Anticoagulant drugs list. What are anticoagulants in medicine, their classification and names of drugs. Simultaneous food intake

In drug therapy, anticoagulants are used to prevent blood clotting. For diseases directly or indirectly related to thrombus formation, they can be considered vital. The list of anticoagulant drugs includes direct and indirect drugs.

Prescribed for treatment:

• Acute venous and arterial thrombosis.
• Pathologies associated with the release of large amounts of thromboplastic substances from tissues.
• After previous operations to prevent the formation of blood clots.
• As a preventive measure in the presence of heart disease.

What drugs are classified as anticoagulants? These medications have blood thinning properties and are also called anticoagulants. They are divided into two groups: direct and indirect action.

List of direct anticoagulant drugs

This group includes antithrombolic medications that reduce the clotting factor (thrombin) in the blood.

1. Heparins for topical use (externally).

These drugs, related to anticoagulants, are prescribed for internal inflammation of the veins with the formation of a blood clot in their cavity.

Stop the inflammatory process. Reduce platelet aggregate formation and thrombin activity. Relieves swelling. Activate tissue respiration. They help dissolve blood clots and gradually restore the lumen of the veins. Reduces painful sensations.

The list includes direct anticoagulant drugs Russian production:

1. Heparin ointment 25 g - 50 rubles.
2. Heparin-Akrikhin 1000 gel 30 g - 224 rub.
3. Trombless gel 30 g - 249 rub.
4. Venolife 40 grams - 330 rub.
5. Laventum 50 g - 290 rubles.

For subcutaneous and intravenous administration

Anticoagulant drugsare used in the treatment of deep vein thrombosis, pulmonary artery thrombolism, and angina pectoris. They are thrombin blockers. Prevents the formation of non-globular fibrin protein and platelet aggregation.

As a therapeutic therapy, the doctor prescribes:

1. Clexane (France). Main active ingredient enoxaparin sodium prevents blockage of blood vessels by a thrombus and the formation of blood clots.

• Syringes 0.2 ml 10 pcs. - 1700 rubles.

2. Fraxiparine (France). Active substance nadroparin calcium has high factor Xa activity. Used to thin the blood when there is a risk of thrombosis.

• Syringes 2850 ME 0.3 ml 10 pcs. - 2150 rub.

3. Fragmin (USA). Prescribed to patients undergoing hemodialysis or hemofiltration. An effective blood anticoagulant. Active substance of the solution alteparin sodium has an anticoagulant effect. Reduces the rate of chemical reactions of blood clotting factor and thrombin.

• Solution 2500 anti-Xa ME/0.2 ml 10 pcs. - 2100 rubles.

Indirect anticoagulant drugs

The active substances of medications included in this group disrupt the synthesis of prothrombin in the liver and slow down the blood clotting process. Prothrombin is a precursor to the enzyme thrombin. Refers to complex blood plasma proteins. Participates in blood clotting with the participation of vitamin K.

List of anticoagulant drugs in tablets

1. Warfarin (Russia). The most popular drug from the list of indirect anticoagulants for the treatment of thrombosis of the venous system. Reduces the likelihood of thromboembolic complications.

If you follow a diet, constantly monitor your blood for INR and dosage, therapy leads to positive results. The affordable price is another significant advantage of the medication.

• Tab. 2.5 mg 50 pcs. - 86 rubles.

2. Fenilin (Russia). Another indirect anticoagulant drug is an effective remedy in tablet form. Active substance phenindione has anticoagulant properties.

Prescribed for blockage of the walls of veins, vessels of the lower extremities and brain. It is used as a preventive measure after surgical interventions.

• Packaging tab. 20 mg 30 pcs. - 120 rub.

3. Sinkumar (Russia). The drug is included in the list of coumarin anticoagulant drugs. Prevents the synthesis of vitamin K into its active form, as a result of which the coagulation process (formation of blood clots) is disrupted. Suppresses the synthesis of blood clotting factors.

• Packaging tab. 2 mg 50 pcs. - 470 rub.

New generation anticoagulants

A feature of the drugs is the ability not to constantly monitor the blood clotting index (INR). Judging by this property, the new drugs are superior to Warfarin in ease of use. However, the high price of drugs limits their availability, which is a significant drawback.

The list of new generation anticoagulant drugs includes:

1. Xarelto (Germany). The active component of medicines is rivaroxaban. Clinical studies have proven the high effectiveness of this product. Easy to use. Does not tie patients to constant testing.

• Cost of 15 mg tablet 28 pcs. - 2700 rub.

2. Eliquis (USA). Main active ingredient apixaban restores vein patency. Used for the prevention of cardioembolic stroke. Does not require systematic monitoring of hemostasis.

• Price of tablets 5 mg 60 pieces - 2400 rub.

3. Pradaxa (Austria). The main component of the medicine dabigatran etexilate. Prescribed for venous and systemic thromboembolism, including damage to the pulmonary artery after severe injuries and complex operations.

Well tolerated. During drug therapy, practitioners note a low risk of bleeding.

• Capsules 110 mg 30 pcs. - 1750 rubles.

They are divided into natural anticoagulants and synthetic ones. The former are produced in the body, the latter are produced artificially and are used in medicine as medicines.

Natural

They can be physiological and pathological. Physiological anticoagulants are normally present in plasma. Pathological ones appear in the blood in some diseases.

Physiological anticoagulants are divided into primary and secondary. Primary ones are synthesized by the body independently and are constantly in the blood. Secondary ones are formed during the breakdown of coagulation factors during the formation of fibrin and its dissolution.

Primary natural anticoagulants

They are usually divided into groups:

1. Antithromboplastins.
2. Antithrombins.
3. Inhibitors of fibrin self-assembly.

When the level of primary physiological anticoagulants in the blood decreases, there is a risk of developing thrombosis.

This group of substances includes:

• Heparin. It is a polysaccharide synthesized in mast cells. It is found in significant quantities in the lungs and liver. In large doses, it interferes with the blood clotting process at all stages and suppresses a number of platelet functions.
• Antithrombin III. Synthesized in the liver, it belongs to alpha₂-glycoproteins. Reduces the activity of thrombin and some activated coagulation factors, but does not affect non-activated factors. The anticoagulant activity of plasma is 75% provided by antithrombin III.
• Protein C. It is synthesized by liver parenchyma cells and is in an inactive form in the blood. Activated by thrombin.
• Protein S. Synthesized by endothelial cells and liver parenchyma (hepatocytes), depends on vitamin K.
• Alpha₂-macroglobulin.
• Antithromboplastins.
• Contact inhibitor.
• Lipid inhibitor.
• Complement inhibitor-I.

Secondary physiological anticoagulants

As already mentioned, they are formed during the process of blood coagulation and the dissolution of fibrin clots during the breakdown of certain coagulation factors, which, due to degradation, lose their coagulation properties and acquire anticoagulation properties. These include:

• Antithrombin I.
• Antithrombin IX.
• Metafactors XIa and Va.
• Febrinopeptides.
• Auto-II anticoagulant.
• Antithromboplastins.
• PDF are products formed during the breakdown (degradation) of fibrin under the influence of plasmin.

Pathological anticoagulants

In some diseases, specific antibodies can form and accumulate in the blood, preventing blood clotting. They can be produced against any coagulation factors, but inhibitors of factors VIII and IX are most often produced. In some autoimmune diseases, pathological proteins appear in the blood that have an antithrombin effect or suppress coagulation factors II, V, Xa.

Anticoagulant drugs

Artificial anticoagulants, of which a large number have been developed, are indispensable drugs in modern medicine.

Indications for use

Indications for taking oral anticoagulants are:

• myocardial infarction;
• pulmonary infarctions;
• heart failure;
• thrombophlebitis of the leg veins;
• thrombosis of veins and arteries;
• phlebeurysm;
• thrombotic and embolic strokes;
• embolic vascular lesions;
• chronic aneurysm;
• arrhythmias;
• artificial heart valves;
• prevention of atherosclerosis of blood vessels in the brain, heart, and peripheral arteries;
• mitral heart defects;
• thromboembolism after childbirth;
• prevention of thrombosis after surgery.

Heparin is the main representative of the class of direct anticoagulants

Classification of anticoagulants

Medicines in this group are divided into direct and indirect depending on the speed and mechanism of action, as well as the duration of the effect. Direct directly affect blood clotting factors and inhibit their activity. Indirect ones act indirectly: they slow down the synthesis of factors in the liver. Available in tablets, injection solutions, and ointment form.

Direct

Medicines in this group act directly on coagulation factors, which is why they are called fast-acting drugs. They prevent the formation of fibrin threads, prevent the formation of blood clots and stop the growth of existing ones. They are divided into several groups:

• heparins;
• hirudin;
• low molecular weight heparin;
• sodium hydrogen citrate;
• danaparoid, lepirudin.

Heparin ointment is excellent against bruises and is used to treat thrombophlebitis and hemorrhoids

This is the most famous and widespread direct-acting anticoagulant. It is administered intravenously, subcutaneously and intramuscularly, and is also used as a topical ointment. Heparin-type drugs include:

Topical heparins have low tissue permeability and are not very effective. Used to treat varicose veins of the legs, hemorrhoids, and bruises. The most well-known and often used are the following heparin products:

Lyoton is a popular heparin-containing agent for external use for varicose veins.

Heparins for intravenous and subcutaneous administration are a large group of medications that are selected individually and are not replaced by one another during the treatment process, since they are not equivalent in action. The activity of these drugs reaches its maximum after about three hours, and the effect continues throughout the day. These heparins reduce the activity of tissue and plasma factors, block thrombin, prevent the formation of fibrin threads, and prevent platelet aggregation.

For the treatment of deep vein thrombosis, heart attack, pulmonary embolism, and angina, Nadroparin, Enoxaparin, and Deltaparin are usually prescribed.

To prevent thromboembolism and thrombosis, Heparin and Reviparin are prescribed.

This anticoagulant is used in laboratory practice. To prevent blood from clotting, it is added to test tubes. It is used for the preservation of blood and components.

Indirect

They reduce the production of certain coagulation factors in the liver (VIII, IX, X, prothrombin), slow down the formation of proteins S and C, and block the production of vitamin K.

These include:

1. Indan-1,3-dione derivatives. Representative - Fenilin. This oral anticoagulant is available in tablets. Its action begins 8 hours after administration, reaching maximum effectiveness within a day. During administration, it is necessary to monitor the prothrombin index and check the urine for the presence of blood in it.
2. Coumarin. In the natural environment, coumarin is found in plants (bison, sweet clover) in the form of sugars. For the first time, its derivative, dicoumarin, which was isolated in the 20s of the 20th century from clover, was used to treat thrombosis.

Indirect anticoagulants include the following drugs:

Warfarin should not be taken in case of certain kidney and liver diseases, thrombocytopenia, acute bleeding and tendency to bleed, during pregnancy, lactase deficiency, congenital deficiency of proteins C and S, disseminated intravascular coagulation syndrome, if the absorption of galactose and glucose is impaired.

Warfarin is the main representative of the class of indirect anticoagulants

Side effects include abdominal pain, vomiting, diarrhea, nausea, bleeding, urolithiasis, nephritis, alopecia, allergies. A skin rash, itching, eczema, and vasculitis may appear.

The main disadvantage of Warfarin is the high risk of bleeding (gastrointestinal, nasal and others).

New generation oral anticoagulants (NOACs)

Modern anticoagulants are an indispensable means for the treatment of many diseases, such as heart attacks, thrombosis, arrhythmias, ischemia and many others. Unfortunately, drugs that have proven to be effective have many side effects. But developments do not stop, and new oral anticoagulants periodically appear on the pharmaceutical market. PLAs have both advantages and disadvantages. Scientists are trying to obtain universal remedies that can be taken for various diseases. Drugs are being developed for children, as well as for patients for whom they are currently contraindicated.

New anticoagulants have the following advantages:

• when taking them, the risk of bleeding is reduced;
• the effect of the medicine occurs within 2 hours and quickly ceases;
• the drugs can be taken by patients for whom Warfarin is contraindicated;
• the influence of other drugs and food consumed is reduced;
• inhibition of thrombin and thrombin-binding factor is reversible.

The new drugs also have disadvantages:

• many tests for each product;
• it is necessary to drink regularly, while old medications can be skipped due to their long-term effects;
• intolerance by some patients who had no side effects when taking the old pills;
• risk of bleeding in the gastrointestinal tract.

As for indirect anticoagulants, they have not yet been developed that are radically different from Warfarin, Dicumarin, and Sinkumar.

New drugs Apixaban, Rivaroxaban, Dabigatran may become an alternative for atrial fibrillation. Their main advantage is that they do not require constant blood donation while taking them, and they do not interact with other medications. At the same time, these drugs are just as effective and can prevent stroke due to arrhythmia. As for the risk of bleeding, it is either the same or lower.

What you need to know

Patients prescribed oral anticoagulants should be aware that they have a large number of contraindications and side effects. When taking these medications, you need to follow a diet and take additional blood tests. It is important to calculate your daily dose of vitamin K, since anticoagulants interfere with its metabolism; Regularly monitor laboratory indicators such as INR (or INR). The patient should know the first symptoms of internal bleeding in order to seek help in time and change the drug.

Antiplatelet agents

Medicines in this group also help thin the blood and prevent the formation of blood clots, but their mechanism of action is different. Antiplatelet agents reduce blood clotting due to their ability to inhibit platelet aggregation. They are prescribed to enhance the effect of anticoagulants. In addition, they have an antispasmodic and vasodilating effect. The most popular antiplatelet agents:

• Aspirin is the most famous of this group. It is considered a very effective remedy that dilates blood vessels, thins the blood and prevents the formation of blood clots.
• Tirofiban – prevents platelet aggregation.
• Ticlopidine is indicated for cardiac ischemia, heart attacks, and for the prevention of thrombosis.
• Dipyridamole is a vasodilator.
• Eptifibatitis – blocks platelet aggregation.

Aspirin is the most famous representative of the group of antiplatelet drugs

A new generation of drugs includes the drug Brilint with the active substance ticagrelor. It is a reversible antagonist of the P2Y receptor.

Natural blood thinners

Adherents of traditional treatment methods use herbs with a blood-thinning effect to prevent thrombosis. The list of such plants is quite long:

• horse chestnut;
• willow bark;
• mulberry;
• sweet clover;
• wormwood;
• meadowsweet:
• Red clover;
• liquorice root;
• evasive peony;
• chicory and others.

Before using herbs, it is advisable to consult a doctor: not all plants can be beneficial.

Red clover is used in folk medicine as a means to improve blood flow.

Conclusion

Anticoagulants are indispensable drugs for the treatment of cardiovascular pathologies. You cannot take them on your own. They have many contraindications and side effects, and uncontrolled use of these medications can lead to bleeding, including hidden bleeding. They should be prescribed and the dosage determined by a doctor who is able to take into account all the features of the course of the disease and possible risks. During treatment, regular laboratory monitoring is required.

It is important not to confuse anticoagulants and antiplatelet agents with thrombolytic agents. The main difference is that the former cannot destroy a blood clot, but only prevent or slow down its development. Thrombolytics are intravascular drugs that dissolve blood clots.

In one case, it is indicated that chicory, along with greens, should be removed from the diet, and chicory is named in the list of natural remedies (coagulants). So how do you know whether it can be taken in parallel with warfarin or not?

List of drugs - direct and indirect anticoagulants, blood thinners

In a healthy human body, the blood coagulation and anticoagulation systems are in dynamic equilibrium. At the same time, the flow of blood through the vessels is not hampered, and there is no excessive thrombus formation, both during open bleeding and inside the vascular bed.

When this balance is disturbed, conditions are created for thrombosis of small or large vessels or even the development of disseminated intravascular coagulation syndrome, in which multiple blood clots can lead to rapid death.

However, a number of clinical situations lead to blood clots forming in the wrong place and at the wrong time, clogging veins and arteries of different sizes.

Diseases in which coagulability is increased

Acute venous thrombosis

• Against the background of varicose veins of the lower extremities, phlebitis as a postoperative complication
• Thrombosis of hemorrhoidal veins
• Thrombosis in the inferior vena cava system

Acute arterial thrombosis

• Pulmonary embolism (PE)
• Ischemic stroke
• Myocardial infarction
• Acute injuries of the arteries of the lower extremities against the background of atherosclerosis, inflammation, vascular injury

Disseminated intravascular coagulation syndrome due to:

• injuries
• sepsis due to the release of a large number of blood clotting factors from tissues.

Treatment of all of these pathologies involves the use of anticoagulants, which are also called anticoagulants or blood thinners. These are medications designed to reduce blood clotting and thereby restore its fluidity (rheological properties) and reduce the risk of recurrent thrombosis. Anticoagulants reduce the activity of tissue (fibrinogen, platelets) or plasma coagulation factors. The effect of anticoagulants can be:

• direct - direct anticoagulants
• indirect - indirect anticoagulants

Prevention of heart diseases - in addition to the treatment of acute thrombosis, treatment with anticoagulants is carried out for their prevention in case of unstable angina, various heart rhythm disturbances (a permanent form of atrial fibrillation), for heart valve defects, obliterating endarteritis, for patients on hemodialysis, after reconstructive operations not on the heart (for example , coronary artery bypass surgery).

The third area of ​​​​use of anticoagulants is the stabilization of blood components when it is collected for laboratory tests or prepared for subsequent transfusion.

Direct anticoagulants

Topical heparins

They are characterized by low tissue permeability and a weaker effect. Used for local treatment of varicose veins, hemorrhoids, resorption of hematomas. List: Heparin ointment, Venolife, Lyoton gel, Venitan, Laventum, Trombless.

• Heparin ointment

• Lyoton gel

• Trombless gel

• Lavenum gel

• Venolife

(Heparin + Dexpanthenol + Troxerutin) 40g. 400 rub.

• Hepatrombin

Heparin+ Allantoin+ Dexpanthenol 40g. 300IU ointment 50 rubles, 500IU 40g. gel 300 rub.

• Venitan Forte gal

(heparin+escin) price 50 g. 250 rub.

• Troxevasin NEO

(Heparin + Dexpanthenol + Troxerutin) 40 gr. 280 rub.

Heparins for intravenous and subcutaneous administration

The second large group of direct anticoagulants are heparins, the mechanism of action of which is based on a combination of inhibition of plasma and tissue coagulation factors. On the one hand, these direct anticoagulants block thrombin and inhibit fibrin formation.

On the other hand, they reduce the activity of plasma coagulation factors (IXa, Xa, XIa, XIIa) and kallikrein. In the presence of antithrombin III, heparin binds to plasma proteins and neutralizes coagulation factors. Heparins destroy fibrin and inhibit platelet adhesion.

The drugs are administered subcutaneously or intravenously (depending on the instructions). During treatment, one drug does not change to another (that is, the drugs are not equivalent and are not interchangeable). The maximum activity of the drug develops after 2-4 hours, and activity persists throughout the day.

• Low molecular weight heparins

They have less effect on thrombin, predominantly inhibiting coagulation factor Xa. This improves the tolerability and effectiveness of low molecular weight heparins. They reduce platelet aggregation less than low molecular weight heparin anticoagulants. List of drugs:

• Fraxiparine

(Nadroparin calcium) 1 syringe 380 rub.

• Hemapaxan

(Enoxaparin sodium) 0.4 ml. 6 pcs. 1000 rub.

• Clexane

(Enoxaparin sodium) 0.4 ml 1 spr. 350 rub., Anfiber, Enixum

(Deltaparin sodium) 2500IU 10 pcs. 1300 rub. 5000IU 10 pcs 1800 rub.

• Klivarin

• Troparin

• Medium molecular weight heparins

These are the sodium and calcium salts of heparin. Heparin, Heparin Ferein 5 amp.rub.

How are heparins selected?

• For the prevention of thrombosis and thromboembolism (including postoperative ones), Klivarin and Troparin are preferred.
• For the treatment of thrombotic complications (unstable angina, heart attack, pulmonary embolism, deep vein thrombosis) - Fraxiparine, Fragmin, Clexane.
• For the prevention of thrombosis in patients on hemodialysis: Fraxiparine, Fragmin.

Cybernine – antithrombin III drug

Its action is similar to heparin: it blocks thrombin, coagulation factors IXa to XIIa, and plasmin. During treatment, the level of antithrombnia III in the blood plasma should be monitored.

Indications: The drug is used for thromboembolic complications due to congenital deficiency of antithrombin III or its acquired deficiency (against the background of liver cirrhosis with hepatic cell failure and severe jaundice, with disseminated intravascular coagulation syndrome, in patients receiving hemodialysis, with thromboembolism of various origins). The drug is prescribed intravenously.

Contraindications: Cybernine is not used in children intolerant to it. Use with caution in pregnant women.

Side effects: Its use may be complicated by skin allergies (urticaria), dizziness, breathing problems, chills, fever, unpleasant taste in the mouth, blurred vision, cough, chest pain.

Direct acting antithrombotics

They work by directly blocking thrombin (a plasma clotting factor that is formed from prothrombin activated by thromboplastin). The drugs in this group work similarly to hirudin, secreted by leeches and preventing blood clotting.

• Recombinant natural hirudins (Desirudin, Lepirudin) block the active region of thrombin and fibrin.
• The mechanism of action of synthetic hirudin (Bivalirudin) is similar to them.
• Melagatran and Efegatran carry out an isolated covalent blockade of the active part of thrombin.
• Argatroban, Dabigatran, Ximelagatran, Inogatran, Etexipat carry out an isolated non-covalent blockade of thrombin.

Ximelagatran has been associated with great promise in the prevention of strokes. In experiments, it showed decent results and was not inferior in effectiveness and bioavailability to Warfarin. However, further evidence has accumulated that the drug causes serious liver damage, especially with long-term use.

Fondaparinux (Arixtra) is a direct-acting parenteral anticoagulant that selectively inhibits coagulation factor Xa. It can be administered subcutaneously without APTT monitoring in standard doses, taking into account the patient’s body weight. The average dose is 2.5 mg per day.

The drug is excreted mainly by the kidneys, unchanged.

Used for the prevention of thromboembolic complications in patients undergoing major abdominal surgery, in long-term immobilized patients or patients undergoing joint replacement. The drug treats acute deep vein thrombosis of the lower extremities, pulmonary embolism, and acute coronary syndrome.

The next direct anticoagulant is sodium hydrocytart

It is used exclusively for the preservation of blood and its components. This is what is added to test tubes with blood in the laboratory to prevent it from clotting. By binding free calcium ions, sodium hydrogen citrate prevents the formation of thromboplastin and the conversion of prothrombin to thrombin.

Indirect anticoagulants

Indirect anticoagulants are drugs that have the opposite effect of vitamin K. They either reduce the formation of proteins (proteins C and S) involved in the anticoagulant system, or impede the formation of prothrombin, VII, IX and X coagulation factors in the liver.

Indan-1-3dione derivatives are represented by Phenilin (Phenidion)

• The drug is available in tablets of 0.03 grams (20 pieces, 160 rubles).
• The drug works within 8-10 hours of administration. The maximum effect occurs after an hour. It accumulates in the body less than warfarin and does not produce the effect of the total dose. Less effect on capillaries. Prescribed under the supervision of PTI.
• It is prescribed one tablet in four doses on the first day, on the second day one tablet in three doses, then one tablet per day (depending on the level of IPT). In addition to monitoring IPT, urine tests should be performed to check for the appearance of red blood cells.
• Does not combine well with hypoglycemic agents (Butamide).

Coumarin derivatives

In nature, coumarin in the form of sugars is found in many plants (aster, sweet clover, bison). In its isolated form, these are crystals that smell like fresh hay. Its derivative (dicoumarin) was isolated in 1940 from rotting sweet clover and was first used to treat thrombosis.

This discovery of pharmacists was prompted by veterinarians who, in the 20s of the last century, discovered that cows in the USA and Canada, grazing in meadows overgrown with clover, began to die from massive bleeding. After this, dicoumarin was used for some time as a rat poison, and later began to be used as an anti-clotting drug. Subsequently, dicoumarin was replaced from pharmaceuticals by neodicoumarin and warfarin.

List of drugs: Warfarin (Warfarex, Marevan, Warfarin sodium), Neodicoumarin (Ethylbiscoumacetate), Acenocoumarol (Sincumar).

It should be remembered that independent initiation of use and selection of doses of Warfarin are strictly prohibited, due to the high risks of bleeding and strokes. Only a doctor who can competently assess the clinical situation and risks can prescribe anticoagulants and titrate doses.

The most popular indirect anticoagulant today is Wafarin.

Effect of the drug and indications for use

Warfarin is available under different commercial names in tablets of 2.5, 3 and 5 mg. If you start taking the tablets, they will begin to act after an hour, and the maximum therapeutic effect will appear by 5-7 days from the start of treatment. If the drug is discontinued, normal functioning of the blood coagulation system will return after 5 days. Indications for prescribing warfarin are most often all typical cases of thrombosis and thromboembolism.

Dosages

The drug is taken once a day at the same time. Start with 2 tablets per day (daily dose 5 mg). Dose adjustment is carried out on days 2-5 after monitoring coagulation parameters (INR). Maintenance dosages remain within 1-3 tablets (2.5-7.5 mg) per day. The duration of taking the drug depends on the type of pathology. Thus, for atrial fibrillation and cardiac defects, the drug is recommended for continuous use; PE requires treatment for about six months (if it occurred spontaneously or its cause was eliminated surgically) or is carried out for life (if it occurred against the background of thrombophlebitis of the veins of the legs).

Side effects

Side effects of warfarin include bleeding, nausea and vomiting, diarrhea, abdominal pain, skin reactions (urticaria, skin itching, eczema, necrosis, vasculitis, nephritis, urolithiasis, hair loss).

Contraindications

Warfarin should absolutely not be used in acute bleeding, disseminated intravascular coagulation syndrome, severe liver or kidney diseases with creatinine more than 140 µmol per liter, thrombocytopenia, in persons with a predisposition to bleeding (peptic ulcer, severe wounds, bacterial endocarditis, esophageal varices, hemorrhoids, arterial aneurysms), in the first 12 and last 4 weeks of pregnancy. Also, the drug is not recommended for impaired absorption of glucose and galactose, or for lactase deficiency. Warfarin is also not indicated for congenital deficiency of proteins S and C in the blood plasma.

Simultaneous food intake:

There is a whole list of foods that should be consumed with caution or completely excluded during warfarin treatment, as they increase bleeding and increase the risk of bleeding. These are garlic, sage and quinine contained in tonics, papaya, avocado, onions, cabbage, broccoli and Brussels sprouts, cucumber peel, lettuce and watercress, kiwi, mint, spinach, parsley, peas, soybeans, watercress, turnips , olive oil, peas, cilantro, pistachios, chicory. Alcohol also increases the risk of bleeding.

St. John's wort, on the contrary, reduces the effectiveness of the medicine and should not be used simultaneously with it.

Medicines that are contraindicated with warfarin

NSAIDs (except COX-2 inhibitors), Clopidogrel, Aspirin, Dipyridamole, penicillins in high doses, Cimetidine, Chloramphenicol.

Medicines that increase the effect of warfarin

Allopurinol, Digoxin, Amiodarone, Quinidine, Disopyramide, Disulfiram, Amitriptyline, Sertraline, Heparin, Bezafibrate, Clofibrate, Fenofibrate, Vitamins A and E, Glucagon, Glibenclamide, Gingo bilboa, Flu vaccine, Ifosfamide, Methotrexate, Etoposide, Tegafur, Zafirlu caste, Cimetidine, Indomethacin, Codeine, Metolazone, Piroxicam. Parksetine, Proguanil, Omeprazole, Simvastatin, Propafenone, Sulindac, Sulfapyrazone, Testosterone, Danazol, Tamoxifen, Fluoxetine, Troglitazone, Phenylbutazone, Flucanazole, Itraconazole, Levamisole, Miconazole, Lovastatin, Celecoxib, Cephalexin, Ciprofloxacin, Norfloxacin, Ofloxacin, Erythromy cin, Azithromycin, Tetracyclines, Cefuroxime, Clarithromycin, Chloramphenicol, Sulfamethoxazole.

What is INR and why should it be determined?

INR (International Normalized Ratio) is an indicator of blood clotting that is studied before prescribing warfarin and as a control for the effectiveness of therapy, as well as for adjusting dosages and assessing the risks of complications of treatment. This is a derivative of prothrombin time (during which the blood clots), like PTI (prothrombin index), which is normally %.

• INR is the ratio of the patient's prothrombin time to the standard prothrombin time. The higher the INR, the worse the blood clotting.
• The INR norm is 0.85-1.25. During warfarin therapy, you need to achieve an INR of 2-3

The INR is checked before starting warfarin, then on days 2-5. On average, it takes up to 10 days to select the dose of the drug and stabilize the INR within the target numbers (2-3). In the future, monitoring is carried out once every 2-4 weeks.

• If the INR is less than 2, the dose of warfarin is insufficient, it is increased by 2.5 mg (1 tablet per week), monitoring the INR every week until it reaches 2-3.
• If the INR is more than 3, then the dose of the drug is reduced (1 tablet 2.5 mg per week). INR monitoring is carried out one week after dose reduction.
• If the INR is 3.51-4.5, reduce the dose by 1 tablet. INR is monitored after 3 days.
• If the INR is 4.51-6, reduce the dose by 1 tablet with INR monitoring every other day.
• If the INR is greater than 6, warfarin is discontinued.

In general, anticoagulants are drugs with many pitfalls. The main ones are the risks of spontaneous bleeding (including hidden) and brain accidents that can lead to death. In this regard, anticoagulant drugs should be taken only as prescribed and under the supervision of a physician, taking into account all the circumstances of the disease, the risks of the patient and laboratory monitoring data, which should be thorough and regular.

New in the use of anticoagulants

Titration (gradual dose selection) of Warfarin for maintenance therapy goes through two stages: the actual dose selection and long-term treatment with maintenance doses. Today, all patients are divided into three groups depending on their sensitivity to the drug.

• Highly sensitive to Warfarin. They quickly (within a few days) from the start of taking the drug achieve therapeutic target INR values. Further attempts to increase the dose lead to a high risk of bleeding.
• Individuals with normal sensitivity achieve target INR values ​​on average after a week from the start of therapy.
• Patients with reduced sensitivity to Warfarin, even at high doses for two to three weeks, do not give an adequate INR response.

These features of the bioavailability of Warfarin in different patients may require more careful (frequent) laboratory monitoring of INR during the treatment period, linking patients to laboratories. The patient can maintain relative freedom of movement and life by purchasing a simple Coaguchek device, which works similarly to a glucometer using test strips. True, the price tag for the device itself is about rubles, and consumables (a set of test strips) will cost six to seven thousand.

Today, a new generation of anticoagulants, which successfully replace Warfarin in many situations (cardiology, prevention and treatment of deep vein thrombosis of the extremities, pulmonary embolism, in the treatment and prevention of strokes), allows us to get away from the problem of INR control.

We are talking about three main drugs: Rivaroxaban (Xarelto), Apixaban (Eliquis) and Dabigatran (Pradaxa).

The first two are now successfully replacing parenteral anticoagulants in combination with warfarin in low-risk situations of pulmonary embolism.

Rivaroxaban (tablets 10, 15, 20 mg)

It shows the lowest risk of bleeding and is safer in this group of complications compared to the combination of Warfarin and Enoxaparin. The effect of therapy appears quickly; INR monitoring is not required. In the treatment of pulmonary embolism or deep vein thrombosis of the lower extremities, 15 mg of the drug is prescribed twice a day for 3 weeks. Then they switch to a maintenance dosage of 20 mg once a day for months.

Apixaban

In the same situation, Apixaban is given in doses of 10 mg twice a day for a week, followed by 5 mg twice a day for life. The drugs are promising in terms of outpatient treatment of low-risk pulmonary embolism, which is currently treated in an inpatient setting.

These drugs are contraindicated if:

• ongoing bleeding
• in pregnant women,
• end stages of renal failure,
• severe liver pathologies.

Dabigatran

It cannot replace parenteral anticoagulants and is prescribed after treatment with them at a dose of 150 mg twice a day (110 mg twice in people over 80 years of age or receiving verapamil). In the treatment of ischemic strokes, Apixaban is the safest, which is prescribed for minor strokes on days 3-5, on average on days 6 (after a brain CT scan), and for severe strokes after 12 days.

The use of these drugs in the prevention of pulmonary embolism in patients with hip and knee replacement is also interesting. On average, anticoagulant therapy should begin 1-4 hours after surgery.

• In the case of Rivaroxaban, it is used for 35 days for hip surgery and 14 days for knee replacement.
• Dabigatran 35 and 10 days, respectively.

In cardiological practice, against the background of atrial fibrillation, stroke prevention can be carried out instead of Warfarin by any of these drugs. At the same time, Dabigatran (110 mg twice a day) and Apixaban (5 mg 2 times a day) are more effective than Warfarin and their use has a lower risk of bleeding. Both Dabigatran, Apixaban, and Rivaroxaban, compared with Warfarin in these situations, give lower statistics of complications such as hemorrhagic stroke. Rivaroxaban for the prevention of ischemic stroke due to atrial fibrillation in doses of 20 mg once a day has no advantages over Warfarin.

In the presence of mechanical prosthetic heart valves, as well as with mitral stenosis, switching from warfarin to new anticoagulants is impractical.

How to switch from one anticoagulant to another

The term new anticoagulants includes Rivoraxoban, Apixaban, Dabigatran.

• If it is necessary to switch from Warfarin to one of the new anticoagulants, Warfarin is discontinued and a period is maintained until the INR is less than 2. When this value is reached, one of the new anticoagulants is prescribed.
• If you need to replace a new anticoagulant with Warfarin, then it is simply added to the new anticoagulant until an INR of 2-3 is obtained. The INR should be monitored before the next dose of a new anticoagulant, with repeated monitoring one day after the last dose of the new anticoagulant.
• If a transition is made from parenteral forms of anticoagulants to new ones, then the first ones are immediately canceled, and a new one is given the next day.

How to compensate for incorrect reception

Often patients (especially older ones) make mistakes in the dosage regimen of the drug or simply forget whether they took it at all. In order to avoid extreme situations of bleeding or a sharp increase in the risk of thrombosis, there are certain rules for correcting errors in taking new generation anticoagulants.

• If you miss taking a pill, then under no circumstances should you take a double dose. If the drug is usually taken twice a day (Pradaxa, Eliquis), the missed tablet can be taken within 6 hours after the missed time. For Xarelto, the same can be done within 12 hours. If this is not possible, the dose should be skipped and the next one taken as planned.
• If the patient accidentally took a double dose of a twice-daily drug (Pradaxa, Eliquis), then the next scheduled dose of the drug should be skipped. If a double dose was taken for Xarelto, there is no need to skip it, take the drug as usual.
• If the patient does not remember whether he took the tablet, then for Pradaxa and Eliquis an additional dose is not required; the next dose of the drug should be only 12 hours after the previous one. For Xarelto, you should take one tablet and consume the next one after 24 hours.

Bleeding problem

As with Warfarin, bleeding of varying severity may develop with new anticoagulants. If bleeding is light, the anticoagulant will have to be discontinued. For moderate cases, additional drops of erythromass, platelet concentrate or fresh frozen plasma are added. Life-threatening bleeding requires prothrombin complex concentrate or surgical treatment.

There are no specific antidotes for warfarin (neither Vikasol nor Etamzilat are suitable).

Today, the antidote Idarucizumab is registered and used in Europe for Dabigatran. Its registration in the Russian Federation is planned for 2017. Most often, the drug is used in emergency situations (for example, in case of life-threatening bleeding or emergency surgical care).

Preoperative preparation

All major surgical interventions require transferring the patient from warfarin or new anticoagulants to parenteral low molecular weight heparins.

However, minor surgery can be provided to the patient without changing anticoagulation therapy. In particular, patients may be treated on Warfarin or new anticoagulants:

• dentists (for removal of 1-3 teeth, installation of an implant, periodontal surgery, opening of oral abscesses),
• ophthalmologists (cataract removal, glaucoma surgery).
• Diagnostic endoscopy does not require changing the anticoagulant.

The only detailed and specific article of all publications on anticoagulants, sincere thanks to everyone who worked on this material. Good health to you!

Thank you, the material was very useful.

Thank you for the detailed explanation; useful information. I’m not taking anticoagulants yet, but they’ve already been prescribed. The price is not affordable for pensioners; this is a problem.

And if I take Cardiomagnyl, can I take Xarelto? And what is the difference between them?

Add a comment Cancel reply

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In medical practice, anticoagulant therapy is intended to prevent thrombosis and treat pathologies of the heart and vascular system. Medicines are produced in the form of creams, gels, ointments, capsules, injection solutions, and tablets. It is strictly forbidden to select the dose yourself, as this can cause severe bleeding.

Impact

Thrombosis is a dangerous and common condition that often leads to heart attacks, strokes, heart attacks and death. Disability in these conditions is inevitable. Therefore, doctors prescribe anticoagulant therapy to their patients with clotting problems in advance.

Thanks to early treatment, it is possible to prevent the formation and expansion of blood clots, as well as blockage of blood vessels. Typically, anticoagulants act in a complex manner, affecting not only the blood clot itself, but also coagulation in general.

Anticoagulant therapy consists of suppressing plasma clotting factors and thrombin synthesis. It is due to thrombin that fibrin threads and thrombotic clots are formed.

Classification

Anticoagulant substances are classified into the following groups:

• pathological and physiological anticoagulants;
• indirect anticoagulants;
• direct anticoagulant components;
• new oral anticoagulants (NOACs);
• antiplatelet agents.

Modern anticoagulants, in turn, are divided into direct anticoagulants and indirect anticoagulants.

Pathological components

Formed in the blood during pathologies. These are strong immune coagulation inhibitors, which are specific antibodies that affect certain factors. As a rule, such antibodies are synthesized by the body in order to protect it from manifestations of blood clotting.

Physiological components

Normally found in the blood. They are usually distinguished into two types:

• secondary;
• primary.

This group includes the following list of substances:

• Heparin;
• Antithrombin III;
• Protein C;
• Complement inhibitor-I;
• Alpha2-macroglobulin;
• Protein S;
• Lipid and contact inhibitors;
• Antithromboplastins.

Heparin is a polysaccharide whose synthesis occurs in mast cells. Studies have shown large amounts of heparin in the liver and lungs. The use of large doses of the component suppresses platelets and leads to inhibition of blood clotting. As a result, bleeding from internal organs occurs. Therefore, it is important not to use heparin medications on your own without medical supervision.

Secondary physiological anticoagulants include the following list of drugs:

• Antithrombin I, IX;
• Antithromboplastins;
• PDF products;
• Fibrinopeptides;
• Metafactors Va, XIa.

Direct action

Direct anticoagulants reduce thrombin activity, deactivate prothrombin, inhibit thrombin and prevent the formation of new blood clots. When using direct anticoagulants, it is important to regularly monitor clotting parameters. This is necessary to prevent internal bleeding.

After using direct-acting agents, the therapeutic effect occurs immediately due to the rapid entry of substances into the body. Excretion is carried out by the kidneys.

This group of funds includes:

• Heparin - can suppress platelet aggregation, accelerating blood flow to the heart and kidneys. The drug leads to a decrease in blood pressure, a hypocholesterolemic effect, increased vascular permeability, and suppression of the proliferation of smooth muscle cells. The substance is indicated for intravenous administration in emergency conditions, as well as subcutaneously for the prevention of thrombosis. Heparin is used externally for and. The substance is included in such drugs as Heparin ointment and Hepatrombin.
• Low molecular weight heparin – has high antithrombotic activity and is bioavailable. The effect of low molecular weight heparin is long-lasting, and the risk of developing hemorrhoidal complications is low. An important difference between this group of drugs is the minimal number of side effects. The injection is carried out subcutaneously into the lateral surface of the abdomen. Low molecular weight heparins include: Fragmin, Klivarin, Clexane, Fraxiparin, Wessel Due F.
• Thrombin inhibitors. This group of medications includes: Hirudin, Girugen, Girulog, Lepirudin.

Indirect action

Indirect anticoagulants affect the biosynthesis of side enzymes of the coagulation system. However, they do not suppress the activity of thrombin, but completely destroy it. Another feature of these medications is their relaxing effect on smooth muscles. Due to this, the blood supply to the heart is stimulated.

Indirect anticoagulants are indicated for the treatment and prevention of thrombosis. Admission is carried out exclusively orally for a long time. If medications are stopped abruptly, prothrombin levels increase and the risk increases.

Indirect anticoagulants are divided into the following types:

• coumarin anticoagulants;
• Indan-1,3-dione derivatives.

Based on the classification, indirect anticoagulants, derivatives of coumarin and Indan-1,3-dione are as follows:

• Phenilin;
• Neodicoumarin;
• Warfarin;
• Acenocoumarol.

New anticoagulant substances

New anticoagulants are indicated for use in patients who need to take Varfanin for life. The fact is that Warfarin is an effective but unpredictable drug. For patients to whom it is prescribed, it is important to monitor their blood 7–10 times a day. If this is not done, the risk of bleeding increases significantly, which is ultimately difficult to stop.

The modern pharmaceutical industry is looking for ways to solve the problem of warfarin-dependent patients. For this purpose, new anticoagulants are used, which in medicine are referred to as oral anticoagulants.

Oral anticoagulants include:

• Xarelto (Rivaroxoban);
• Pradaxa (Dabegatran);
• Eliquis (Apixaban).

All these drugs are available in two dosage options. In this case, Rivaroxoban must be taken once a day. The rest are used twice a day.

Indications for the use of oral anticoagulants:

• atrial fibrillation;
• prevention of venous thrombosis;
• embolism prevention;
• ischemic stroke.

Advantages of oral anticoagulants:

• there is no need to calculate the dose;
• there is no need to regularly monitor the INR;
• Oral anticoagulant substances do not interact with food.

Flaws:

• must be taken regularly;
• a lot of research;
• risk of stomach bleeding;
• intolerance in some patients.

Indications and contraindications

Anticoagulant therapy is indicated for the following conditions:

• thrombotic and embolic stroke;
• rheumatic carditis;
• thrombophlebitis and acute thrombosis;
• the presence of atherosclerotic plaques;
• varicose veins and;
• aortic aneurysm;
• ischemic disease;
• TELA;
• DIC syndrome;
• atrial fibrillation.

It is important to note that not everyone is allowed to use anticoagulant drugs. Substances often prohibited from taking:

• patients suffering from bleeding hemorrhoids;
• patients with gastric and duodenal ulcers;
• persons suffering from renal or liver failure;
• with cavernous tuberculosis;
• patients suffering from vitamin C and K deficiency;
• patients with pancreatitis;
• persons suffering from an acute form of leukemia;
• with alcoholism;
• patients suffering from Crohn's disease;
• with hemorrhagic retinopathy.

It is important to note that anticoagulants should not be used during menstruation, while pregnant or while breastfeeding. It is also prohibited for older people to take substances after childbirth.

Side effects

The phenomena identified in the reference books include the following list:

• nausea;
• vomit;
• skin rashes;
• osteoporosis;
• alopecia;
• possible complications in the form of bleeding from internal organs.

Antiplatelet agents

Prevent platelet aggregation and enhance the effectiveness of anticoagulants. Antiplatelet agents are able to dilate blood vessels and have an antispasmodic effect.

Antiplatelet agents include:

• Aspirin;
• Ticlopidine;
• Tirofiban;
• Dipyridamole.

Aspirin, or Acetyl salicylic acid, is a bright representative of the group. The drug is available in various dosage forms. The substance is included in many products. Aspirin can inhibit platelet aggregation, provoke vasodilation and prevent the early formation of blood clots. Previously, Aspirin was widely used to reduce body temperature, but now the medicine is highly discouraged for this.

Anticoagulant substances are effective; they cannot be avoided in the treatment of pathologies of the cardiovascular system. However, it is important not to take them on your own, even the usual Aspirin. People who are used to “prescribing medications” to themselves often suffer from many side effects. It must be remembered that self-medication with anticoagulants can lead to irreversible and serious consequences in the form of severe bleeding.

Useful video about anticoagulants

Today, many drugs are known that increase blood clotting. Such agents are usually called coagulants. They most often have only a positive effect on the body as a whole. With their help you can stop even severe bleeding. Drugs that increase blood clotting are also called hemostatics. They can act on the body both directly and indirectly. However, their activity may also vary.

Direct coagulants are capable of incorporating biological components of the entire blood coagulation system. However, such drugs can only be used topically. Some medications can only be introduced into the body through injections.

• recent myocardial infarction;
• previously noticed increased rate of blood clotting;
• the body's predisposition to the formation of blood clots.

Indirect coagulants necessarily contain vitamin K. They also exhibit good hormonal properties. Such medications are used either orally or by injection.

A drug such as Thrombin is most often used to increase blood clotting.

This medicine is produced in the form of a powder placed in ampoules. In most cases, it is used only topically. They are classified as direct-acting coagulants.

To use Thrombin and truly improve clotting, it must be properly diluted. To do this, the powder is poured into saline solution. As a result, the ampoule will contain a mixture consisting of prothrombin, calcium and thromboplastin.

Locally, this drug is used in cases of minor bleeding from small vessels, as well as hemorrhages from parenchymal organs, which do not pose a threat to human life. Quite often it is used for traumatic injuries during operations on certain organs.

In dentistry, Thrombin is also used topically for severe bleeding from the gums. To do this, use a hemostatic sponge, which is pre-impregnated with Thrombin.

However, there are also cases when Thrombin needs to be used internally. Most often this is in demand in pediatrics. To do this, the powder must be dissolved in sodium chloride or in a special drug “Amben”. This solution is prescribed for severe intragastric bleeding. When bleeding occurs in the respiratory tract, Thrombin is administered by inhalation.

To increase blood clotting, many doctors also prescribe a medication such as Fibrinogen. It is produced in the form of special bottles in the form of a porous mass.

Fibrinogen has a systemic effect on the entire body.

Sometimes it is obtained from blood plasma from a donor. Quite often it happens that the active component of this medicine can turn into fibrins, which increases the risk of blood clots.

1. Fibrinogen is used mainly for emergency therapy.
2. With heavy bleeding, the highest activity in the body of this drug is observed.
3. Fibrinogen is especially important in gynecology in case of bleeding due to placental abruption, when a woman needs to save not only her life, but also try to save the child.

Most often, this drug is prescribed in the form of droppers.

There are also cases of its use for severe bleeding of internal organs, when a fibrin film is applied to the bleeding area. In order to begin introducing the drug into the body, it must first be dissolved in water. Fibrinogen is administered only intravenously or intravenously, but always very slowly.

Vikasol and Phytomenadione

Vikasol is a coagulant that can be bought at almost any pharmacy. It is usually sold in the form of an injection solution or tablets. Vikasol belongs to indirect coagulants. It is of synthetic origin and is considered an analogue of vitamin K. It is dissolved in water. This drug is used to accelerate the formation of fibrin blood clots.

Vikasol itself has virtually no effect. The effects on the body are caused by the vitamins that are synthesized from it, especially vitamin K. Therefore, the results after taking such a medicine will be noticeable no earlier than 12 hours. However, with intravenous administration, the result can be seen within half an hour.

Most often, Vikasol is prescribed in case of a lack of vitamin K in the body or when the prothrombin index is low.

• long-term use of vitamin K antagonists;
• use of sulfa drugs;
• long-term therapy with broad-spectrum antibiotics;
• preventive measures taken to eliminate hemorrhagic pathology in infants;
• presence of cystic fibrosis;
• frequent diarrhea in children;
• pregnancy complicated by certain systemic diseases;
• hepatitis affecting clotting;
• severe bleeding;
• preparatory stage before operations.

But you need to remember that along with Vikasol, its antagonists can also be prescribed. In this case, the effect of the drug is significantly reduced.

Phytomenadione is also used to increase blood clotting.

It can be administered intravenously. The ampoule contains 1 ml of this medicine. This product can also be used in tablet form. The product is of synthetic origin.

• long-term use of anticoagulants;
• sulfonamide therapy;
• ulcerative colitis;
• antibiotic therapy;
• hemorrhagic syndrome;
• preparation for heavy surgical operations.

Quite often, fibrinolysis inhibitors are prescribed to increase blood clotting. Aminocaproic acid can be classified as a remedy that improves this indicator. It is considered a drug of synthetic origin. Usually available in powder form. When using such a drug, you can slow down the process of converting plasminogen to plasmin. This is why fibrin blood clots persist for a longer time.

This drug also has a good anti-shock effect. Its toxicity is low. It is quickly excreted from the body along with urine.

1. Aminocaproic acid is introduced into the body during massive blood transfusions, when it is necessary to increase blood clotting.
2. It is almost always prescribed intravenously.
3. It is also used to prevent allergic reactions, but there is a possibility of developing a number of side effects.

A drug such as Ambien has a good effect on blood clotting. This is a synthetic agent that has an antifibrinolytic effect.

However, you should always remember that the best remedy that will affect the increase in blood clotting is prescribed only by a doctor. In this case, self-medication is strictly prohibited, since bleeding can be life-threatening.

Therefore, if you notice symptoms of bleeding, especially from internal organs, you should immediately seek help from a specialist. Only a doctor will be able to determine the cause affecting the bleeding and prescribe the most effective drugs that increase blood clotting to improve the condition in each individual case.

The liquid state of the blood and the integrity of the bloodstream are necessary conditions for the life of the body. These conditions are created by the blood coagulation system, which keeps circulating blood in a liquid state.

The blood coagulation system is part of a larger system - the system for regulating the aggregate state of blood and colloids (RAS system), which maintains the aggregate state of the internal environment of the body at a level that is necessary for normal life. The RASK system ensures the maintenance of the liquid state of the blood and restoration of the properties of the walls of blood vessels, which change even during their normal functioning. Thus, the body has a special biological system that ensures, on the one hand, the preservation of the liquid state of the blood, and on the other, the prevention and stopping of bleeding by maintaining the structural integrity of the walls of blood vessels and the rapid thrombosis of the latter in case of damage. This system is called the hemostasis system.

There are vascular-platelet hemostasis, which ensures the cessation of bleeding from microcirculatory vessels through the formation of platelet thrombi (primary hemostasis), as well as coagulation enzymatic hemostasis, which ensures the cessation of bleeding through the formation of a fibrin thrombus (stopping bleeding in large vessels).

The fluid state of the blood is ensured by the anticoagulant system. The trigger for blood clotting is damage to blood vessels. Coagulation enzymatic hemostasis occurs in three phases:

PHASE I Formation of prothrombinase (triggered by tissue

high thromboplastin with subsequent formation

I eat blood (platelet and erythrocyte)

prothrombinase).

PHASE II The appearance of prothrombinase means the beginning of second

swarm of blood coagulation phase - formation

thrombin (the process occurs instantly - 2-5 sec

PHASE III Under the influence of thrombin in the third phase

fibrinogen is converted into fibrin. About

fibrin formation and completes the formation

blood clot.

The aggregate (liquid) state of blood is ensured by the dynamic balance of the potentials of the coagulation and anticoagulation systems. The liquid state of the blood is primarily maintained by the natural anticoagulants present in it.

gulants (anti-coagulant system). First of all, this is a group of antithromboplastins that inhibit the action of prothrombinase (antithrombin III, alpha-2-macroglobulin, or antithrombin IV). In addition, heparin is produced by mast cells and basophils.

There is a third component - the fibrinolysis system, which begins to act simultaneously with clot retraction.

Fibrinolysis is the process of breakdown of fibrin, which forms the basis of a blood clot. The main function of fibrinolysis is to restore the lumen (recanalization) of a vessel clogged with a clot.

The breakdown of fibrin is carried out by the proteolytic enzyme plasmin, which is found in the plasma in the form of plasminogen.

The pathology of blood clotting in the clinic manifests itself either in the form of hemorrhages or in the form of increased thrombus formation, a combination of both phenomena is also possible (in DIC syndrome - dissociated intravascular coagulation).

In the process of treating patients with these conditions, two main groups of drugs are used:

1. Medicines that promote clotting

blood, which means stopping bleeding (hemostasis)

2. Drugs that reduce blood clotting (antithrom

botic) or drugs for thrombosis and for their

prevention.

Each of these groups is divided into subgroups that have different effects on thrombus formation, the activity of the fibrinolytic system, platelet aggregation and the vascular wall.

I. HEMOSTATICS

1. Coagulants (agents that stimulate the formation

fibrin thrombi):

a) direct action (thrombin, fibrinogen);

b) indirect action (vicasol, phytomenadione).

2. Fibrinolysis inhibitors:

a) synthetic origin (aminocaprono

va and tranexamic acids,

b) animal origin (aprotinin, contri

feces, pantripin, gordox "Gideon"

Richter", Hungary);

3. Stimulators of platelet aggregation (serotonin

adipate, calcium chloride).

4. Agents that reduce vascular permeability:

a) synthetic (adroxon, etamsylate, iprazox

b) vitamin preparations (ascorbic acid,

rutin, quercetin).

c) herbal preparations (crappie

you, yarrow, viburnum, water pepper,

arnica, etc.)

II. ANTI-CLOTTING DRUGS, OR ANTI-CLOTTING DRUGS

TITHROMBOTIC DRUGS:

1. Anticoagulants:

a) direct action (heparin and its preparations,

hirudin, sodium citrate, antithrombin III);

b) indirect action (neodicoumarin, syncumar,

phenyline, fepromarone).

2. Fibrinolytics:

a) direct action (fibrinolysin or plasmin);

b) indirect (plasminogen activators) action

(streptolyase, streptokinase, urokinase, ac

3. Antiplatelet agents:

a) platelet (acetylsalicylic acid,

dipyridamole, pentoxifylline, ticlopidine,

indobufen);

b) erythrocyte (pentoxifylline, reopoliglu

kin, reogluman, rondex).

DRUGS THAT INCREASE BLOOD CLOTTING (HEMOSTATICS)

COAGULANTS

According to the classification, this group of drugs is divided into direct and indirect coagulants, but sometimes they are divided according to another principle:

1) for local use (thrombin, hemostatic sponge

chelic, fibrin film, etc.)

2) for systemic use (fibrinogen, Vicasol).

TROMBIN (Trombinum; dry powder in amp. 0.1, which corresponds to 125 units of activity; in bottles of 10 ml) is a direct-acting coagulant for topical use. Being a natural component of the blood coagulation system, it causes an effect in vitro and in vivo.

Before use, the powder is dissolved in saline solution. Typically, the powder in the ampoule is a mixture of thromboplastin, calcium and prothrombin.

Apply only locally. Prescribed to patients with bleeding from small vessels and parenchymal organs (surgeries on the liver, kidneys, lungs, brain), bleeding from the gums. Used locally in the form of a hemostatic sponge impregnated with thrombin solution, hemastatic sponge

Lagenova, or simply applying a tampon soaked in thrombin solution.

Sometimes, especially in pediatrics, thrombin is used orally (the contents of the ampoule are dissolved in 50 ml of sodium chloride or 50 ml of a 5% Ambien solution, administered 1 tablespoon 2-3 times a day) for gastric bleeding or by inhalation for bleeding from the respiratory tract.

FIBRINOGEN (Fibrinogenum; in bottles of 1.0 and 2.0 dry porous mass) - used for systemic effects. It is also obtained from donor blood plasma. Under the influence of thrombin, fibrinogen is converted into fibrin, which forms blood clots.

Fibrinogen is used as an emergency medicine. It is especially effective when there is a deficiency in cases of massive bleeding (placental abruption, hypo and afibrinogenemia, in surgical, obstetric, gynecological and oncological practice).

It is usually prescribed into a vein, sometimes locally in the form of a film applied to the bleeding surface.

Before use, the drug is dissolved in 250 or 500 ml of warmed water for injection. It is administered intravenously by drip or slow stream.

VICASOL (Vicasolum; in tablets, 0.015 and in amps, 1 ml of 1% solution) is an indirect coagulant, a synthetic water-soluble analogue of vitamin K, which activates the formation of fibrin clots. Referred to as vitamin K3. The pharmacological effect is not caused by Vikasol itself, but by the vitamins K1 and K2 formed from it, so the effect develops after 12-24 hours, with intravenous administration - after 30 minutes, with intramuscular administration - after 2-3 hours.

These vitamins are necessary for the synthesis in the liver of prothrombin (factor II), proconvertin (factor VII), as well as factors IX and X.

Indications for use: with an excessive decrease in the prothrombin index, with severe vitamin K deficiency caused by:

1) bleeding from parenchymal organs;

2) the procedure of exchange blood transfusion, if

they poured canned blood onto (the child);

and also when:

3) long-term use of vitamin K antagonists -

aspirin and NSAIDs (impairing platelet aggregation

4) long-term use of broad-spectrum antibiotics

action (chloramphenicol, ampicillin, tetracycline

lin, aminoglycosides, fluoroquinolones);

5) use of sulfonamides;

6) prevention of hemorrhagic disease of newborns;

7) prolonged diarrhea in children;

8) cystic fibrosis;

9) in pregnant women, especially those suffering from tuberculosis

lesis and epilepsy and receiving appropriate treatment

10) overdose of indirect anticoagulants;

11) jaundice, hepatitis, as well as after injuries, blood

diseases (hemorrhoids, ulcers, radiation sickness);

12) preparation for surgery and post-operation

tion period.

The effects can be weakened by simultaneous administration of vikasol antagonists: aspirin, NSAIDs, PAS, indirect anticoagulants of the neodicoumarin group.

Side effects: hemolysis of red blood cells when administered intravenously.

PHYTOMENADIONE (Phytomenadinum; 1 ml for intravenous administration, as well as capsules containing 0.1 ml of a 10% oil solution, which corresponds to 0.01 of the drug). Unlike natural vitamin K1 (trans-compounds), it is a synthetic preparation. It is a racemic form (a mixture of trans- and cis-isomers), and in terms of biological activity it retains all the properties of vitamin K1. It is quickly absorbed and maintains peak concentration for up to eight hours.

Indications for use: hemorrhagic syndrome with hypoprothrombinemia caused by decreased liver function (hepatitis, cirrhosis), ulcerative colitis, overdose of anticoagulants, long-term use of high doses of broad-spectrum antibiotics and sulfonamides; before major operations to reduce bleeding.

Side effects: hypercoagulation phenomena if the dosage regimen is not followed.

Among the drugs related to direct-acting coagulants, the clinic also uses the following drugs:

1) prothrombin complex (VI, VII, IX, X factors);

2) antihemophilic globulin (factor VIII).

FIBRINOLYSIS INHIBITORS (ANTIFIBRINOLYTICS)

AMINOCAPRONIC ACID (ACA) is a powdered synthetic drug that inhibits the conversion of profibrinolysin (plasminogen) into fibrinolysin (plasmin) by acting on the profibrinolysin activator and thereby contributes to the preservation of fibrin clots.

In addition, ACC is also an inhibitor of kinins and some factors of the compliment system.

It has anti-shock activity (inhibits proteolytic enzymes and also stimulates the neutralizing function of the liver).

The drug is low-toxic and is quickly eliminated from the body

with urine (after 4 hours).

Used in emergency clinics, during surgical interventions and in various pathological conditions when the fibrinolytic activity of blood and tissues is increased:

1) during and after operations on the lungs, prostate, pancreas

breast and thyroid glands;

2) with premature placental abruption, long-term

retention of a dead fetus in the uterus;

3) for hepatitis, cirrhosis of the liver, for portal hypertension

hypertension, when using the device artificially

low blood circulation;

4) at stages II and III of DIC syndrome, with ulcerative,

nosebleeds, pulmonary bleeding.

ACC is administered during massive transfusions of canned blood, administered intravenously or orally.

Available: powder and bottles of 100 ml of sterile 5% solution in isotonic sodium chloride solution. IN

Due to the fact that ACC has anti-shock activity, inhibits proteolytic enzymes and kinins, inhibits the formation of antibodies, the drug is used for shock reactions and as an antiallergic agent.

Side effects: possible dizziness, nausea, diarrhea, mild catarrh of the upper respiratory tract.

AMBEN (Ambenum, aminomethylbenzoic acid) is also a synthetic drug, similar in chemical structure to para-aminobenzoic acid. White powder, poorly soluble in water. It is an antifibrinolytic agent. Ambien inhibits fibrinolysis, its mechanism of action is similar to ACC.

Indications for use are the same. Prescribed intravenously, intramuscularly and orally. When administered into a vein, it acts quickly, but only for a short time (3 hours). Release form: ampoules of 5 ml of 1% solution, tablets of 0.25.

Sometimes anti-enzyme drugs are indicated, in particular, kontrikal. It inhibits plasmin, collagenase, trypsin, chymotrypsin, which play an important role in the development of many pathophysiological processes. Drugs in this group have an inhibitory effect on the catalytic interaction of individual fibrinolysis factors and blood coagulation processes.

Indications for use: local hyperfibrinolysis - postoperative and post-portal bleeding; hypermenorrhea; generalized primary and secondary hyperfibrinolysis in obstetrics and surgery; initial stage of DIC syndrome, etc.

Side effects: rarely allergies; embryotoxic effect; With rapid administration - malaise, nausea.

DRUGS THAT INCREASE PLATELET AGGREGATION AND ADHESION

SEROTONIN. Its use is associated with stimulation of platelet aggregation, tissue swelling, and changes in microcirculation, which contributes to the formation of platelet thrombi. Serotonin in the form of adipate (Serotonini adipinatis in ampoules of 1 ml of 1% solution) is used intravenously or intramuscularly for hemorrhages associated with pathology of blood platelets (thrombocytopenia, thrombocytopathy). At the same time, the number of platelets increases, the bleeding time is shortened, and the resistance of capillaries increases.

Used for type I von Willebrandt disease, hypo- and aplastic anemia, Werlhoff disease, hemorrhagic vasculitis.

It should not be used in case of kidney pathology, in patients with bronchial asthma, or in cases of blood hypercoagulation.

Side effect: with rapid administration - pain along the vein; pain in the abdomen, in the heart area, increased blood pressure, heaviness in the head, nausea, diarrhea, decreased diuresis.

CALCIUM PREPARATIONS

CALCIUM is directly involved in platelet aggregation and adhesion, and also promotes the formation of thrombin and fibrin. Thus, it stimulates the formation of both platelet and fibrin blood clots.

Indications for use:

1) as a means of reducing vascular permeability,

with hemorrhagic vasculitis;

2) as a hemostatic agent for pulmonary,

stomach, nose, uterine bleeding, and

also before surgery;

3) for bleeding associated with a decrease in calcium

in blood plasma (after transfusion of large coli

quality of citrated blood, plasma substitutes).

Use calcium chloride (intravenously and orally).

Side effects: with rapid administration, cardiac arrest and decreased blood pressure are possible; with intravenous administration, a feeling of heat is noted ("hot prick"); with subcutaneous administration of calcium chloride - tissue necrosis.

DRUGS THAT REDUCE VASCULAR WALL PERMEABILITY

SYNTHETIC PREPARATIONS

ADROXONE (Adroxonum; in amp. 1 ml 0.025%) is a preparation of adrenochrome, a metabolite of adrenaline. It does not increase blood pressure, does not affect the activity of the heart and blood clotting.

Its main effect is to increase the density of the vascular wall and activate platelet aggregation and adhesion. Therefore, adroxon has a hemostatic effect during capillary bleeding, when the permeability of the walls of these vessels is especially increased. However, in case of massive bleeding, the drug is not effective.

Indications for use:

1) with parenchymal and capillary bleeding;

2) for injuries and operations;

3) with intestinal bleeding in newborns;

4) with melena;

5) with platelet purpura.

Adroxon is used topically (tampons, wipes), intramuscularly or subcutaneously. ETHAMSYLAT or dicinone (Ethamsylatum; in tablets of 0.25 and in amps of 2 ml of 12.5% ​​solution) is a synthetic derivative of dioxybenzene. The drug reduces vascular permeability, reduces transudation and exudation of the liquid part of the plasma, normalizes the permeability of the vascular wall and improves microcirculation, increases blood clotting as it promotes the formation of thromboplastin (hemostatic effect). The latter effect develops quickly - with intravenous administration after 5-15 minutes, the most pronounced - after 1-2 hours. In tablets, the effect appears after 3 hours. The drug is administered into a vein, subcutaneously or intramuscularly.

Indications for use:

1) platelet purpura;

2) intestinal and pulmonary bleeding (surgery);

3) hemorrhagic diathesis;

4) operations on ENT organs;

5) diabetic angiopathy (ophthalmology).

Side effects - sometimes there is heartburn, a feeling of heaviness in the epigastric region, headache, dizziness, facial flushing, parasthesia of the legs, decreased blood pressure.

VITAMINS PREPARATIONS

To eliminate increased vascular permeability, especially in the presence of hemorrhages, vitamin C preparations (ascorbic acid), as well as various flavonoids (rutin, ascorutin, quercetin, vitamin P), as well as vitamers, that is, semisynthetic derivatives - venoruton and troxevasin in various medicinal products, are used forms (capsules, gel, solutions). Vitamin P preparations are used for intensive transudation of the liquid part of the plasma, for example, for swelling of the legs (thrombophlebitis). In addition, these drugs are prescribed for hemorrhagic diathesis, hemorrhages in the retina, radiation sickness, arachnoiditis, hypertension and overdose of salicylates. Rutin and ascorutin are used in pediatrics to eliminate intense trance

dation in children suffering from scarlet fever, measles, diphtheria and toxic flu.

RUTIN is available in tablets of 0.02 (2-3 times per

day). ASKORUTIN - 0.05 each. VENORUTON - in capsules of

0, 3; ampoules of 5 ml of 10% solution. Preparations from plants (infusions, extracts, tablets) have a weak hemostatic effect. Therefore, they are used for light bleeding (nasal, hemorrhoidal), for bleeding, hemoptysis, hemorrhagic diathesis, in obstetric and gynecological practice.

ANTI-COLOTTING MEDICINES (ANTITIS)

RHOMBOTIC DRUGS)

ANTICOAGULANTS

1. Anticoagulants (drugs that interfere with the formation of

fibrin thrombi):

a) direct anticoagulants (heparin and its preparations,

hirudin, sodium hydrogen citrate, antit concentrate

rhombin III) - cause an effect in vitro and in

b) indirect anticoagulants (derivatives

oxycoumarin: neodicoumarin, syncumar, pelentan

and etc.; indandione derivatives - phenyline, etc.)

Cause effect only in vivo.

HEPARIN (Heparinum; 5 ml bottle containing 5000, 10000 and 20000 IU per 1 ml, Gedeon Richter, Hungary) is a natural anticoagulant factor produced by mast cells. Heparin is a collective name for a group of linear anionic polyelectrolytes that differ in the number of sulfuric acid residues. There are high and low molecular weight heparins (average molecular weight -

Heparin is a new galenic drug obtained from the lungs and liver of cattle. It is the strongest organic acid due to its sulfuric acid residues and the presence of carboxyl groups, which gives it a very strong negative charge. Therefore, it, in fact, belongs to anionic polyelectrolytes. Due to its negative charge, in the blood heparin combines with positively charged complexes and is sorbed on the surface of the membranes of endothelial cells and macrophages, thereby limiting the aggregation and adhesion of platelets. The effect of heparin largely depends on the plasma concentration of antithrombin III.

Pharmacological effects of heparin:

1) heparin has an anticoagulant effect, so

how it activates antithrombin III and irreversibly

does not disappear IXa, Xa, XIa and XIIa coagulation factors

2) moderately reduces platelet aggregation;

3) heparin reduces blood viscosity, reduces permeability

blood vessels, which facilitates and accelerates blood flow

vi, prevents the development of stasis (one of the fact

dits that promote thrombus formation);

4) reduces the content of sugar, lipids and chylomicrons

in the blood, has an antisclerotic effect,

connects some components of a compliment,

the synthesis of immunoglobulins, ACTH, aldosterone melts,

and also binds histamine, serotonin, showing

thereby, antiallergic effect;

5) heparin is potassium-sparing and anti-inflammatory

telny, analgesic effects. Besides,

heparin increases diuresis and reduces

vascular resistance due to expansion of re

positive vessels, eliminates spasm of coronary arteries

Indications for use:

1) for acute thrombosis, thromboembolism (acute in

myocardial infarction, thrombosis of the pulmonary artery, renal

veins, ileocecal vessels), thromboembolism in the

2) when working with artificial blood circulation devices

breastfeeding, artificial kidney and heart;

3) in laboratory practice;

4) for burns and frostbite (improving microcirculation

5) in the treatment of patients in the initial stages of DIC syndrome

Roma (with fulminant purpura, severe gastrointestinal

6) in the treatment of patients with bronchial asthma, rheumatism

mom, as well as in complex therapy of patients with glome

roll nephritis;

7) when performing extracorporeal hemodialysis,

hemosorption and forced diuresis;

8) with hyperaldosteronism;

9) as an antiallergic agent (bronchial

10) in a complex of therapeutic measures for patients with ate

rosclerosis.

Side effects:

1) development of hemorrhages, thrombocytopenia (30%);

2) dizziness, nausea, vomiting, anorexia, diarrhea;

3) allergic reactions, hyperthermia.

To eliminate complications (hemorrhages), heparin antidotes (protamine sulfate in the form of a 5% solution) are injected into the vein

or POLYBREN; 1 mg of protamine sulfate neutralizes 85 units of heparin; inject slowly).

At one time, on average, 10,000 units are administered intravenously to a patient with acute thrombosis. Per day up to 40,000 - 50,000 units intravenously, administered slowly. Can be administered intramuscularly and subcutaneously (in the area of ​​least vascularization). In recent years, to prevent thrombosis, it has been recommended to administer 5000 units of heparin subcutaneously or intradermally every 6-8 hours. Heparin ointment is also available in tubes of 25.0 (2500 units). Inhalation in the form of an aerosol, as an antiallergic agent, the drug is administered using an ultrasonic inhaler at 500 units/kg per day. Inhalations are carried out 2-3 times a week. A single dose is diluted in distilled water in a ratio of 1:4.

HIRUDIN and its preparations (hirudont, etc.) is a product of leeches. The anticoagulant and anti-inflammatory effects of these drugs are used. Prescribed topically (ointments and gels) for superficial inflammation of the veins, vein thrombosis, trophic ulcers of the leg, furunculosis, inflammation of the lymph nodes, to improve the healing of sutures after injuries and burns.

Side effect - allergic reactions (rash, itching, Quincke's edema).

SODIUM HYDROCITRATE is used only for blood preservation. The citric acid anion combines with the calcium ion, which binds the activity of the latter. The substance is added in excess. The patient should not use it, since sodium hydrogen citrate will block calcium ions and the patient will develop arrhythmia, possibly developing heart failure and cardiac arrest.

Sometimes prescribed orally to eliminate hypercalcemia and treat poisoning with cardiac glycosides.

If a patient is transfused with up to 500 ml of canned blood, this does not require any additional measures. If blood is transfused in a volume of more than 500 ml, then for every 50 ml in excess of 500 ml of the volume of transfused blood, add 5 ml of a 10% calcium chloride solution.

INDIRECT ACTION ANTICOAGULANTS (PERO

RAL ANTICOAGULANTS)

Of the large number of anticoagulants, the most common are drugs of the coumarin group. There are many drugs, but the most commonly used are neodicoumarin (pelentan), syncumar, fepromarone, phenylin, amefine, and farfavin.

NEODICUMARIN (Neodicumarinum; in tablets 0.05 and 0.1), syncumar, dicoumarin, fepromarone, omefin, phenyline - phenylindandione derivatives, very similar in pharmacodynamics. Their mechanism of action is due to the fact that they are antivitamins K, that is, they act as vitamin K antagonists.

By suppressing its activity, these drugs inhibit the synthesis of proconvertin (factor VII), prothrombin (factor II), as well as blood clotting factors IX and X, which are necessary for coagulation homeostasis, that is, for the formation of fibrin clots. These drugs do not act immediately, but after 8-24 hours, that is, they are slow-acting agents with cumulative properties. Moreover, different drugs in this group have different speeds and strengths of action, and different degrees of accumulation. Another feature of their action is their long duration of action.

These drugs are used only orally, as they are well absorbed, then they are brought back to the intestine through the bloodstream, released into its lumen and absorbed again (recirculation). All drugs form a weak bond with plasma proteins and are easily displaced from it by other drugs. Act only in vivo.

Indications for use:

1) to reduce blood clotting for professional purposes

lactation and treatment of thrombosis, thrombophlebitis and

thromboembolism (myocardial infarction), embolic

strokes;

2) in surgery to prevent thrombosis in

postoperative period.

Side effects are rarely recorded in the form of dyspeptic syndrome (nausea, vomiting, diarrhea, loss of appetite). During pharmacotherapy with drugs such as neodicoumarin, complications occur in the form of bleeding due to overdose, with the correct dose, but without taking into account drug interactions. For example, with the simultaneous administration of neodicoumarin and butadione or salicylates. In this case, bleeding is also possible through an intact vessel wall, for example, in patients with peptic ulcer disease. Treatment should be carried out under constant monitoring of the level of prothrombin in the blood. For bleeding, a solution of vikasol, vitamin P, rutin, calcium chloride is administered, and 70-100 ml of donor blood is transfused.

Treatment with anticoagulants is a difficult task for the doctor. It is necessary to monitor the prothrombin index, which should be 40-50. Treatment is strictly individual.

There are a number of contraindications to the use of this group of drugs:

1) open wounds, stomach ulcers;

2) endocarditis;

3) hepatitis, liver cirrhosis;

4) threatened abortion;

5) kidney disease.

FIBRINOLYTICS (THROMBOLYTICS)

1. Direct action - fibrinolysin (plasmin).

2. Indirect action (plasminogen activators: acti

lyse, streptokinase, streptodecase, urokinase).

FIBRINOLYSIN (available in powder form in bottles containing 10, 20, 30 and 40 thousand units) is an old drug that is a fibrinolytic. It is obtained from donor blood plasma. As a proteolytic enzyme, it breaks down fibrin, acting on the surface of the blood clot. It eliminates only fibrin thrombi during the first days of their formation, dissolves only fresh fibrin threads in the veins, leading to recanalization of blood vessels.

Fibrin degradation products have anticoagulant properties because they inhibit the polymerization of fibrin monomers and the formation of thromboplastin.

Fibrinolysin is an emergency drug prescribed for thromboembolic conditions:

Peripheral vascular occlusion;

Thrombosis of blood vessels in the brain, eyes;

IHD (myocardial infarction);

When removing a blood clot from a vascular shunt.

This drug has significant disadvantages: - it is very expensive (it is made from donor blood); - not very active, does not penetrate well into the blood clot. Side effects from the administration of fibrinolysin, a foreign protein, can occur in the form of allergic reactions, as well as nonspecific reactions to the protein (facial hyperemia, pain along the vein, as well as behind the sternum and in the abdomen) or in the form of fever, urticaria.

Before use, the drug is dissolved in an isotonic solution at the rate of 100-160 units of fibrinolysin per 1 ml of solvent. The prepared solution is poured intravenously (10-15 drops per minute).

INDIRECT ACTION FIBRINOLYTICS

STREPTOKINASE (streptase, avelysin; available in amps containing 250,000 and 500,000 units of the drug) is a more modern drug, an indirect fibrinolytic. It is obtained from beta-hemolytic streptococcus. This is a more active and cheaper drug. It stimulates the transition of the proactivator to the activator, transforming profibrinolysin into fibrinolysin (plasmin). The drug is able to penetrate inside the blood clot (activating fibrinolysis in it), which distinguishes it favorably from fibrinolysin. Streptokinase is most effective when

action on a blood clot that formed no more than seven days ago. At the same time, this fibrinolytic is able to restore the patency of blood vessels and the breakdown of blood clots.

Indications for use:

1) in the treatment of patients with superficial and deep

thrombophlebitis;

2) with thromboembolism of the pulmonary vessels and ophthalmic vessels

3) with septic thrombosis;

4) with fresh (acute) myocardial infarction. Side effects

effects: 1) allergic reactions (antibodies to strep

tokokkam); 2) hemorrhages; 3) drop in hemoglobin level

bina, red blood cell hemolysis

(direct toxic effect);

4) vasopathy (formation of CEC).

In our country, based on streptokinase, STREPTODECASE was synthesized, a similar drug with a longer-lasting effect. Allergic reactions to this drug are also possible.

UROKINASE is a drug synthesized from urine. It is considered a more modern remedy and produces less allergic reactions than streptokinase.

General note: when a large amount of fibrinolytics is used in the body, blood clotting processes develop compensatoryly. Therefore, all these drugs must be administered together with heparin. In addition, using this group of drugs, fibrinogen levels and thrombin time are constantly monitored.

MEDICINES INTERPEDING PLATELET AGGREGATION

(ANTIAGREGANTS)

Antiplatelet agents - a group of anticoagulants:

1. Platelet (acetylsalicylic acid (ASA),

heparin, dipyridamole, ticlopidine, indobufen, pen

toxifylline).

2. Erythrocyte (pentoxifylline, rheopolyglucin).

ACETYLSALICYLIC ACID (Acidum acetylsalicylicum; in tablets of 0.25) is a vitamin K antagonist and can irreversibly block platelet cyclooxygenase. Due to this, the formation of arachidonic acid metabolites, in particular, aggregating prostaglandins and thromboxane A, which is the most powerful endogenous aggregant and vasoconstrictor, quickly decreases in them.

In addition to inhibiting platelet adhesion, ASA, being a vitamin K antagonist, in large doses disrupts the formation of fibrin clots.

It is necessary to note a number of very important points for the clinic:

1. Prevention of platelet aggregation by ASA when using very small doses. The optimal dose for this effect is from 20 to 40 mg per day. Taking 30-40 mg of aspirin blocks platelet aggregation for 96 hours. A dose of 180 mg per day irreversibly inhibits the enzyme cyclooxygenase (COX). Large doses, equal to 1000 - 1500 mg of ASA per day, can suppress COX in the vascular wall, where the formation of another prostaglandin - prostacyclin J2. The latter prevents platelet aggregation and adhesion, and also causes vasodilation.

Thus, large doses of ASA cause inhibition of COX both in platelets (which is desirable) and in the vascular wall (which is undesirable). The latter can provoke thrombus formation.

2. ASA as an NSAID acts for several hours after administration. At the same time, the antiaggregation effect lasts as long as platelets live, that is, 7 days, since inhibition of COX in them is an irreversible phenomenon; the enzyme is not synthesized by the plate again. After about a week, a new platelet population is restored with an adequate supply of COX.

Taking these facts into account, one can understand why, when taking small doses of ASA, coagulation is reduced and bleeding does not occur.

Indications for the use of ASA (as an antiplatelet agent):

1) prevention of the occurrence of arterial blood clots;

2) with angina pectoris;

3) for hypertension;

4) with atherosclerosis.

As an antiplatelet drug, the drug is prescribed according to the following scheme: the first day 0.5 2 times, then 0.25 per day for several months and sometimes years. To reduce the risk of ulcerogenesis, MIKRISTIN was released - a granular microcrystalline preparation of ASA, enclosed in a polyvinyl acetate shell.

For similar indications, indobufen and indomethacin are also prescribed.

DIPIRIDAMOLE (Dypiridomalum; synonyms: chimes, persantyl; in tablets or tablets of 0.025 and 0.075, as well as in amps of 2 ml of 0.5% solution) - an antianginal agent. Competitive inhibitor of phosphodiesterase and adenosine deaminase. Dipyridamole prevents platelet aggregation by limiting aggregating factors in them (cAMP accumulates in platelets) and potentiating the action of adenosine. The latter promotes vasodilating and antiaggregation effects and a slight decrease in blood pressure. Thus pre

Parat dilates the coronary vessels and increases the speed of blood flow, improves the supply of oxygen to the myocardium. In general, the drug is considered a weak antiplatelet agent.

Indications for use:

1) to prevent thrombosis;

2) in the treatment of patients with DIC syndrome (in combination

with heparin);

3) for the prevention of DIC syndrome during infectious diseases

toxicosis, septicemia (shock);

4) during dehydration;

5) in patients with prosthetic heart valves;

6) during hemodialysis;

7) for angina pectoris and myocardial infarction.

Side effects: short-term redness of the face, tachycardia, allergic reactions. A modern antiplatelet agent is the drug TICLOPIDINE (Ticlopidinum; synonym - ticlid; in tablets of 0.25) - a new selective antiplatelet agent that is superior in potency to ASA.

Tiklid inhibits platelet aggregation and adhesion. The drug stimulates the formation of prostaglandins Pg E1, Pg D2 and Pg J2, improves microcirculation.

Indications for use:

1) ischemic and cerebrovascular diseases;

3) ischemia of the limbs;

4) retinopathy (diabetes mellitus, etc.);

5) when shunting blood vessels.

Side effects: stomach pain, diarrhea, rash, dizziness, jaundice, decreased white blood cell and platelet counts.

Plasma replacement drugs based on dextran, that is, low molecular weight dextrans (glucose polymers), are also used as antiplatelet agents. These are, first of all, solutions of the medium molecular fraction of dextran: 6% solution of polyglucin, 10% solution of reopolyglucin (especially this drug), as well as reogluman, rondex. These agents “dilute” the blood, reduce its viscosity, envelop platelets and red blood cells, which contributes to their antiplatelet effect, improve the movement of fluid from tissues to vessels, increase blood pressure, and have a detoxification effect.

Indications for use: shock, thrombosis, thrombophlebitis, endarteritis, peritonitis, etc. (to improve capillary blood flow).

Side effects: allergic reactions.

Platelet antiplatelet agents are drugs from the methylxanthine group: aminophylline, as well as teonicol (xanthinol nicotinate, complavin, xavin), etc.

TEONIKOL (xanthinol nicotinate; in tablets 0, 15 and

amp. 2 and 10 ml of 15% solution) has a vasodilating effect, improves cerebral circulation, and reduces platelet aggregation.

Indications for use:

1) vascular spasms of the extremities (endoarteritis, disease

2) trophic ulcers of the extremities.

Side effects: feeling of warmth, redness of the face, neck, general weakness, dizziness, pressure in the head, dyspepsia.

MEDICINES INTERPENDING RED CYTE AGGREGATION

PENTOXYPHYLLINE or trental (Pentoxyphillinum; in tablets of 0, 1 and in amps of 5 ml of 2% solution) is a derivative of dimethylxanthine, similar to theobromine. The main effect of the drug is to improve the rheological properties of blood. It promotes the bendability of red blood cells, which improves their passage through the capillaries (the diameter of red blood cells is 7 microns, and the diameter of capillaries is 5 microns).

Since trental increases the bendability of red blood cells, limits the aggregation of blood cells, and reduces the level of fibrinogen, it ultimately reduces the viscosity of the blood and makes it more fluid, reducing resistance to blood flow. Improvement in the rheological properties of blood occurs slowly. The effect occurs after 2-4 weeks.

Indications for use:

1) for peripheral circulatory disorders:

Raynaud's disease;

Diabetic angiopathy;

Vascular pathology of the eye;

2) for disorders of the cerebral and coronary blood flow

3) with circulatory shock.

Trental is contraindicated during pregnancy, in patients with hemorrhages and myocardial infarction. Undesirable effects: nausea, anorexia, diarrhea, dizziness, facial flushing.

DRUGS AFFECTING BLOODOOSIS

ANTIANEMIC DRUGS

Antianemic drugs are used to enhance hematopoiesis and eliminate qualitative disorders of erythropoiesis.

Anemia can develop as a result of insufficiency of various hematopoietic factors:

Iron (iron deficiency anemia);

Some vitamins (B12 deficiency, folate deficiency

cit, E-deficient);

Protein (protein deficiency).

In addition, the role of hereditary disorders of erythropoiesis, copper and magnesium deficiency is very significant. There are hypochromic and hyperchromic anemias. Hyperchromic anemia occurs due to a deficiency of B vitamins (folic acid - Bc and cyanocobalamin - B12). All other anemias are hypochromic. The incidence of anemia is high, especially among pregnant women.

ANTIANEMIC DRUGS USED FOR

HYPOCHROMIC ANEMIA

Most often, hypochromic anemia is of iron deficiency origin. Iron deficiency may result from:

Insufficient supply of iron to the fetus

and child;

Poor absorption from the intestine (mal syndrome

absorption, inflammatory bowel disease,

taking tetracyclines and other antibiotics);

Excessive blood loss (helminthic infestation, nasal and

hemorrhoidal bleeding);

Increased iron consumption (intensive growth, in

Iron is an essential component of a number of enzymes of both hemin and non-hemin structures. Hemin enzymes: - hemo- and myoglobin;

Cytochromes (P-450);

Peroxidases;

Catalase.

Non-heme enzymes: - succinate dehydrogenase;

Acetyl-CoA dehydrogenase;

NADH dehydrogenase etc.

With a lack of iron, the hemoglobin content decreases (the color index is less than one), as well as the activity of respiratory enzymes in tissues (hypotrophy).

Iron is absorbed in the duodenum, as well as in other parts of the small intestine. Ferrous iron is well absorbed. Trivalent iron received from food is converted into divalent iron under the influence of hydrochloric acid of the stomach. Calcium, phosphates contained in milk, especially cow's milk, phytic acid, tetracyclines interfere with the absorption of iron. The maximum amount of iron (ferrous that can enter the body per day is 100 mg).

Iron is absorbed in two stages:

Stage I: iron is captured by mucosal cells.

This process is supported by folic acid

Stage II: transport of iron through the cell

zistoy and release it into the blood. Iron in the blood

oxidizes to trivalent, binds to

transferrin.

The more severe the iron deficiency anemia, the less saturated this protein is and the greater its capacity and ability to bind iron. Transferrin transports iron to hematopoietic organs (bone marrow) or storage organs (liver, spleen).

To treat patients with hypochromic anemia, drugs are used, prescribed both orally and by injection.

Preferably ferrous iron preparations are used internally, as it is better absorbed and less irritating to the mucous membrane.

In turn, drugs prescribed orally are divided into:

1. Organic iron preparations:

Iron lactate; - ferrocal;

Gemostimulin; - ferroplex;

Conferon; - ferrocerone;

Aloe syrup with iron; - ferramide.

2. Inorganic iron preparations:

Ferrous sulfate;

Ferric chloride;

Iron carbonate.

The most accessible and cheapest drug is ferrous iron sulfate (Ferrosi sulfas; tablets of 0.2 (60 mg iron)) and powders in gelatin capsules of 0.5 (200 mg iron)). This preparation contains a high concentration of pure iron.

In addition to this drug, there are many others. IRON LACTATE (Ferri lactas; in gelatin capsules 0.1-0.5 (1.0-190 mg iron)).

ALOE SYRUP WITH IRON (in 100 ml bottles) contains a 20% solution of ferrous chloride, citric acid, aloe juice. Use one teaspoon per dose in a quarter glass of water. Among the undesirable effects when taking this drug, dyspepsia is common.

FERROCAL (Ferrocallum; a combined official preparation containing in one tablet 0.2 ferrous iron, 0.1 calcium fructose diphosphate and cerebrolecithin). The drug is prescribed three times a day.

FERROPLEX is a dragee containing ferrous sulfate and ascorbic acid. The latter sharply increases iron absorption.

The drug FEFOL is a combination of iron and folic acid.

Prolongiro drugs are considered more modern

bath action (TARDIFERON, FERRO - GRADUMET), manufactured using a special technology on an inert plastic sponge-like substance, from which iron is gradually released.

There are many drugs, you can use any, but you must remember that the therapeutic effect does not develop immediately, but after 3-4 weeks of taking the medicine. Repeated courses are often required. This means that side effects are primarily associated with the irritating effect of iron ions on the gastrointestinal mucosa (diarrhea, nausea). 10% of patients develop constipation because ferrous iron binds hydrogen sulfide, which is a natural irritant of the gastrointestinal tract. There is staining of the teeth. Poisoning is possible, especially in children (sweet, colored capsules).

Iron Poisoning Clinic:

1) vomiting, diarrhea (stool turns black

2) blood pressure drops, tachycardia appears;

3) acidosis, shock, hypoxia, gastroenterocco develops

The fight against acidosis is gastric lavage (3% soda solution). There is an antidote, which is a complexone. This is DEFEROXAMINE (desferal), which is also used for chronic aluminum poisoning. It is prescribed orally, intramuscularly or intravenously at a dose of 60 mg/kg per day. 5-10 grams are prescribed orally. If this drug is not available, then you can prescribe TETACIN-CALCIUM intravenously.

Only in the most severe cases of hypochromic anemia, when iron absorption is impaired, do they resort to drugs for parenteral administration.

FERKOVEN (Fercovenum) is administered intravenously, contains divalent iron and cobalt. When administered, the drug causes pain along the vein, thrombosis and thrombophlebitis are possible, chest pain and facial hyperemia may appear. the drug is very toxic.

FERRUM-LEK (Ferrum-lec; in amp. 2 and 5 ml) is a foreign drug for intramuscular and intravenous administration containing 100 mg of ferric iron in combination with maltose. The ampoules for intravenous administration contain 100 mg of iron sucrose. The drug for intramuscular injection cannot be used for intravenous administration. When prescribing the drug into a vein, the drug should be administered slowly; the contents of the ampoule must first be diluted in 10 ml of an isotonic solution.

When treating patients with hyperchromic anemia, vitamin preparations are used:

Vitamin B12 (cyanocobalamin);

Vitamin BC (folic acid).

Cyanocobalamin is synthesized in the body by intestinal microflora and is also supplied with meat and dairy foods. In the liver, vitamin B12 is converted into coenzyme cobamide, which is part of various reducing enzymes, in particular reductase, which converts inactive folic acid into biologically active folinic acid.

Thus, vitamin B12:

1) activates hematopoietic processes;

2) activates tissue regeneration;

Cobamamide, in turn, is necessary for the formation of deoxyribose and promotes:

3) DNA synthesis;

4) completion of red blood cell synthesis;

5) maintaining the activity of sulfhydryl groups in

glutathione, which protects red blood cells from hemolysis;

6) improvement of myelin synthesis.

To absorb vitamin B12 from food, intrinsic Castle factor is needed in the stomach. In its absence, immature red blood cells appear in the blood - megaloblasts.

Vitamin B12 preparation CYANOCOBALAMIN (Cianocobalaminum; dispensed in 1 ml amps of 0.003%, 0.01%, 0.02% and 0.05% solution) is a means of replacement therapy, administered parenterally. In its structure, the drug has cyanide and cobalt groups.

The drug is indicated:

For malignant megaloblastic anemia

Dison-Biermer and after resection of the stomach and intestines;

With diphylbothriasis in children;

With terminal ileitis;

For diverticulosis, sprue, celiac disease;

For long-term intestinal infections;

In the treatment of malnutrition in premature infants;

For radiculitis (improves myelin synthesis);

For hepatitis, intoxication (promotes the formation of

the presence of choline, which prevents the formation of fat in

hepatocytes);

For neuritis, paralysis.

Folic acid (vitamin Bc) is also used for hyperchromic anemia. Its main source is intestinal microflora. It also comes from food (beans, spinach, asparagus, lettuce; egg whites, yeast, liver). In the body, it is converted into tetrahydrofolic (folinic) acid, necessary for the synthesis of nucleic acids and proteins. This transformation occurs under the influence of reductases activated by vitamin B12, ascorbic acid and biotin.

The influence of folinic acid on the division of cells of rapidly proliferating tissues - hematopoietic and blood cells - is especially important.

zestous membrane of the gastrointestinal tract. Folinic acid is necessary for the synthesis of hemoproteins, in particular hemoglobin. It stimulates erythro-, leuko- and thrombocytopoiesis. In chronic folic acid deficiency, macrocytic anemia develops; in acute deficiency, agranulocytosis and aleukia develop.

Indications for use:

Mandatory together with cyanocobalamin for megalob

plastic Addison-Birmer anemia;

During pregnancy and lactation;

When treating patients with iron deficiency anemia,

since folic acid is necessary for normal

absorption of iron and its inclusion in hemoglobin;

For non-hereditary leukopenia, agranulocytosis,

some thrombocytopenias;

When prescribing drugs to patients that depress

intestinal flora that synthesizes this vitamin (antibi

otics, sulfonamides), as well as agents that stimulate

neutralizing liver function (antiepileptic

tic agents: diphenin, phenobarbital);

For children in the treatment of malnutrition (protein synthesizing

function);

In the treatment of patients with peptic ulcer (regenerator

function).

DRUGS STIMULATING LEUKOPOIESIS

Stimulators of leukopoiesis are prescribed for various types of leukopenia, agranulocytosis (with radiation injuries, severe infectious diseases) and are contraindicated in malignant processes of the hematopoietic system.

SODIUM NUCLEINATE (available in the form of powders. Prescribed 0.5-0.6 three times a day after meals. The course of treatment is 10 days. Stimulates leukopoiesis, increases the activity of phagocytes, increases the body's resistance. There are practically no side effects.

PENTOXIL (in tablets of 0, 2). METHYLURACIL (powders, tablets 0.5, suppositories with methyluracil 0.5, 10% methyluracil ointment 25.0). Pentoxyl and methyluracil are pyridine derivatives. The drugs have anabolic and anti-catabolic activity. They accelerate the processes of regeneration and wound healing, stimulate cellular and humoral protection factors. An important fact is that compounds of this series stimulate erythro-, but especially leukopoiesis, which is the basis for classifying these drugs into the group of leukopoiesis stimulants.

Drugs are indicated:

For agranulocytic sore throat;

For toxic aleukia;

For leukopenia as a result of chemotherapy and radiation therapy

PI for cancer patients;

For slow healing wounds, ulcers, burns, fractures

For stomach and duodenal ulcers;

For infectious diseases occurring with neutro

singing and inhibition of phagocytosis, in mild forms

leukopenia.

Pentoxyl is not used topically due to its irritating effect. A more modern remedy is one obtained using recombinant technology. In this regard, the best means of stimulating various germs of hematopoiesis is the drug MOLGRAMOSTIMUM or LEUCOMAX. This is a recombinant human granulocyte-macrophage colony-stimulating factor that activates mature myeloid cells, stimulating the proliferation and differentiation of precursor cells of the hematopoietic system. The drug leads to an increase in the content of granulocytes, monocytes and T-lymphocytes. After a single injection of Leucomax, this effect appears after 4 hours and reaches its peak after 6-12 hours. Leucomax enhances the phagocytosis of neutrophils.

The drug is used for the prevention and correction of neutropenia:

In patients receiving myelosuppressive therapy

(oncology);

In patients with aplastic anemia;

In patients after bone marrow transplantation;

In patients with various infections, including HIV-in

When treating patients with cytomegalovir with ganciclovir

Russian retinitis.