Heparin

General characteristics. Structure:

Active agent: Heparin sodium - 5000 ME Excipients: benzyl alcohol (benzyl alcohol) - 9,0 mg, sodium chloride - 3,4 mg, water for injections - to 1 ml.

Pharmacological properties:

Anticoagulant of direct action, concerns to group of middlemolecular heparins, slows down formation of fibrin. The anticoagulating effect is found in vitro and in vivo, comes directly after intravenous use.
The mechanism of effect of heparin is based first of all on its linkng with antithrombin III - inhibitor of the activated blood-coagulation factors: thrombin, IXa, Xa, XIa, XIIa (ability to inhibit thrombin and the activated factor of X is especially important). Heparin breaks transition of a prothrombin to thrombin, thrombin oppresses and stops formation of fibrin from fibrinogen, and also somewhat reduces aggregation of thrombocytes.
Increases a renal blood stream; increases brain vascular resistance, reduces activity of brain hyaluronidase, activates lipoproteinlipase and possesses hypolipidemic action.
Reduces activity of surfactant in lungs, suppresses excessive synthesis of Aldosteronum in bark of adrenal glands, connects adrenaline, modulates reaction of ovaries to hormonal incentives, increases activity of parathormone. As a result of interaction with enzymes can increase activity of a tyrosinehydroxylase of a brain, a pepsinogen, DNA polymerase and to reduce miozinovy Atfaza's activity, pyruvatekinases, RNA polymerases, pepsin.
At patients with coronary 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 thromboembolisms of a pulmonary artery and venous thrombosis, in small - for prevention of venous thromboembolisms, including after surgeries.
At intravenous administration a blood coagulation is slowed down almost at once, at intramuscular - in 15-30 min., at hypodermic - in 20-60 min., after inhalation at most of effect - in a day; duration of anti-coagulative effect respectively - 4-5, 6, 8 h and 1-2 weeks, therapeutic effect - prevention of a thrombogenesis - remains much longer.
Deficit of antithrombin III in plasma or in the place of thrombosis can reduce antitrombotichesky effect of heparin.

Pharmacokinetics. After hypodermic introduction of TCmax - 4-5 h. Communication with proteins of plasma - to 95%, distribution volume very small - 0.06 l/kg (does not leave a vascular bed because of strong linkng with proteins of plasma). Does not get through a placenta and into breast milk. It is intensively taken endothelial cells and cells of mononuklearno-macrophagic system (cells of reticuloendothelial 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: these cells are the main place of deposition of heparin from which it is gradually released, maintaining necessary concentration in plasma.
It is metabolized in a liver with participation of N-desulfamidazy and haparinase of thrombocytes joining in metabolism of heparin at later stages. Participation in metabolism of a platelet factor of IV (an anti-heparin factor), and also linkng of heparin with system of macrophages explain a bystry biological inactivation and short duration of action. Desulfatirovanny molecules under the influence of endoglycosidase of kidneys turn into low-molecular fragments. A drug elimination half-life - 1-6 h (on average - 1.5 h); increases at obesity, a liver and/or renal failure; decreases at a thromboembolism of a pulmonary artery, infections, malignant tumors.
It is allocated with kidneys, it is preferential in the form of inactive metabolites, and only at introduction of high doses removal (to 50%) in not changed look is possible. It is not removed by means of a hemodialysis.

Indications to use:

Prevention and therapy: a deep vein thrombosis, a thromboembolism of a pulmonary artery (including at diseases of peripheral veins), thrombosis of coronary arteries, thrombophlebitises, unstable stenocardia, an acute myocardial infarction, a ciliary arrhythmia (including followed by embolization), the IDCS, prevention and therapy of a microthrombogenesis and disturbance of microcirculation, fibrinferments of renal veins, a gemolitikouremichesky syndrome, mitral heart disease (prevention of a thrombogenesis), a bacterial endocarditis, a glomerulonephritis, lupoid nephrite.
Prevention of a blood coagulation during operations with use of extracorporal methods of blood circulation, when carrying out a hemodialysis, hemosorption, peritoneal dialysis, a cytapheresis, artificial diuresis, when washing venous catheters.

Route of administration and doses:

Heparin is appointed in the form of continuous intravenous infusion or in the form of regular intravenous injections, and also subcutaneously (to the area of a stomach).
With the preventive purpose - subcutaneously, on 5000 ME/days, bucketed in 8-12 h. The usual place for п / to injections is the anterolateral wall of a stomach (in exceptional cases enter into the upper area of a shoulder or hip), at the same time use a fine needle which should be entered deeply, perpendicularly, pleated skin, withheld between a big and index finger before the end of administration of solution. It is necessary to alternate every time injection sites (in order to avoid formation of a hematoma). The first injection needs to be carried out for 1-2 h prior to operation; in the postoperative period to enter within 7-10 days, and in case of need - longer time.
The initial dose of the heparin entered in the medical purposes usually makes 5000 ME and is entered intravenously then treatment is continued, using intravenous infusions.
Maintenance doses are defined depending on a route of administration:
- at continuous intravenous infusion appoint on 1000-2000 ME/h (24000-48000 ME/days), dissolving heparin in 0.9% chloride sodium solution;
- at periodic intravenous injections each 4 h appoint 5000-10000 ME heparins.
The adult at fibrinferments of easy and moderate severity drug is appointed intravenously in the dose of 40000-50000 ME/days divided into 3-4 times; at heavy thrombosis and an embolism - intravenously in the dose of 80000 ME/days divided into 4 times with an interval of 6 h. According to vital indications intravenously enter once 25000 ME (5 ml), then 20000 ME each 4 p before achievement of a daily dose of 80000 - 120000 ME. At intravenous drop injection to the daily volume of infusion solution it is necessary добалять not less than 40000 ME of heparin.
Heparin doses at intravenous administration select so that the activated partial tromboplastinovy time (APTT) was - 1.5-2.5 times more than control. At hypodermic introduction of small doses (5000 ME 2-3 times a day) for prevention of a thrombogenesis of regular control of AChTV it is not required since it increases slightly.
Continuous intravenous infusion is most efficiently heparin uses, the best, than regular (periodic) injections since provides stabler hypocoagulation and less often causes bleedings.
When carrying out extracorporal blood circulation enter in a dose of 140-400 ME/kg or on 1500-2000 ME on 500 ml of blood. At a hemodialysis enter intravenously 10000 ME in the beginning, then in the middle of the procedure - 30000-50000 more ME. For elderly people, especially women, doses have to be lowered.
To children the drug is administered intravenously kapelno: at the age of 1-3 months - 800 МЕ/кг/сут, 4-12 months - 700 МЕ/кг/сут, are more senior than 6 years - 500 МЕ/кг/сут under control of AChTV.

Features of use:

Drug heparin needs to be stored in the dark place at a low temperature.

Side effects:

In the course of use of this means it is necessary to consider probability of emergence of bleedings always. To warn possible complications, heparin needs to be accepted only in stationary conditions. At threat of hypocoagulation the dose of medicine goes down.

It is necessary to stop therapy if there are various allergic reactions, or the intolerance of drug is shown.

Contraindications:

Hypersensitivity to heparin, the diseases which are followed by the raised bleeding (hemophilia, thrombocytopenia, a vasculitis, etc.), bleeding, aneurism of vessels of a brain, the stratifying aortic aneurysm, a hemorrhagic stroke, an anti-phospholipidic syndrome, an injury (especially cherpno-brain), uncontrollable arterial hypertension, digestive tract erosive cankers; the cirrhosis which is followed by a gullet varicosity; the menstrual period, the menacing abortion, childbirth (including recent), recently carried out surgical interventions in the eyes, a brain, a prostate gland, a liver and bilious ways, a state after a puncture of a spinal cord, pregnancy, the lactation period. 
Use at pregnancy is not specified.

Storage conditions:

To store in the dry, protected from light place at a temperature from 8 to 15 °C. To store in the places unavailable to children. 
Period of validity 4 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

In hermetically sealed bottles on 5 ml with activity 5000; 10 000 and 20 000 PIECES in 1 ml. Injection solution in ampoules on 0,1 ml. Geparibene-Na-5000 syringe tubes. One unit-dose syringe from 0,2 ml of injection solution. Geparibene-Na-25 000th bottles. One punctured bottle from 5 ml of injection solution.