbic acid. Rutin is prescribed for adults in doses of 0.02-0.05 g 3-4 times a day.

Epsilon-aminocaproic acid is a white crystalline powder, odorless and tasteless, highly soluble in water. It has a powerful hemostatic effect (general and local), inhibiting the activity of the fibrinolytic system of the blood. In addition, the drug reduces the tryptic activity of digestive juices. Epsilon-aminocaproic acid is indicated for nasal, gingival, gastric, intestinal, renal, uterine bleeding of various etiologies, including Werlhof's disease, aplastic anemia, hemophilia, after curettage of the uterus. In a hospital, it is prescribed after operations on the lungs, prostate, with premature detachment of a normally located placenta. The drug is used orally 3.0-5.0 g 3-4 times a day, the powder is washed down with sweet water. Epsilon-aminocaproic acid is also administered intravenously (drip and jet) in 100 ml and more than 5% solution (daily dose 10-20 g). The drug is also successfully used for local hemostasis, abundantly powdering the bleeding area of ​​the nasal mucosa, the tooth socket after its extraction, etc. When taken orally, epsilon-aminocaproic acid does not irritate the digestive tract, in rare cases, patients report nausea. The maximum hemostatic effect is observed 1-4 hours after intravenous administration of the drug.

Contraindications to the use of epsilon-aminocaproic acid - thrombosis, acute renal failure.

Available in powder and bottles of 100 ml of a 5% solution.

Medical gelatin is a collagen hydrolyzate, which is a yellowish leaflet or a gelatinous colorless mass. When administered intravenously, gelatin increases blood viscosity and platelet stickiness, providing a very good and rapid hemostatic effect in internal bleeding (including gastrointestinal, intrapleural, etc.), and is less effective in bleeding mucous membranes. Side effect - allergic phenomena. The drug is mainly used intravenously in drops of 50-100 ml or more of a solution heated to 37°C. Release form: 10 ml ampoules of 10% gelatin solution in 0.5% sodium chloride solution.

Fibrinogen - (type M2 or K3) - a human blood product, I coagulation factor. Fibrinogen is used for "afibrinogenemic" bleeding intravenously (up to 1.8-2.0 g of dry matter per day). In practice, in most cases, it is necessary to inject epsilon-aminocaproic acid in parallel with fibrinogen in order not to provoke widespread blood microcoagulation (for example, in the postpartum period and during shock).

Immediately before use, fibrinogen powder is dissolved in 200–300 ml of warm (25–30°C) sterile saline, the infusion must be performed with a filter in the system, since insoluble protein particles may appear in the drug solution.

Contraindications to the use of fibrinogen - thrombophlebitis, acute myocardial infarction.

Sometimes with internal bleeding, a direct blood transfusion or infusion of freshly citrated blood (i.e., stored for less than 1 day) gives a good effect. Dry plasma or specially prepared (in the cold) its concentrate - cryoprecipitate - ensure the stop of hemophilic bleeding.

The best way to stop bleeding caused by a lack of platelets (with Werlhof's disease, aplastic anemia, radiation sickness, etc.) is the transfusion of fresh platelet mass prepared in plastic bags on a blood cell separator in the conditions of hematological centers. Bleeding in this case stops "on the needle", i.e. during the infusion of the mass. The preparation of platelet mass in glass vessels by “removing the film” does not ensure the safety of platelets and, therefore, eliminates the hemostatic effect.

Trasilol (synonyms: tsalol, kontrikal) is a preparation of the parotid glands of cattle that inhibits the process of intravascular microcoagulation and breaks down trypsin. It is used for bleeding observed with extensive tissue injuries, after septic abortion, with acute leukemia (for example, promyelocytic) and other conditions, 10,000-20,000 IU intravenously drip 1-2 times a day in 5% glucose solution or saline. As a rule, trasylol is administered in a hospital. In addition, the drug is widely used in acute and chronic pancreatitis, mumps. Side effects - allergies (up to anaphylactic shock), phlebitis at the injection site.

Release form: 5 ml ampoule (25,000 IU) of the drug solution.

Protamine sulfate is a protein derivative capable of forming insoluble complexes with heparin and thromboplastin. It is used for hemorrhages caused by hyperheparinemia (due to an overdose of heparin or hyperproduction of endogenous heparin). The drug provides a quick (within 1-2 hours) stop bleeding. Usually, 5 ml of a 1% solution of protamine sulfate is administered intravenously or intramuscularly, if necessary, the administration is repeated after 15 minutes.

In the process of treatment with protamine sulfate, it is necessary to control the time of blood clotting. The drug is available in 5 ml ampoules of a 1% solution.

Hemophobin is a pectin solution that has a weak hemostatic effect in hemorrhoidal, uterine and other bleeding. Apply intramuscularly in 5 ml of a 1.5% solution and topically (for example, in the hole after tooth extraction). Inside the drug is prescribed 1 tablespoon 2-3 times a day.

Release form: in ampoules of 5 ml, in vials of 150 ml for internal use and for wetting tampons.

Adroxon is an odorless and tasteless orange powder. It is effective for capillary bleeding as a result of minor injuries, after tonsillectomy, tooth extraction, etc. A 0.025% solution of adroxon is used to wet tampons, as well as for intramuscular injections (1 ml of a 0.025% solution) many times before surgery, during it and in the postoperative period . Adroxon is also effective in gastrointestinal bleeding.

Produced in ampoules of 1 ml of 0.025% solution.

Etamsylate (dicynone) improves platelet function, reduces capillary permeability. Effective for the prevention and treatment of capillary bleeding during tonsillectomy, tooth extraction, pulmonary and intestinal bleeding. The maximum effect lasts 1-2 hours with intravenous administration and 3 hours with oral administration.

Prophylactically, etamzilat is used in 2-4 ml intramuscularly or 2-3 tablets per os. In case of bleeding, 2-4 ml of the drug is administered intravenously or intramuscularly and then 2 ml every 4 hours.

Etamzilat is produced in ampoules of 2 ml of a 12.5% ​​solution and in tablets of 0.25 g.

Some substances contained in plants also have a moderate hemostatic property. The history of their application has more than one century.

Tincture of lagohilus (hare lip) intoxicating (Tinctura Lagochilli inebrians) contains latochiline and tannins, has a moderate stimulating effect on the blood coagulation system and gives a slight sedative effect. It is recommended as a symptomatic remedy for mild recurrent nasal, hemorrhoidal and uterine (hypermenorrhea) bleeding orally, 1 teaspoon of 10% tincture per 0.25 glass of water 3-4 times a day. Side effect - moderate laxative effect. Swabs moistened with tincture of lagohilus can also be used to locally stop nasal or hemorrhoidal bleeding.

Release form: 10% alcohol tincture.

Liquid nettle leaf extract (Extr. Urticae fluidum) contains ascorbic acid, vitamin K and tannins, has a moderate hemostatic effect in uterine, renal, intestinal bleeding due to local causes and in Werlhof's disease. Assign inside 25-30 drops of the extract 3 times a day 30 minutes before meals.

Yarrow herb liquid extract (Extr. Millefolii fluidum) contains alkaloids, ascorbic acid, tannins and resins; gives a weak hemostatic effect in uterine bleeding. Assign 40-50 drops of the extract 3 times a day, usually in combination with an extract of nettle leaves (to enhance the hemostatic effect).