Heparin

General characteristics. Structure:

Active ingredient: 5000 UI heparin sodium (in terms of heparin) in 1 ml of solution.

Anticoagulating drug of pramy action.

Pharmacological properties:

Pharmacodynamics. Communicates antithrombin III, causes conformational changes in its molecule and accelerates an antithrombin III kompleksirovaniye with serineproteases of system of coagulation; thrombin, enzymatic activity of the activated factors of IX, X, by XI, XII, plasmin and kallikrein is as a result blocked.

Connects thrombin; this reaction has the electrostatic nature and substantially depends on heparin molecule length; only a small part of a molecule of heparin has affinity with ATIII, as provides generally its anti-coagulative activity. Thrombin braking by antithrombin — slow process; formation of a complex geparin-ATIII considerably accelerates due to direct binding of heparin gamma аминолизиловыми parts of the molecule ATIII and owing to interaction between thrombin (through serine) and a complex geparin-ATIII (through arginine); after completion of reaction of braking of thrombin heparin is released from a complex geparin-ATIII and can be used by an organism again, and the remaining complexes are removed endothelial system; reduces viscosity of blood, reduces permeability of vessels, stimulated bradikinin, a histamine and other internal causes, and interferes thus with development of a staz; on a surface of cells of an endothelium special receptors for endogenous analogs of heparin are found; 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 ATIII cause braking of a hyperplasia of unstriated muscles, including due to braking of adhesion of thrombocytes with oppression of release of a growth factor of these cells, suppress activation of a lipoproteidlipaza, than interfere with development of atherosclerosis; heparin connects some components of system of a complement, lowering its activity, interferes with cooperation of lymphocytes and formation of immunoglobulins, connects a histamine, serotonin — all this causes antiallergic effect; interacts with surfactant, reducing its activity in lungs; has influence on endocrine system — 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 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; at in introduction a blood coagulation is slowed down almost at once, at in oil — cherez15-30min, at п / to — in 40–60 min., after inhalation at most of effect — in a day; duration of anti-coagulative effect respectively — 4–5 h, 6 h, 8 h, 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 limit antitrombotichesky effect of heparin.

Pharmacokinetics. The highest bioavailability is noted at in introduction; at п / to introduction bioavailability low, Cmax in plasma is reached in 2–4 h; T1/2 makes 1–2 h of plasma; in plasma is in the basic in the state connected with proteins; it is intensively taken endothelial cells and 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: these cells are the main place of deposition of heparin from which it is gradually released, supporting a certain level in plasma; is exposed to a desulfatation under the influence of N-desulfamidazy and the haparinase of thrombocytes joining in metabolism of heparin at later stages; desulfatirovanny molecules under the influence of endoglycosidase of kidneys turn into low-molecular fragments. Excretion occurs through kidneys in the form of metabolites, and only at introduction of high doses excretion in not changed look is possible. Does not pass through a placental barrier, it is not excreted in breast milk.

At external use the insignificant amount of heparin is absorbed from the surface of skin in a system blood stream. Cmax in blood is noted in 8 h after application.

Indications to use:

Parenterally: unstable stenocardia, acute myocardial infarction; tromboembolic episodes at a myocardial infarction, heart operations and blood vessels, a thromboembolism of a pulmonary artery (including at diseases of peripheral veins), thrombosis of coronary arteries and brain vessels, thrombophlebitis (prevention and treatment); IDCS, prevention and therapy of a microthrombogenesis and disturbance of microcirculation; deep vein thrombosis; thrombosis of renal veins; gemolitiko-uraemic syndrome; a ciliary arrhythmia (including followed by embolization), mitral heart disease (prevention of a thrombogenesis); bacterial endocarditis; glomerulonephritis; lupoid nephrite. Prevention of a blood coagulation when carrying out extracorporal methods (extracorporal blood circulation at heart operation, hemosorption, a hemodialysis, peritoneal dialysis, a cytapheresis), an artificial diuresis; washing of venous catheters.

Outwardly: the migrating phlebitis (including at a chronic varicosis and varicose ulcers), thrombophlebitis of superficial veins, local hypostasis and aseptic infiltrate, complications after surgeries on veins, a hypodermic hematoma (including after a phlebectomy), injuries, bruises of joints, sinews, muscular tissue.

Route of administration and doses:

П / to, in/in, outwardly. The dosing mode individual, depending on the applied dosage form, indications, a clinical situation and age of the patient.

Features of use:

Use at pregnancy and feeding by a breast. At pregnancy and during breastfeeding it is possible only according to strict indications. Category of action on a fruit on FDA — C.

Constant control of a blood clotting time is necessary; cancellation has to be carried out gradually.

At external use it is not necessary to apply on open wounds, on mucous membranes. Gel is not appointed along with NPVS, tetracyclines, antihistaminic HP.

Side effects:

System effects. From a nervous system and sense bodys: dizziness, headache.

From cardiovascular system and blood (a hemopoiesis, a hemostasis): thrombocytopenia (6% of patients) — early (2–4 days of treatment) and late (autoimmune), in rare instances with a lethal outcome; hemorrhagic complications — bleedings from a GIT or urinary tract, retroperitoneal hemorrhages in ovaries, adrenal glands (with development of acute adrenal insufficiency).

From bodies of a GIT: a loss of appetite, nausea, vomiting, diarrhea, increase in level of transaminases in blood.

Allergic reactions: dermahemia, medicinal fever, small tortoiseshell, rash, skin itch, bronchospasm, anaphylactoid reactions, acute anaphylaxis.

Others: at prolonged use — an alopecia, osteoporosis, calcification of soft tissues, oppression of synthesis of Aldosteronum; injection reactions — irritation, a hematoma, morbidity at introduction.

At external use: dermahemia, allergic reactions.

Interaction with other medicines:

Efficiency of heparin sodium amplifies acetylsalicylic acid, a dextran, phenylbutazone, an ibuprofen, indometacin, Dipiridamolum, hydroxychloroquine, warfarin, dikumaroly — the risk of bleedings (at combined use it is necessary to be careful) increases, it is weakened — cardiac glycosides, tetracyclines, nicotine, antihistaminic drugs, changes — niacin.

Combined use of heparin sodium (including in the form of gel) with indirect anticoagulants can cause lengthening of PV. The risk of bleeding at a combination to diclofenac increases and ketorolaky at parenteral administration (to avoid a combination, including heparin in low doses). Klopidogrel increases risk of bleeding.

Contraindications:

Hypersensitivity; for parenteral use: hemorrhagic diathesis, hemophilia, a vasculitis, thrombocytopenia (including caused by heparin in a vnvmneza), bleeding, a leukosis, a hyperpermeability of vessels, polyps, malignant new growths and cankers of a GIT, a gullet varicosity, heavy uncontrollable arterial hypertension, an acute bacterial endocarditis, an injury (especially craniocereberal), recently postponed surgical intervention in the eyes, a brain and a backbone, heavy abnormal liver functions and/or kidneys.

For external use: ulcer and necrotic, purulent processes on skin, traumatic disturbance of integrity of integuments.

Restrictions to use. For external use: the increased tendency to bleeding, thrombocytopenia.

Storage conditions:

To store at a temperature of 2-8 °C, in dry, protected from light and the place, unavailable to children. Period of validity 3 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Solution for injections of 5000 UI/ml, on 5 ml in each ampoule or a bottle. On 5 or on 10 ampoules, or on 1 or 5 bottles in cardboard packaging.