Heparin

General characteristics. Structure:

Active ingredient: 5000 PIECES of heparin in 1 ml of solution.

Pharmacological properties:

Pharmacodynamics. Heparin is anticoagulant of direct action. Contacts antithrombin III, causes conformational changes in its molecule and accelerates an antithrombin III kompleksirovaniye with serinovy proteases of system of coagulation; thrombin, enzymatic activity of factors of IX, X, by XI, XII, plasmin and kallikrein is as a result blocked. Heparin has no thrombolytic effect. Introduction to drug blood in small doses is followed by slight and non-constant increase of fibrinolitic activity of blood; high doses of heparin cause, as a rule, braking of a fibrinolysis.

Heparin reduces viscosity of blood, interferes with development of a staz. Heparin is capable to be occluded of surfaces of membranes of an endothelium and uniform elements of blood, increasing their negative charge that interferes with adhesion and aggregation of thrombocytes, erythrocytes, leukocytes. The heparin molecules having low affinity with antithrombin III cause braking of a hyperplasia of unstriated muscles, and also suppress lipoproteinlipase activation, than interfere with development of atherosclerosis. Heparin has antiallergic effect: connects some components of system of a complement, lowering its activity, interferes with cooperation of lymphocytes and formation of immunoglobulins, connects a histamine, serotonin. Activity of hyaluronidase oppresses. Has weak vasodilating effect.

At patients with an ischemic heart disease (in a combination with acetylsalicylic acid) reduces risk of development of acute thromboses of coronary arteries, a myocardial infarction and sudden death. Reduces the frequency of repeated heart attacks and a lethality of the patients who had a myocardial infarction. In high doses it is effective at embolisms of pulmonary vessels and venous thrombosis, in small – for prevention of venous thromboembolisms, including after surgeries.

Heparin works quickly, but is rather short-term. At intravenous administration a blood coagulation is slowed down almost at once, at intramuscular – in 15 - 30 min., at hypodermic introduction – in 40 - 60 min., after inhalation the maximum effect is observed in a day; duration of anti-coagulative effect, respectively, makes 4 - 5 h, 6 h, 8 h, 1 - 2 weeks, therapeutic effect (prevention of a thrombogenesis) remain much longer. Deficit of antithrombin III in plasma or in the place of thrombosis can limit antitrombotichesky effect of heparin.

Pharmacokinetics. At hypodermic introduction bioavailability low, Cmax is reached in 2 - 4 h; T1/2 makes 1 - 2 h. In plasma heparin is in the basic in the state connected with proteins; it is intensively taken endothelial cells of mononuklearno-macrophagic system, concentrates in a liver and a spleen; at an inhalation way of introduction it is absorbed by alveolar macrophages, an endothelium of capillaries, big circulatory and absorbent vessels.

Is exposed to a desulfatirovaniye under the influence of N-desulfamidazy and a haparinase of thrombocytes. Desulfatirovanny molecules under the influence of endoglycosidase of kidneys turn into low-molecular fragments. It is excreted by kidneys in the form of metabolites, and only at introduction of high doses excretion in not changed look is possible. Heparin badly gets through a placenta owing to big molecular weight. It is not allocated with breast milk.

Indications to use:

Unstable stenocardia, acute myocardial infarction, tromboembolic episodes at a myocardial infarction, heart operations and blood vessels, a thromboembolism of pulmonary and brain vessels, thrombophlebitises (prevention and treatment), the IDCS, prevention of a microthrombogenesis and disturbance of microcirculation, fibrinferments of renal veins, a gemolitiko-uraemic syndrome, a ciliary arrhythmia, mitral heart diseases (prevention of a thrombogenesis), a bacterial endocarditis, a glomerulonephritis, lupoid nephrite, rheumatism, bronchial asthma, carrying out extracorporal methods (an extracorporal krovobrashcheniye at heart operation, hemosorption, a hemodialysis, peritoneal dialysis, a cytapheresis), an artificial diuresis, washing of venous catheters.

Route of administration and doses:

Heparin is entered intravenously or intramusculary (every 4 hour), subcutaneously (every 8 — 12 hours) and in the form of intra arterial infusion, and also an electrophoresis method. At an acute myocardial infarction in the first day the first dose (10000 — 15000 PIECES) is entered intravenously, then continue fractional intravenous or intramuscular administration of drug in a dose of 40000 PIECES a day so that the blood clotting time by 2,5 — 3 times exceeded normal amounts. Since 2nd day, the daily dose makes 600 PIECES/kg of weight of the patient (30000 — 60000 PIECES), so that the blood clotting time was 1,5 — 2 times higher than norm. Treatment by heparin is continued within 4 — 8 days. For 1 — 2 day before heparin cancellation the daily dose is gradually lowered (daily by 5000 — 2500 PIECES on each injection without increase in intervals between them) before full drug withdrawal then carry out treatment only by anticoagulants of indirect action (neodicoumarin, Phenilinum, etc.) which appoint about 3 — 4 days of treatment.

When using heparin in complex conservative therapy of acute venous or arterial impassability begin with continuous intravenous drop infusion of drug within 3-5 days. The daily dose of heparin (400 — 450 PIECES/kg) is parted in 1200 ml of isotonic solution of sodium chloride or Solution Ringer-Locke and poured with a speed of 20 thaws a minute. Then heparin is entered fractionally in a dose of 600 PIECES/kg a day (on 100 PIECES/kg on one injection). At impossibility of intravenous administration of heparin, it is applied intramusculary or subcutaneously in a dose of 600 PIECES/kg a day. Geparinoterapiya 14 — 16 days continue. In 3 — 4 days prior to heparin cancellation the daily dose is lowered daily by 2500 — 1250 PIECES on each injection without increase in intervals between them. After drug withdrawal carry out treatment by anticoagulants of indirect action which appoint one day before the first dose decline of heparin.

At operational treatment of the specified diseases during operation just before a thrombectomy from the main veins or right after an emboltrombektomiya from arteries, heparin enter in a dose 100 PIECES/kg intravenously or vnutriarterialno. Then, within the first 3 — 5 days of the postoperative period enter heparin intravenously kapelno with a speed of 20 thaws a minute regionarno into a vein from which blood clot, in a dose of 200 — 250 PIECES/kg a day or intravenously in the general blood stream in a dose of 300 — 400 PIECES/kg a day was removed. Since 4 — 6 days after operation, the geparinoterapiya is carried out the same as at conservative treatment. After the operations performed concerning acute arterial impassability, the geparinoterapiya is continued within 10 — 12 days, and reduction of a dose of heparin there begin from 6 — 7 in the afternoon treatments.

In ophthalmologic practice heparin is used at all types of occlusion of vessels of a mesh cover of eyes, and also at all angiosclerotic and dystrophic processes of a vascular path and a retina of an eye. At acute impassability of vessels of a retina the first dose of heparin (5000 — 10000 PIECES) is entered intravenously. Further heparin is applied fractionally intramusculary on 20000 — 40000 PIECES a day. Treatment is carried out according to a clinical picture of a disease within 2 — 7 days. On the second - third day use of heparin in combination with anticoagulants of indirect action is possible.

At direct hemotransfusion heparin is entered to the donor in a dose of 7500 — 10000 PIECES intravenously.

Features of use:

Treatment by heparin needs to be carried out under careful control of a condition of hemocoagulation. Researches of a condition of a blood coagulation make: in the first 7 days of treatment — at least 1 time in 2 days, further 1 time in 3 days; in the first day of the postoperative period at least 2 times a day, in the 2nd and 3rd days — at least 1 time a day. At fractional administration of heparin blood samples for the analysis are taken just before a drug injection.

The sudden termination of a geparinoterapiya can lead to rough activation of trombotichesky process therefore the dose of heparin should be reduced gradually with co-administration of anticoagulants of indirect action. An exception are cases of emergence of heavy hemorrhagic complications and individual intolerance of heparin.

Hemorrhagic complications can arise at any including at a hypercoagulative condition of a blood coagulation. Treat measures of the prevention of hemorrhagic complications: heparin use only in the conditions of a hospital; restriction of quantity of injections (hypodermic and intramuscular), except for injections of the heparin; careful control of a condition of a blood coagulation; at identification of the menacing hypocoagulation — an immediate dose decline of heparin without increase in intervals between injections. In order to avoid formation of hematomas in places of injections it is better to use an intravenous technique of administration of heparin.

Side effects:

At use of heparin dizziness, headaches, nausea, anorexia, vomiting, an alopecia, early (2 — 4 days of treatment) and late (autoimmune) thrombocytopenia, hemorrhagic complications — bleedings in a GIT or in an uric path, retroperitoneal hemorrhages in ovaries, adrenal glands (with development of acute nadpochechenikovy insufficiency), osteoporosis, calcification of soft tissues, oppression of synthesis of Aldosteronum, increase in level of transaminases in blood, allergic reactions (fever, rashes, bronchial asthma, anaphylactoid reaction), local irritation, a hematoma, morbidity can be observed at introduction).

At individual intolerance and emergence of allergic complications heparin is cancelled immediately and appoint the desensibilizing means. In need of continuation of anticoagulating therapy apply anticoagulants of indirect action.

Depending on weight of the arisen hemorrhagic complication it is necessary or to reduce a heparin dose, or to cancel it. If after heparin cancellation bleeding proceeds, intravenously enter the antagonist of heparin — протаминсульфат (5 ml of 1% of solution). If necessary introduction of a protaminsulfat can be repeated.

Interaction with other medicines:

Effects of heparin amplify acetylsalicylic acid, a dextran, phenylbutazone, an ibuprofen, indometacin, warfarin, Dicumarinum (the risk of bleedings increases), are weakened — cardiac glycosides, tetracyclines, antihistaminic drugs, niacin, Acidum etacrynicum.

Contraindications:

Use of heparin is contraindicated at individual intolerance and the following states: bleedings of any localization, except for the hemorrhage which arose because of an embolic heart attack of a lung (pneumorrhagia) or kidneys (hamaturia); the hemorrhagic diathesis and other diseases which are followed by blood coagulation delay; a hyperpermeability of vessels, for example, at Verlgof's disease; the repeating bleedings in the anamnesis irrespective of their localization; subacute bacterial endocarditis; heavy abnormal liver functions and kidneys; acute and chronic leukoses, aplastic and hypoplastic anemias; to sharply developed heart aneurism; to venous gangrene.

Medicine will be applied with care in the following cases: at ulcer and tumoral gastrointestinal tract diseases, a cachexia irrespective of its etiology, the high arterial pressure (it is higher than 180/90 mm of mercury), in the next postoperative and puerperal period within the first 3 — 8 days (except for operations on blood vessels and when the geparinoterapiya is necessary according to vital indications).

The risk of adverse effects for pregnant women at use of heparin fluctuates from 10,4% to 21%. At the normal course of pregnancy it makes 3,6%. At heparin use the risk of a lethal outcome and premature births makes 2,5% and 6,8% and is similar to risk in natural population of the Effect of use of heparin during pregnancy can include: bleedings, thrombocytopenia, osteoporosis. The risk of development of tromboembolic episodes at pregnancy removed by use of heparin is more life-threatening therefore use of heparin at pregnancy is possible, but only according to strict indications, under careful medical control. Heparin does not get through a placenta and collateral influence on a fruit it is improbable. Use in the period of a lactation (breastfeeding) according to indications is possible.

Issue conditions:

According to the recipe

Packaging:

Solution for injections of 5000 PIECES/ml in bottles of 5 ml in packaging No. 5