Drugs affecting the blood system ( activity of myometrium )
Drugs affecting the tone and contractile activity of myometrium
Drugs affecting the blood system
The functions of myometrium are both regulated by sympathetic and parasympathetic nervous systems. At the activation of parasympathetic innervation contractions of myometrium become more intensive. The same effect is achieved at the activation of sympathetic α1-adrenoreceptors, while the stimulation of β2-adrenoreceptors by adrenalin leads to the decrease of tone and and contractile activity of myometrium. That is why selective drugs exert a direct action on uterus. Besides, in the fundus of the uterus there are pacemaker cells, generating impulses (autonomous nervous system) which cause constant rhythmic uterine contractions.
During menstruation these contractions intensify. At the same time blood vessels get compressed and ischemia of myometrium can be noticed, which is manifested by pain.
During pregnancy the contractile activity of myometrium is reduced under the influence of progesterone (produced by the yellow body) and later by placental hormone possessing similar properties.
Before the labor the number of oxytocin (the hormone of the posterior lobe of hypophysis) receptors in myometrium is increasing under the influence of estrogens. The level of the platelet-activating factor (PAF) which stimulates phospholipase А2 is getting higher increasing the level of prostaglandins Е2 and F2a. These prostaglandins and oxytocin induce the beginning of the labor, stimulate the labor activity and after the labor – increase the tone of myometrium causing the compression of vessels and hence the termination of uterine bleeding. The medications affecting uterus can firstly influence on endometrium or myometrium.
Classification of drugs affecting myometrium
- Drugs increasing rhythmic contractions and tone of myometrium: Oxytocin, Demoxytocin, Dinoprost, Dinoproston, Misoprostole, Gemeprost;
- Drugs increasing the tone of myometrium: Ergometrine, Methylergometrine, Ergotamine;
- Drugs decreasing rhythmic contractions and tone of myometrium: Salbutamol, Fenoterol, Hexoprenaline, Progesteron, Hydroxyprogesterone, magnesium sulphate, diethyl ether, ethanol.
Drugs increasing rhythmic contractions and tone of myometrium
This group includes the drugs of oxytocin and prostaglandins.Oxytocin is a hormone of the posterior lobe of hypophysis. Pharmacodynamics. It stimulates the rhythmic uterine contractions. In higher doses it increases the tone of myometrium. Nonpregnant uterus and the one in the beginning of the pregnancy are not very sensitive to the action of oxytocin. During pregnancy the sensitivity gradually becomes higher. Before the labor, during the labor and during the first day after the labor it is most prominent. In lactation period oxytocin stimulates lactation increasing the contraction of myoepithelial cells in the ducts of mammary glands. It exerts pressor and antidiuretic actions. Prescription. I/v, i/m and intranasal administration. For the induction and stimulation of labor it is administered with an i/v drip – 1-2МЕ in 400 ml of 5% glucose or i/m – 1 or 0,5МЕ with an interval of 30-60 min. To stimulate lactation one administers it i/m or intranasally – 0,5МЕ 5 minutes before breastfeeding.Adverse reactions. Nausea, vomiting, bradykardia, arrhythmia, arterial hypertension, fluid retention, bronchospasm, discoordinated labor, premature detachment of placenta, allergic reactions. Contraindications. Inadequacy in sizes of fetus and pelvis, oblique or transverse lie, risk of metrorrhexis, presence of scars on uterus after previous C-section, premature labor, renal failure, arterial hypertension, cardiovascular failure. Dosage forms. Solution for injections in 1 ml ampoules (5 or 10МЕ) and 2 ml (2МЕ).
Prostaglandin drugs
( 1 ) Dinоprost (Prostin F2a, Enzaprost-F)
Dinоprost (Prostin F2a, Enzaprost-F) is the main representative of prostaglandins used in obstetrics. Pharmacodynamics. It possesses a prominent stimulating effect on smooth muscles of uterus (increases the tone of myometrium, relaxes the uterine cervix). Stimulation of uterine contractions is possible at any term of pregnancy unlike in case of oxytocin. Prescription. The main administration routes for prostaglandins are: i/v, extraamnial, intraamnial, intravaginal. To induce the labor activity Dinoprost is administered by i/v drip in the dose of 0,001-0,005 g (1-5 mg) in 400 ml of 5% glucose or 0,09% solution of NaCl. Intravaginal – 0,005 g (5 mg) every 2 hours.Adverse reactions. Nausea, vomiting, diarrhea, tachycardia, bronchospasm, allergic reactions, if administered i/v – phlebitis, fever.Contraindications. In case of pregnancy with uterine scar, anatomical and clinically narrow pelvis, ulcerative colitis, heart failure, renal and hepatic diseases, deseases of blood formation, inclination to bronchospasm, glaucoma.Dosage form. 0,5% solution in ampoules – 1; 5 and 8 ml.
( 2 ) Ergot and its alkaloids
It exerts a stimulating action on uterine muscles. It is used in case of uterine insufficiency and uterine bleedings. The styptic effect is conditioned by the compression of the walls of vessels when the muscles contract. It is not used for the labor speeding-up. The main drugs of this group are: Ergometrine, Methylergometrine, Ergotamine, Ergotal.
( 3 ) Ergometrine (Metriclavin)
Pharmacodynamics. It affects the uterine muscles faster and more effectively than other alkaloids, increases the tone of uterus and increasing the rate of contractions. Prescription. P/o, i/m, i/v. Single dose for parenteral administration – 0.1-0.2 mg (0.5-1 ml of 0.02% solution), p/o - (1-2 tab) 2-3 times a day.Adverse reactions. Nausea, vomiting, pain in the region of heart, arterial hypertension, ergotism (disturbance of tissue trophism caused by a spasm). Contraindications. Pregnancy and labor.Dosage forms. Tablets – 0,0002 g (0,2 mg); 0,02% solution in 0.5 and 1 ml ampoules (0,1 and 0,2 mg).
Drugs affecting the blood system
Drugs affecting erythropoiesis
The stimulators of erythropoiesis: Epoetine, Cyanocobalamine, folic acid, iron drugs. Iron sulphate (Ferrosisulfas, Hemofer, prolonged action Ferrogradumet) is used in case of iron-deficient anemia and chronic posthemorrhagic anemia.Prescription. P/o (after meal) for adults – 0,3-0,5 g х 3-4 times daily. Prolonged Hemofer – 1 dragee х 1-2 times a day.Adverse reactions. Hyperthermia, skin hyperaemia, nausea, vomiting, constipation or diarrhea.Contraindications. Hemochromatosis, aplastic, hemolytic anemia, chronic hepatic and renal diseases, chronic inflammatory diseases, leukaemia.Dosage forms. Tablets – 0,105, 0,3 and 0,325 g. Dragee – 0,345 g and 0,325 g.
( 1 ) Co-amide
Pharmacpdynamics. Cobalt is a stimulator of blood formation. It facilitates the uptake of iron, stimulates the synthesis of hemoglobin, normalizes erythropoiesis, eliminate anemia. It used for the treatment of hypochromic, hypoplastic and other types of anemis which are resistant to iron drugs. Prescription. Administered s/c – in the form of 1% water solution, 1 ml daily. P/o – 0,1 g x 3 times daily.Dosage forms. 1% solution in 1 ml ampoules.
( 2 ) Cyanocobalamine, vitamin В12 (Cyanocobalaminum)
Pharmacodynamics. In the body it turns into a coenzyme – adenosylcobalamin or Cobamamide. The growth factor necessary for blood formation and maturation of erythrocytes. It activates the coagulatory blood system: increases thromboplastic activity and activity of prothrombin. It is a high-performance antianemic drug. It exerts a therapeutic effect for Addison-Biermer’s disease, agastric anemia, for anemia caused by gastric or intestinal diseases, for anemia conditioned by the invasion of broad tapeworm, pregnancy, for pernicious, posthemorrhagic, iron-deficient, aplastic anemia caused by toxic and substances and medicaments. Prescription. I/m, i/v, intralumbar administration. In case of anemis associated with the deficiency of vitamin В12 one administers 1-0,2 mg once in 2 days; in case of Addison-Biermer’s anemia with the involvement of nervous system – 0.5 mg. Simultaneously, one prescribes folic acid.Adverse reactions. Well-tolerated. Allergic reactions, nervous excitation, heartaches, tachycardia.Contraindications. Thrombosis, erythremia, erythrocytosis. С With caution – in case of angina.Drug interactions. It is not recommended to administer В1,and В6,together in one syringe because the containing cobalt ion facilitate the desintegration of other vitamins. Vitamin В12 can intensify the allergic reactions to vitamin В1.Dosage forms. 0,003%, 0,01%; 0,02%, 0,05% and 0,1% solutions in ampoules and 1 ml vials.
( 3 ) Folic acid (Acidumfolicum, Folacin)
Pharmacodynamics. In the body it is reduced to tetrahydrofolic acid which is a coenzyme. It is necessary for the normal blood cell formation including the processes of maturation of megaloblasts and synthesis of normoblasts. At the lack of folic acid megaloblasts appear in the blood. Together with vitamin В12 it stimulates erythropoiesis, participates in the synthesis of aminoacids (methionine, serine etc.), nucleic acids, purines and pyrimidines, in the metabolism of choline. It is used for the stimulation of erythropoiesis in case of macrocytic hyperchromic anemia, anemia caused by medications, ionizing radiation, anemia after gastrectomy, intestinal ectomy, alimentary macrocytic anemia in newborns. It is not very effective in case of aplastic anemia. It is also used for the chronic intestinal diseases. Prescription. Adults – 0,005 g (5 mg) daily. The course – 20-30 days. For the prevention of folic deficiency at unbalanced nutrition – 0,02-0,05 mg daily. Adverse reactions. Allergic reactions are possible.Drug interaction. Analgesics, antoconvulsants, antacids, antibiotics, sulfanilamides and cytostatics reduce the effect of folic acid. Dosage form. 0,001 g tablets (1 mg).
( 4 ) Epoetin alfa (Эпрекс) and Epoetin beta (Erythrostim, Recormon)recombinant drugs of human erythropoietin.
Pharmacodynamics. It stimulates mitosis and differentiation of erythroid cells-precursors, increase the number of erythrocytes as well as the level of hempglobin. It is used for anemia caused by bone marrow damage, chronic renal failure, during the treatment by Zidovudine in premature newborns. Pharmacokinetics. At the s/c administration bioavailibility – 25%. Сmax– 12 h,Т1/2 – up to 24 hours, at i/v administration – 5-6 h. Prescription. S/c or i/v administration (stream) at first normally 50-75 IU/kg 3 times a day.Adverse reaction. High arterial pressure, convulsions, thrombocytosis, thrombocytopenia, thromboembolic complications, hyperkaliemia, iron-deficient states, allergic reactions etc.Contraindications. Resistant arterial hypertension, pregnancy, lactation.Dosage form. Solution for injections in 1 ml ampoules (500, 2000, 4000, 10000 IU).
Drugs affecting leukopoiesis
timulators of leukopoiesis: the drugs of colony-stimulating factors, sodium nucleinate. 4 colony-stimulating factors (CSF) are differentiated among biogenic stimulators of leukopoiesis: granulocytic CSF (stimulates the production of neutrophils, eosinophils, basophils), macrophage CSF (stimulates the production of monocytes that turn into macrophages in tissues), , которые в тканях превращаются в макрофаги), granulocytic-macrophage CSF, interleukin-3 (universal CSF).
( 1 ) Filgrastim (Neupogen)
Filgrastim (Neupogen) is a polypeptide obtained by genetically engineered way via Eschеrichiacoli. It contains the gen of granulocytic human CSF.Pharmacodynamics. It stimulates granulocytopoiesis. It interacts with the receptors on the surface of hemopoietic cells, fasten the biosynthesis and release of neutrophils in the bone marrow. Prescription. I/v and s/c administration. Doses are adjusted individually. In case of cytotoxic neutropenia one administers 500000 IU/day.Adverse reactions. Side effects are rarely noticed. Pain in bone is possible as well as in muscles, skin redness and pain in the site of injection, allergic reactions.Dosage forms. Solution for injections in vials, syrettes – 30 and 48 mln IU. Administration – with 5% glucose.
( 2 ) Sodium nucleinate (Natriinucleinas)
Pharmacodynamics. It is used as an immunostimulating agent in complex therapy in case of diseases accompanied by the developing immunodeficiency, leukopenia and agranulocytosis included. Prescription. P/o (after meal) for adults a daily dose should contain1-2 g (in 3-4 intakes). The course of therapy – from 2 weeks to 3 months. The therapy is performed with the control over the immune status.Dosage forms. Powder in 0,5 g vials for p/o use.
Drug affecting the formation of thrombus
The formation of thrombus in arterial vessels starts with aggregation of thrombocytes induced by the damage to vascular endothelium. The aggregation process is followed by coagulation process – the formation of fibrin filaments that make a thrombus firmer.
The aggregation of thrombocytes is prevented by prostacyclin (prostacyclin I2), while coagulation – by antithrombin III and heparin. The formed thrombus may be dissolved under the influence of fibrinolysin (plasmin).
Drugs affecting the formation of a thrombus are divided into:- Drugs affecting the aggregation of thrombocytes;
- Drugs affecting blood coagulation;
- Drugs affecting fibrinolysis.
Antiaggregants prevent adhesion of thrombocytes – initial stage of thrombus formation, mainly in arterial vessels and less – in venous ones. Used for the prevention of thrombus formation.
( 1 ) Acetylsalicylic acid (Aspirin)
Acetylsalicylic acid (Aspirin) is a nonsteroid anti-inflammatory drug (NSAID). It exerts ani-inflammatory, anesthetic, anti-fever effects. For that purpose it is used in the dose 0,5-1 g/day.Pharmacodynamics. Administered p/o it irreversibly inhibits cyclooxygenase-1 in thrombocytes and vascular endothelium disturbing the formation of aggregants: thromboxane А2 and prostacyclin.Indications:- Acute myocardial infarction, starting from the first hours;
- Prevention of myocardial infarction;
- Instable angina;
- After coronary angioplasty and stenting of coronary vessels;
- Cerebral blood circulation disorder by ischemic type;
- Prevention of thromboformation at the atrial fibrillation and in case of contraindications for the use of coagulants;
- intermittent claudication.
Pharmacokinetics. After ingestion it is rapidly and completely absorbed. Т1/2 is no more than 15-20 min. It easily gets into tissues. Biotransformation in the intestinal and hepatic walls with the formation of salicylic acid. Eliminated by kidneys in an unchanged form.Prescription. Prominent reduction of aggregation is possible with the dose 75-325 mg/day. Most frequently prescribed - 0,1 g (100 mg) х once a day.Dosage forms. Tablets – 0,1 g, 0,25, 0,5 g.
( 2 ) Clopidogrel
Pharmacodynamics. It inhibits the aggregation of thrombocytes by blocking the binding of adenosine diphosphate to the receptors of thrombocytes. Maximum antiaggregant effect is achieved in 4-7 in the therapy and is maintained up to 4-10 days. Pharmacokinetics. Rapidly absorbed. Сmax – 1 h. Т1/2 – 8 h. Biotransformation – in liver with the formation of an active metabolite. Excreted with urine and feces. Prescriprion. P/o – 0,075 g once a day.Dosage forms. Tablets – 0,075 g (75 mg).
( 3 ) Ticlopedine
Pharmacodynamics. As an antiaggregant it is more active than acetylsalicylic acid, but it acts slowlier. The peak – in 3-10 days compared to 1 hour of acetylsalicylic acid. It blocks the receptors to adenosine diphosphate on thrombocytes and disturbs their binding with fibrinogen. Antiaggregant effect is achieved in 24-48 hours and reaches its maximum in 3-10 days after the beginning of the course and is maintained for more 8-10 days after withdrawal. Pharmacokinetics. Rapidly and completely absorbed in GIT, bioavailibility – 80-90%. Сmax – 2 h. Т1/2 – about 13 hours. Undergoes biotransformation in liver, excreted by kidneys.Prescription. P/o – 0,25 g х 2 times a day.Adverse reactions. GI disorders, skin allergic reactions, dizziness, sometimes jaundice. Hemorrhagic manifestations are also possible, as well as leukopenia, agranulocytosis.Contraindications. High risk of bleeding, acute course of ulcer, acute hemorrhagic stroke, hepatic diseases, pregnancy, lactation. Prescription. P/o (during meal) – 0,25 g х 2 times a day.Dosage forms. Tablets – 0,125 and 0,25 g.
Drugs affecting blood coagulation
When vitamin K is present, prothrombin is formed in liver which under the influence of prothrombin activators (in particular Xa factor) and Са2+ turns into thrombin (blood coagulation factor Iia). Thrombin is protease of blood plasma which turns soluble fibrinogen into insoluble fibrin and facilitates the formation of insoluble fibrin filaments out of fibrinogen. Antithrombin III relaxes the action of Xa factor; the activity of antithrombin III gets higher at the interaction with heparin.
Drugs decreasing blood coagulation (anticoagulants)
One differentiates:- Anticoagulants of direct action (act on coagulation factors directly in);
- Anticoagulants of indirect action (disturb the formation of prothrombin in liver).
Anticoagulants of direct action
They include: ungraded heparin, low-molecular (graded) heparins, heparinoids, antithrombin III, hirudin drugs – lepirudin, sodium citrate.
Heparin – a natural anticoagulant obtained out of tissues of animals; sulphated mucopolysaccharide; molecular weight – 15000.Pharmacodynamics. Heparin acts on co-factor of antithrombin III as well as on blood coagulation factors IXa, Xa, XIa, XIIa. The action of antithrombin III is relatively slow. Heparin forms a complex together with thrombin and antithrombin III. At the same time the action of antithrombin III on thrombin is fastened 1000 times; the activity of thrombin is being reduced, the formation of fibrin filaments is also going down. At the single i/v administration inhibition of blood coagulation starts immediately and lasts for 4-5 hours. At i/m administration – in 15-30 minutes and lasts up to 6 hours. At s/c administration – 40-60 min and lasts up to 8 hours. The antagonist of heparin is protamine sulphate.Indications:- Prevention and treatment of thrombosis of profound veins of shin;
- Thromboembolism of pulmonary artery;
- Instable angina, myocardial infarction;
- Coronary angioplasty;
- Acute thrombotic occlusion of peripheral arteries;
- Prevention of thromboformation during atrial fibrilation.
Pharmacokinetics. Bioavailibility is low if it’s administered s/c. Сmax – 2-4 h, Т1/2 – 1-2 h. Actively captured by endothelial cells and cells of mononuclear-macrophagic system. It undergoes desulphitation under the influence of N-desulphamidase and hepatinase of thrombocytes; excreted by kidneys in the form of metabolites. Prescription. For the prevention of venous thrombosis and thromboembolism one administers 5000 IU х 2-4 times a day – s/c. The action of heparin must me monitored by coagulogram. Adverse reactions. Apart from hemorrhages, the use of heparin may lead to the development of thrombocytopenia, osteoporosis, alopecia, hypoaldesteronism, hyperkalemia.Contraindications. Haemophilia, hemorrhagic diathesis, high permeability of vessels, hemorrhages of any localization, malignant tumors, ulcerations of GIT, bacterial endocarditis, derious disturbances of hepatic function, renal function, leukemia, aplastic and hypoplastic anemia, acute cardiac aneurysm, venous gangrene, allergic reactions. Dosage form. Solution of sodium salts of heparin for injections.
Low-molecular (graded) heparins
Low-molecular fragments of heparin. The size of their molecules is nearly 3 times smaller than heparin molecules (molecular weight – 5000). That is why they may not form a complex of thrombin and antithrombin III but they can only combine with antithrombin III and in this complex they reduce the activity of Xa factor. Graded heparins do not influence on the activity of thrombin. The drugs of low-molecular heparins are: dalteparin sodium, nadroparin calcium, Parnaparin sodium, Reviparin Sodium, Sulodexide, Tinzaparin sodium, Enoxaparine sodium. Next generation drug is Fondaparinux sodium.
Nadroparin calcium (Fraxiparine)
Pharmacokinetics. Administered s/c, bioavailibility – 98%. Сmax– 4-6 h, Т1/2 – 3,5 h (at the repeated administration – 8-10 h).Prescription. S/c administration (into abdominal cellular tissue) 1-2 times a day, sometimes i/v monitoring blood coagulation index. Adverse reactions. Hemorrhage and thromboctopenia, allergic reactions, rarely – hematomas in the site of administration. Contraindications. Thrombocytopenia, inclination to hemorrhages, including the ones caused by ulcer, cerebral blood circulation disorder, pregnancy. The control of thrombocytes is required. Drug interactions. Fraxiparin mustn’t be used together with antiaggregants, NSAIDs, other coagulants.Dosage forms. Solution for injections in disposable syringes.
Anticoagulants of indirect action
- Monocoumarin derivatives – Warfarine, Acenocumarol;
- Dicumarin derivatives – ethyl biscoumacetate;
- Indandion derivatives – Phenindione.
Warfarin
Pharmacodynamics. Inhibits synthesis of vitamin K-dependent blood coagulation factors (II, VII, IX, X) in liver. It is used for the prevention of thrombosis and embolism. The onset of action is in 3-5 days.Pharmacokinetics. It is completely absorbed in GIT, Т1/2 – 40 h., biotransformation – in liver, excretion – by kidneys. Prescription. P/o starting with 0,01 g (10 mg) once a day for 1-2 days. Then the dose is reduced раз controlling international normalized ratio (INR). Adverse reactions. Hemorrhages, rarely – vasculitis, diarrhea, high activity of hepatic enzymes, eczema, alopecia.Contraindications. Acute hemorrhages, serious hepatic and renal dysfunction, arterial hypertension, pregnancy, lactation.Dosage form. Tablets – 0,0025 g (2,5 mg).
Drugs affecting fibrinolysis
Pharmacodynamics. Thrombolytic action is associated with an ability to convert the circulating inactive protein plasminogen into an active enzyme plasmin which causes lysis of coagulated fibrin and disintegration of thrombus.Streptokinase – is an enzymatic drug obtained out of culture of β-hemolytic strptoccocus of group C. Indications:- Thromboembolism of pulmonary artery;
- Thrombosis and embolism of peripheral arteries;
- Thrombosis of superficial and profound veins (of limbs, pelvis);
- Acute myocardial infarction (first 12 hours.)
- Thrombosis of vessels of eye retina.
Prescription. Administration with an IV-drip, if necessary – intraarterially. Initial dose – 250000 IU in 50 ml of 0,9% NaCl solution slowly.Dosage forms. Freeze-drying powder for injection solutions in vials.Alteplase – an enzyme synthesized in tissues of mammals, It can convert plasminogen into plasmin.Pharmacodynamics. In comparison with other fibrinolytic drugs alteplase acts on thrombus more selectively, has short half-life period, doesn’t possess antigen properties that lets to use it repeatedly.Dosage forms. Freeze-drying powder for injection solutions in 0.05 g vials.
Inhibitors of fibrinolysis
( 1 ) Aminocapronic acid (Acidum aminocapronicum)
Pharmacodynamics. It blocks activators of plasminogen and partly inhibits the action of plasmin. It exerts a specific styptic action in case of hemorrhages associated with an increase of fibrinolysis. It is used for the arrest of bleeding during surgical procedures and pathological states when fibrinolytic activity of blood and tissues is high. Pharmacokinetics. It is rapidly absorbed. Сmax – 90 min., Т1/2 – 2 h. Elimination – by kidneys mainly in an unchanged form. Prescription. I/v and p/o. In case of acute hypofibrinogenemia – i/v administration, 4-5 g within an hour, monitoring coagulogram. Adverse reactions. Arterial hypotension, bradykardia, arrhythmia, dizziness, nausea, diarrhea, rhabdomyolisis, hearing impairment.Contraindications. Inclination to thrombosis and embolism, renal diseases, cerebral blood circulation disorder, DIC-syndrome, pregnancy. Dosage form. 5% solution for infusions in 100 ml vials.
( 2 ) Contrical
Pharmacodynamics. It inhibits proteolytic enzymes (tripsin, chymotrypsin, kallikrein and plasmin) in blood plasma. By inhibiting plasmin, it reduces fibrinolytic activity of blood, exerts hemostatic action in case of coagulopathy. It is used for bleeding conditioned by hyperfibrinolysis, for instance, after surgeries and traumas, during and after labor, for complications caused by thrombolytic conduction.Prescription. Stream i/v administration or with an IV-drip. One starts with the dose of 350000 IU, then – 140000 IU every 4 hours till hemostasis. Adverse reactions. Arterial hypotension, tachycardia, nausea, vomiting, allergic reactions, trombophlebitis in the administration site.Dosage forms. Powder for injection solutions in vials and ampoules.
Drugs facilitating blood coagulation
The synthesis of blood coagulation factors in liver: II (prothrombin), VII, IX, X depends on vitamin K. One differentiates vitamin К1 – phylloquinone (contained in plants), vitamin К2 – menaquinone (produced by intestinal micro flora) and vitamin К3 – menadione (precursor of vitamin К1).In medicine the drug of vitamin К1 Phytomenadion (Menadione) and watersoluble derivative of Menadione – Menadione sodium bisulfite (Vicasol) – are mainly used. These drugs promote the formation of prothrombin. They are prescribed for bleeding caused by hypoprothrombinemia in case of hypovitaminosis of К1. Phytomenadion and Menadione are also used at the overdose with indirect anticoagulants as their antagonist (Vicasol in this case is nit effective enough).
( 1 ) Vicasol
Unlike natural drugs of vitamin K (Phytomenadion etc.) Vicasol is a watersoluble compound and can be used not only p/o but parenterally as well. Prescription. P/o (in the form of tablets or water solution) and i/m. Daily dose for adults (p./o) – 0,015-0,03 g; i/m – 0,01-0,015 g. Used for 3-4 days with a break of 3-4 days. Contraindications. High blood coagulation and thromboembolism.
( 2 ) Fibrinogen
Pharmacodynamics. A blood component. The transition of fibrinogen into fibrin, possible under the influence of thrombin, provides the terminal stage of blood coagulation process – the formation of a clot. It is obtained out of blood donors’ plasma. Rarely used. Prescription. Administered into a vein with an IV-drip. Average dose – 2-4 g.Contraindications. Prethrombosis states, thrombosis of various etiology, high blood coagulation, myocardial infarction. Dosage forms. Lyophilizate for the injection solutions in 0,8-1,8 vials.
( 3 ) Thrombin (Trombinum)
A component of blood coagulation system. It is formed out of prothrombin at its enzymatic activation by thromboplastin. It is obtained out of donors’ blood plasma. Prescription. Thrombin solution is only used locally to stop the bleeding out of small capillaries and parenchymatous organs (during craniocerebral surgeries, surgeries on parenchymatous organs, bleeding out of bone cavity, gums etc). Thrombin is not used in case of bleeding out of large vessels. No i/v or i/m administration. Dosage forms. Lyophilizate for solutions for the local use in 10 ml ampoules.
Drugs increasing rhythmic contractions and tone of myometrium
This group includes the drugs of oxytocin and prostaglandins.
Oxytocin is a hormone of the posterior lobe of hypophysis.
Pharmacodynamics. It stimulates the rhythmic uterine contractions. In higher doses it increases the tone of myometrium. Nonpregnant uterus and the one in the beginning of the pregnancy are not very sensitive to the action of oxytocin. During pregnancy the sensitivity gradually becomes higher. Before the labor, during the labor and during the first day after the labor it is most prominent. In lactation period oxytocin stimulates lactation increasing the contraction of myoepithelial cells in the ducts of mammary glands. It exerts pressor and antidiuretic actions.
Prescription. I/v, i/m and intranasal administration. For the induction and stimulation of labor it is administered with an i/v drip – 1-2МЕ in 400 ml of 5% glucose or i/m – 1 or 0,5МЕ with an interval of 30-60 min. To stimulate lactation one administers it i/m or intranasally – 0,5МЕ 5 minutes before breastfeeding.
Adverse reactions. Nausea, vomiting, bradykardia, arrhythmia, arterial hypertension, fluid retention, bronchospasm, discoordinated labor, premature detachment of placenta, allergic reactions.
Contraindications. Inadequacy in sizes of fetus and pelvis, oblique or transverse lie, risk of metrorrhexis, presence of scars on uterus after previous C-section, premature labor, renal failure, arterial hypertension, cardiovascular failure.
Dosage forms. Solution for injections in 1 ml ampoules (5 or 10МЕ) and 2 ml (2МЕ).
Prostaglandin drugs
( 1 ) Dinоprost (Prostin F2a, Enzaprost-F)
Dinоprost (Prostin F2a, Enzaprost-F) is the main representative of prostaglandins used in obstetrics.
Pharmacodynamics. It possesses a prominent stimulating effect on smooth muscles of uterus (increases the tone of myometrium, relaxes the uterine cervix). Stimulation of uterine contractions is possible at any term of pregnancy unlike in case of oxytocin.
Prescription. The main administration routes for prostaglandins are: i/v, extraamnial, intraamnial, intravaginal. To induce the labor activity Dinoprost is administered by i/v drip in the dose of 0,001-0,005 g (1-5 mg) in 400 ml of 5% glucose or 0,09% solution of NaCl. Intravaginal – 0,005 g (5 mg) every 2 hours.
Adverse reactions. Nausea, vomiting, diarrhea, tachycardia, bronchospasm, allergic reactions, if administered i/v – phlebitis, fever.
Contraindications. In case of pregnancy with uterine scar, anatomical and clinically narrow pelvis, ulcerative colitis, heart failure, renal and hepatic diseases, deseases of blood formation, inclination to bronchospasm, glaucoma.
Dosage form. 0,5% solution in ampoules – 1; 5 and 8 ml.
( 2 ) Ergot and its alkaloids
It exerts a stimulating action on uterine muscles. It is used in case of uterine insufficiency and uterine bleedings. The styptic effect is conditioned by the compression of the walls of vessels when the muscles contract. It is not used for the labor speeding-up. The main drugs of this group are: Ergometrine, Methylergometrine, Ergotamine, Ergotal.
( 3 ) Ergometrine (Metriclavin)
Pharmacodynamics. It affects the uterine muscles faster and more effectively than other alkaloids, increases the tone of uterus and increasing the rate of contractions.
Prescription. P/o, i/m, i/v. Single dose for parenteral administration – 0.1-0.2 mg (0.5-1 ml of 0.02% solution), p/o - (1-2 tab) 2-3 times a day.
Adverse reactions. Nausea, vomiting, pain in the region of heart, arterial hypertension, ergotism (disturbance of tissue trophism caused by a spasm).
Contraindications. Pregnancy and labor.
Dosage forms. Tablets – 0,0002 g (0,2 mg); 0,02% solution in 0.5 and 1 ml ampoules (0,1 and 0,2 mg).
Drugs affecting the blood system
Drugs affecting erythropoiesis
The stimulators of erythropoiesis: Epoetine, Cyanocobalamine, folic acid, iron drugs.
Iron sulphate (Ferrosisulfas, Hemofer, prolonged action Ferrogradumet) is used in case of iron-deficient anemia and chronic posthemorrhagic anemia.
Prescription. P/o (after meal) for adults – 0,3-0,5 g х 3-4 times daily. Prolonged Hemofer – 1 dragee х 1-2 times a day.
Adverse reactions. Hyperthermia, skin hyperaemia, nausea, vomiting, constipation or diarrhea.
Contraindications. Hemochromatosis, aplastic, hemolytic anemia, chronic hepatic and renal diseases, chronic inflammatory diseases, leukaemia.
Dosage forms. Tablets – 0,105, 0,3 and 0,325 g. Dragee – 0,345 g and 0,325 g.
( 1 ) Co-amide
Pharmacpdynamics. Cobalt is a stimulator of blood formation. It facilitates the uptake of iron, stimulates the synthesis of hemoglobin, normalizes erythropoiesis, eliminate anemia. It used for the treatment of hypochromic, hypoplastic and other types of anemis which are resistant to iron drugs.
Prescription. Administered s/c – in the form of 1% water solution, 1 ml daily. P/o – 0,1 g x 3 times daily.
Dosage forms. 1% solution in 1 ml ampoules.
( 2 ) Cyanocobalamine, vitamin В12 (Cyanocobalaminum)
Pharmacodynamics. In the body it turns into a coenzyme – adenosylcobalamin or Cobamamide. The growth factor necessary for blood formation and maturation of erythrocytes. It activates the coagulatory blood system: increases thromboplastic activity and activity of prothrombin. It is a high-performance antianemic drug. It exerts a therapeutic effect for Addison-Biermer’s disease, agastric anemia, for anemia caused by gastric or intestinal diseases, for anemia conditioned by the invasion of broad tapeworm, pregnancy, for pernicious, posthemorrhagic, iron-deficient, aplastic anemia caused by toxic and substances and medicaments.
Prescription. I/m, i/v, intralumbar administration. In case of anemis associated with the deficiency of vitamin В12 one administers 1-0,2 mg once in 2 days; in case of Addison-Biermer’s anemia with the involvement of nervous system – 0.5 mg. Simultaneously, one prescribes folic acid.
Adverse reactions. Well-tolerated. Allergic reactions, nervous excitation, heartaches, tachycardia.
Contraindications. Thrombosis, erythremia, erythrocytosis. С With caution – in case of angina.
Drug interactions. It is not recommended to administer В1,and В6,together in one syringe because the containing cobalt ion facilitate the desintegration of other vitamins. Vitamin В12 can intensify the allergic reactions to vitamin В1.
Dosage forms. 0,003%, 0,01%; 0,02%, 0,05% and 0,1% solutions in ampoules and 1 ml vials.
( 3 ) Folic acid (Acidumfolicum, Folacin)
Pharmacodynamics. In the body it is reduced to tetrahydrofolic acid which is a coenzyme. It is necessary for the normal blood cell formation including the processes of maturation of megaloblasts and synthesis of normoblasts. At the lack of folic acid megaloblasts appear in the blood. Together with vitamin В12 it stimulates erythropoiesis, participates in the synthesis of aminoacids (methionine, serine etc.), nucleic acids, purines and pyrimidines, in the metabolism of choline.
It is used for the stimulation of erythropoiesis in case of macrocytic hyperchromic anemia, anemia caused by medications, ionizing radiation, anemia after gastrectomy, intestinal ectomy, alimentary macrocytic anemia in newborns. It is not very effective in case of aplastic anemia. It is also used for the chronic intestinal diseases.
Prescription. Adults – 0,005 g (5 mg) daily. The course – 20-30 days. For the prevention of folic deficiency at unbalanced nutrition – 0,02-0,05 mg daily.
Adverse reactions. Allergic reactions are possible.
Drug interaction. Analgesics, antoconvulsants, antacids, antibiotics, sulfanilamides and cytostatics reduce the effect of folic acid.
Dosage form. 0,001 g tablets (1 mg).
( 4 ) Epoetin alfa (Эпрекс) and Epoetin beta (Erythrostim, Recormon)recombinant drugs of human erythropoietin.
Pharmacodynamics. It stimulates mitosis and differentiation of erythroid cells-precursors, increase the number of erythrocytes as well as the level of hempglobin. It is used for anemia caused by bone marrow damage, chronic renal failure, during the treatment by Zidovudine in premature newborns.
Pharmacokinetics. At the s/c administration bioavailibility – 25%. Сmax– 12 h,Т1/2 – up to 24 hours, at i/v administration – 5-6 h.
Prescription. S/c or i/v administration (stream) at first normally 50-75 IU/kg 3 times a day.
Adverse reaction. High arterial pressure, convulsions, thrombocytosis, thrombocytopenia, thromboembolic complications, hyperkaliemia, iron-deficient states, allergic reactions etc.
Contraindications. Resistant arterial hypertension, pregnancy, lactation.
Dosage form. Solution for injections in 1 ml ampoules (500, 2000, 4000, 10000 IU).
Drugs affecting leukopoiesis
timulators of leukopoiesis: the drugs of colony-stimulating factors, sodium nucleinate. 4 colony-stimulating factors (CSF) are differentiated among biogenic stimulators of leukopoiesis: granulocytic CSF (stimulates the production of neutrophils, eosinophils, basophils), macrophage CSF (stimulates the production of monocytes that turn into macrophages in tissues), , которые в тканях превращаются в макрофаги), granulocytic-macrophage CSF, interleukin-3 (universal CSF).
( 1 ) Filgrastim (Neupogen)
Filgrastim (Neupogen) is a polypeptide obtained by genetically engineered way via Eschеrichiacoli. It contains the gen of granulocytic human CSF.
Pharmacodynamics. It stimulates granulocytopoiesis. It interacts with the receptors on the surface of hemopoietic cells, fasten the biosynthesis and release of neutrophils in the bone marrow.
Prescription. I/v and s/c administration. Doses are adjusted individually. In case of cytotoxic neutropenia one administers 500000 IU/day.
Adverse reactions. Side effects are rarely noticed. Pain in bone is possible as well as in muscles, skin redness and pain in the site of injection, allergic reactions.
Dosage forms. Solution for injections in vials, syrettes – 30 and 48 mln IU. Administration – with 5% glucose.
( 2 ) Sodium nucleinate (Natriinucleinas)
Pharmacodynamics. It is used as an immunostimulating agent in complex therapy in case of diseases accompanied by the developing immunodeficiency, leukopenia and agranulocytosis included.
Prescription. P/o (after meal) for adults a daily dose should contain1-2 g (in 3-4 intakes). The course of therapy – from 2 weeks to 3 months. The therapy is performed with the control over the immune status.
Dosage forms. Powder in 0,5 g vials for p/o use.
Drug affecting the formation of thrombus
The formation of thrombus in arterial vessels starts with aggregation of thrombocytes induced by the damage to vascular endothelium. The aggregation process is followed by coagulation process – the formation of fibrin filaments that make a thrombus firmer.
The aggregation of thrombocytes is prevented by prostacyclin (prostacyclin I2), while coagulation – by antithrombin III and heparin. The formed thrombus may be dissolved under the influence of fibrinolysin (plasmin).
Drugs affecting the formation of a thrombus are divided into:
- Drugs affecting the aggregation of thrombocytes;
- Drugs affecting blood coagulation;
- Drugs affecting fibrinolysis.
Antiaggregants prevent adhesion of thrombocytes – initial stage of thrombus formation, mainly in arterial vessels and less – in venous ones. Used for the prevention of thrombus formation.
( 1 ) Acetylsalicylic acid (Aspirin)
Acetylsalicylic acid (Aspirin) is a nonsteroid anti-inflammatory drug (NSAID). It exerts ani-inflammatory, anesthetic, anti-fever effects. For that purpose it is used in the dose 0,5-1 g/day.
Pharmacodynamics. Administered p/o it irreversibly inhibits cyclooxygenase-1 in thrombocytes and vascular endothelium disturbing the formation of aggregants: thromboxane А2 and prostacyclin.
Indications:
- Acute myocardial infarction, starting from the first hours;
- Prevention of myocardial infarction;
- Instable angina;
- After coronary angioplasty and stenting of coronary vessels;
- Cerebral blood circulation disorder by ischemic type;
- Prevention of thromboformation at the atrial fibrillation and in case of contraindications for the use of coagulants;
- intermittent claudication.
Pharmacokinetics. After ingestion it is rapidly and completely absorbed. Т1/2 is no more than 15-20 min. It easily gets into tissues. Biotransformation in the intestinal and hepatic walls with the formation of salicylic acid. Eliminated by kidneys in an unchanged form.
Prescription. Prominent reduction of aggregation is possible with the dose 75-325 mg/day. Most frequently prescribed - 0,1 g (100 mg) х once a day.
Dosage forms. Tablets – 0,1 g, 0,25, 0,5 g.
( 2 ) Clopidogrel
Pharmacodynamics. It inhibits the aggregation of thrombocytes by blocking the binding of adenosine diphosphate to the receptors of thrombocytes. Maximum antiaggregant effect is achieved in 4-7 in the therapy and is maintained up to 4-10 days.
Pharmacokinetics. Rapidly absorbed. Сmax – 1 h. Т1/2 – 8 h. Biotransformation – in liver with the formation of an active metabolite. Excreted with urine and feces.
Prescriprion. P/o – 0,075 g once a day.
Dosage forms. Tablets – 0,075 g (75 mg).
( 3 ) Ticlopedine
Pharmacodynamics. As an antiaggregant it is more active than acetylsalicylic acid, but it acts slowlier. The peak – in 3-10 days compared to 1 hour of acetylsalicylic acid. It blocks the receptors to adenosine diphosphate on thrombocytes and disturbs their binding with fibrinogen. Antiaggregant effect is achieved in 24-48 hours and reaches its maximum in 3-10 days after the beginning of the course and is maintained for more 8-10 days after withdrawal.
Pharmacokinetics. Rapidly and completely absorbed in GIT, bioavailibility – 80-90%. Сmax – 2 h. Т1/2 – about 13 hours. Undergoes biotransformation in liver, excreted by kidneys.
Prescription. P/o – 0,25 g х 2 times a day.
Adverse reactions. GI disorders, skin allergic reactions, dizziness, sometimes jaundice. Hemorrhagic manifestations are also possible, as well as leukopenia, agranulocytosis.
Contraindications. High risk of bleeding, acute course of ulcer, acute hemorrhagic stroke, hepatic diseases, pregnancy, lactation.
Prescription. P/o (during meal) – 0,25 g х 2 times a day.
Dosage forms. Tablets – 0,125 and 0,25 g.
Drugs affecting blood coagulation
When vitamin K is present, prothrombin is formed in liver which under the influence of prothrombin activators (in particular Xa factor) and Са2+ turns into thrombin (blood coagulation factor Iia). Thrombin is protease of blood plasma which turns soluble fibrinogen into insoluble fibrin and facilitates the formation of insoluble fibrin filaments out of fibrinogen. Antithrombin III relaxes the action of Xa factor; the activity of antithrombin III gets higher at the interaction with heparin.
Drugs decreasing blood coagulation (anticoagulants)
One differentiates:
- Anticoagulants of direct action (act on coagulation factors directly in);
- Anticoagulants of indirect action (disturb the formation of prothrombin in liver).
Anticoagulants of direct action
They include: ungraded heparin, low-molecular (graded) heparins, heparinoids, antithrombin III, hirudin drugs – lepirudin, sodium citrate.
Heparin – a natural anticoagulant obtained out of tissues of animals; sulphated mucopolysaccharide; molecular weight – 15000.
Pharmacodynamics. Heparin acts on co-factor of antithrombin III as well as on blood coagulation factors IXa, Xa, XIa, XIIa. The action of antithrombin III is relatively slow. Heparin forms a complex together with thrombin and antithrombin III. At the same time the action of antithrombin III on thrombin is fastened 1000 times; the activity of thrombin is being reduced, the formation of fibrin filaments is also going down. At the single i/v administration inhibition of blood coagulation starts immediately and lasts for 4-5 hours. At i/m administration – in 15-30 minutes and lasts up to 6 hours. At s/c administration – 40-60 min and lasts up to 8 hours. The antagonist of heparin is protamine sulphate.
Indications:
- Prevention and treatment of thrombosis of profound veins of shin;
- Thromboembolism of pulmonary artery;
- Instable angina, myocardial infarction;
- Coronary angioplasty;
- Acute thrombotic occlusion of peripheral arteries;
- Prevention of thromboformation during atrial fibrilation.
Pharmacokinetics. Bioavailibility is low if it’s administered s/c. Сmax – 2-4 h, Т1/2 – 1-2 h. Actively captured by endothelial cells and cells of mononuclear-macrophagic system. It undergoes desulphitation under the influence of N-desulphamidase and hepatinase of thrombocytes; excreted by kidneys in the form of metabolites.
Prescription. For the prevention of venous thrombosis and thromboembolism one administers 5000 IU х 2-4 times a day – s/c. The action of heparin must me monitored by coagulogram.
Adverse reactions. Apart from hemorrhages, the use of heparin may lead to the development of thrombocytopenia, osteoporosis, alopecia, hypoaldesteronism, hyperkalemia.
Contraindications. Haemophilia, hemorrhagic diathesis, high permeability of vessels, hemorrhages of any localization, malignant tumors, ulcerations of GIT, bacterial endocarditis, derious disturbances of hepatic function, renal function, leukemia, aplastic and hypoplastic anemia, acute cardiac aneurysm, venous gangrene, allergic reactions.
Dosage form. Solution of sodium salts of heparin for injections.
Low-molecular (graded) heparins
Low-molecular fragments of heparin. The size of their molecules is nearly 3 times smaller than heparin molecules (molecular weight – 5000). That is why they may not form a complex of thrombin and antithrombin III but they can only combine with antithrombin III and in this complex they reduce the activity of Xa factor. Graded heparins do not influence on the activity of thrombin. The drugs of low-molecular heparins are: dalteparin sodium, nadroparin calcium, Parnaparin sodium, Reviparin Sodium, Sulodexide, Tinzaparin sodium, Enoxaparine sodium. Next generation drug is Fondaparinux sodium.
Nadroparin calcium (Fraxiparine)
Pharmacokinetics. Administered s/c, bioavailibility – 98%. Сmax– 4-6 h, Т1/2 – 3,5 h (at the repeated administration – 8-10 h).
Prescription. S/c administration (into abdominal cellular tissue) 1-2 times a day, sometimes i/v monitoring blood coagulation index.
Adverse reactions. Hemorrhage and thromboctopenia, allergic reactions, rarely – hematomas in the site of administration.
Contraindications. Thrombocytopenia, inclination to hemorrhages, including the ones caused by ulcer, cerebral blood circulation disorder, pregnancy. The control of thrombocytes is required.
Drug interactions. Fraxiparin mustn’t be used together with antiaggregants, NSAIDs, other coagulants.
Dosage forms. Solution for injections in disposable syringes.
Anticoagulants of indirect action
- Monocoumarin derivatives – Warfarine, Acenocumarol;
- Dicumarin derivatives – ethyl biscoumacetate;
- Indandion derivatives – Phenindione.
Warfarin
Pharmacodynamics. Inhibits synthesis of vitamin K-dependent blood coagulation factors (II, VII, IX, X) in liver. It is used for the prevention of thrombosis and embolism. The onset of action is in 3-5 days.
Pharmacokinetics. It is completely absorbed in GIT, Т1/2 – 40 h., biotransformation – in liver, excretion – by kidneys.
Prescription. P/o starting with 0,01 g (10 mg) once a day for 1-2 days. Then the dose is reduced раз controlling international normalized ratio (INR).
Adverse reactions. Hemorrhages, rarely – vasculitis, diarrhea, high activity of hepatic enzymes, eczema, alopecia.
Contraindications. Acute hemorrhages, serious hepatic and renal dysfunction, arterial hypertension, pregnancy, lactation.
Dosage form. Tablets – 0,0025 g (2,5 mg).
Drugs affecting fibrinolysis
Pharmacodynamics. Thrombolytic action is associated with an ability to convert the circulating inactive protein plasminogen into an active enzyme plasmin which causes lysis of coagulated fibrin and disintegration of thrombus.
Streptokinase – is an enzymatic drug obtained out of culture of β-hemolytic strptoccocus of group C.
Indications:
- Thromboembolism of pulmonary artery;
- Thrombosis and embolism of peripheral arteries;
- Thrombosis of superficial and profound veins (of limbs, pelvis);
- Acute myocardial infarction (first 12 hours.)
- Thrombosis of vessels of eye retina.
Prescription. Administration with an IV-drip, if necessary – intraarterially. Initial dose – 250000 IU in 50 ml of 0,9% NaCl solution slowly.
Dosage forms. Freeze-drying powder for injection solutions in vials.
Alteplase – an enzyme synthesized in tissues of mammals, It can convert plasminogen into plasmin.
Pharmacodynamics. In comparison with other fibrinolytic drugs alteplase acts on thrombus more selectively, has short half-life period, doesn’t possess antigen properties that lets to use it repeatedly.
Dosage forms. Freeze-drying powder for injection solutions in 0.05 g vials.
Inhibitors of fibrinolysis
( 1 ) Aminocapronic acid (Acidum aminocapronicum)
Pharmacodynamics. It blocks activators of plasminogen and partly inhibits the action of plasmin. It exerts a specific styptic action in case of hemorrhages associated with an increase of fibrinolysis. It is used for the arrest of bleeding during surgical procedures and pathological states when fibrinolytic activity of blood and tissues is high.
Pharmacokinetics. It is rapidly absorbed. Сmax – 90 min., Т1/2 – 2 h. Elimination – by kidneys mainly in an unchanged form.
Prescription. I/v and p/o. In case of acute hypofibrinogenemia – i/v administration, 4-5 g within an hour, monitoring coagulogram.
Adverse reactions. Arterial hypotension, bradykardia, arrhythmia, dizziness, nausea, diarrhea, rhabdomyolisis, hearing impairment.
Contraindications. Inclination to thrombosis and embolism, renal diseases, cerebral blood circulation disorder, DIC-syndrome, pregnancy.
Dosage form. 5% solution for infusions in 100 ml vials.
( 2 ) Contrical
Pharmacodynamics. It inhibits proteolytic enzymes (tripsin, chymotrypsin, kallikrein and plasmin) in blood plasma. By inhibiting plasmin, it reduces fibrinolytic activity of blood, exerts hemostatic action in case of coagulopathy. It is used for bleeding conditioned by hyperfibrinolysis, for instance, after surgeries and traumas, during and after labor, for complications caused by thrombolytic conduction.
Prescription. Stream i/v administration or with an IV-drip. One starts with the dose of 350000 IU, then – 140000 IU every 4 hours till hemostasis.
Adverse reactions. Arterial hypotension, tachycardia, nausea, vomiting, allergic reactions, trombophlebitis in the administration site.
Dosage forms. Powder for injection solutions in vials and ampoules.
Drugs facilitating blood coagulation
The synthesis of blood coagulation factors in liver: II (prothrombin), VII, IX, X depends on vitamin K. One differentiates vitamin К1 – phylloquinone (contained in plants), vitamin К2 – menaquinone (produced by intestinal micro flora) and vitamin К3 – menadione (precursor of vitamin К1).
In medicine the drug of vitamin К1 Phytomenadion (Menadione) and watersoluble derivative of Menadione – Menadione sodium bisulfite (Vicasol) – are mainly used. These drugs promote the formation of prothrombin. They are prescribed for bleeding caused by hypoprothrombinemia in case of hypovitaminosis of К1. Phytomenadion and Menadione are also used at the overdose with indirect anticoagulants as their antagonist (Vicasol in this case is nit effective enough).
( 1 ) Vicasol
Unlike natural drugs of vitamin K (Phytomenadion etc.) Vicasol is a watersoluble compound and can be used not only p/o but parenterally as well.
Prescription. P/o (in the form of tablets or water solution) and i/m. Daily dose for adults (p./o) – 0,015-0,03 g; i/m – 0,01-0,015 g. Used for 3-4 days with a break of 3-4 days.
Contraindications. High blood coagulation and thromboembolism.
( 2 ) Fibrinogen
Pharmacodynamics. A blood component. The transition of fibrinogen into fibrin, possible under the influence of thrombin, provides the terminal stage of blood coagulation process – the formation of a clot. It is obtained out of blood donors’ plasma. Rarely used.
Prescription. Administered into a vein with an IV-drip. Average dose – 2-4 g.
Contraindications. Prethrombosis states, thrombosis of various etiology, high blood coagulation, myocardial infarction.
Dosage forms. Lyophilizate for the injection solutions in 0,8-1,8 vials.
( 3 ) Thrombin (Trombinum)
A component of blood coagulation system. It is formed out of prothrombin at its enzymatic activation by thromboplastin. It is obtained out of donors’ blood plasma.
Prescription. Thrombin solution is only used locally to stop the bleeding out of small capillaries and parenchymatous organs (during craniocerebral surgeries, surgeries on parenchymatous organs, bleeding out of bone cavity, gums etc). Thrombin is not used in case of bleeding out of large vessels. No i/v or i/m administration.
Dosage forms. Lyophilizate for solutions for the local use in 10 ml ampoules.
