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Chemotherapeutic drugs - Practical hematology of children's age

Table of contents
Practical hematology of children's age
Embryonal hemopoiesis
Morfofunktsionalny characteristic of cells of marrow and peripheral blood
Marrow parenchyma cells
Peripheral blood of children of different age
The system of a hemostasis is normal
Etiology and pathogeny of leukoses
Acute leukoses
Acute leukoses - a preleukosis
Possibilities of a predictive assessment of a course of an acute lymphoblastoid leukosis at children
General principles of treatment of an acute leukosis
Chemotherapeutic drugs
Treatment of an acute lymphoblastoid leukosis
Treatment of myeloid forms of an acute leukosis
Infectious complications and symptomatic therapy of an acute leukosis
Consolidation and maintenance therapy of an acute leukosis
Immunotherapy
Remission and recurrence of an acute leukosis
Inborn leukosis
Neuroleukosis
Myelosis
Lymphogranulomatosis
Gematosarkoma
Macrofollicular lymphoma
Angioimmunoblastny lymphadenopathy
Leukemoid tests
Infectious lymphocytosis
Infectious mononucleosis
Leukemoid tests of different types
Dysfunctions of granulocytes
Leukopenias
Histiocytoses
Histiocytoses - an eosinophilic granuloma
Malignant histiocytosis
Family erythrophagocytal histiocytosis
Accumulation diseases
Nimann's illness — Peak
Angiopathies
Hemorrhagic vasculitis (Shenleyn's illness — Genokh)
Mayokki's purpura
Ataxy teleangiectasia
Entsefalotrigeminalny angiomatosis
Kortiko-meningealny diffusion angiomatosis
Cerebroretinal angiomatosis
Hypertrophic gemangiektaziya
Multiple and huge hemangiomas
Elastic fibrodisplaziya
Coagulopathies
Hereditary coagulopathies
Hemophilia And
Clinic of hemophilia
Treatment of hemophilia
Angiohemophilia
Cristmas disease (Kristmas's illness)
Hereditary deficit of factors of XI, XII, XIII and I
Dysfibrinogenemias
Hereditary deficit of factors of VII, X, V and II
Deficit K-vitaminozavisimykh of factors of coagulation
Syndrome of the disseminated intravascular coagulation
Clinic and diagnosis of the IDCS
Treatment of the IDCS
Thrombocytopenia
Idiopathic Werlhof's disease
Clinic and diagnosis of an idiopathic Werlhof's disease
Treatment of an idiopathic Werlhof's disease
Isoimmune Werlhof's disease
Transimmune Werlhof's disease of newborns
Trombogemolitichesky Werlhof's disease (syndrome Moshkovich)
Hereditary Werlhof's diseases
Trobotsitopatiya
Anemias
The anemias connected with blood loss
Chronic posthemorrhagic anemia
Iron deficiency anemias
Clinic and diagnosis of an iron deficiency anemia
Treatment of iron deficiency anemias
Sideroakhrestichesky, sideroblastny anemias
Megaloblastny anemias
Foliyevodefitsitny anemia
Hereditary forms of megaloblastny anemias
Hereditary dizeritropoetichesky anemias
The anemias connected with oppression of proliferation of cells of marrow
Hereditary hypoplastic anemias
Hemolitic anemias
Hemolitic anemias - an ovalocytosis, a hereditary stomatocytosis
Acanthocytosis, piknotsitoz
The hereditary hemolitic anemias connected with disturbance of activity of enzymes of erythrocytes
The hereditary hemolitic anemias connected with disturbance of structure or synthesis of hemoglobin
The acquired immune hemolitic anemias
Isoimmune hemolitic anemias
Treatment of a hemolitic illness of newborns
Autoimmune hemolitic anemias
List of references

Antimetabolites — synthetic antineoplastic drugs. On the structure antimetabolites have similarity to intermediate products of an exchange, coenzymes that allows them to join in a cell metabolism. However antimetabolites, being inhibitors of metabolic processes, lead to disturbance of synthesis of nucleic acids, and, respectively, to death of a cell.
6-Mercaptopurinum (Purinetholum) slows down synthesis of nucleic acids (DNA), being an antagonist of a purine exchange, and interferes with transformation of hypoxanthine into xanthine. Enters the majority of programs of treatment of an acute lymphoblastoid leukosis. 6 Mercaptopurinum tsiklospetsifichen, affect a S-phase (the period of synthesis of DNA). Drug possesses rather small toxicity, is well transferred by patients. Deep oppression of a hemopoiesis, as a rule, is not observed though therapy by 6 Mercaptopurinum, as well as all cytostatic means, has to be carried out under strict control of blood tests.
At decrease in quantity of leukocytes to 1X109/l drug cancel, treatment can be resumed at quantity of leukocytes over 2ò109/l. By-effects: damage of a mucous membrane of a digestive tract, stomatitis, dispepsichesky frustration, toxic defeat of a parenchyma of a liver with the hepatitis phenomena, a renal failure (azotemia) as a result of a hyperuricemia. Therefore extra care needs to be observed, appointing drug to the children having diseases of a liver and kidneys.
6-Mercaptopurinum is let out in tablets on 50 mg. Appoint inside. The daily dose can be given in one or two receptions, are better in the second half of day.
Methotrexate (Amethopterinum) — structural analog and the antagonist of folic acid. Drug brakes activity of enzyme of a folatreduktaza and interferes with transformation of folic acid in tetrahydrofolic and consequently, synthesis of purines and pyrimidines oppresses, that is finally — synthesis of DNA is suppressed. Drug tsiklospetsifichen, selectively affects a phase of synthesis of DNA (the S-period of a mitotic cycle of cells). It is effective at treatment of acute leukoses, it is applied in a combination with other cytostatic drugs. The methotrexate is toxic, the haemo cytopoiesis oppresses, promoting development of a leukopenia and thrombocytopenia Treatment needs to be carried out on condition of careful kliniko-hematologic control. The indication to cancellation of a methotrexate is the quantity of leukocytes lower than 1,5ò109/l. At intake the ulceration of mucous membranes of a digestive tract, an abdominal syndrome are observed. Therefore it is desirable for children to administer the drug parenterally. At treatment the methotrexate observes such complications: loss of appetite, nausea, vomiting, allergic manifestations, skin itch, toxic damage of a liver, damage of an urinary system. Drug is contraindicated in the presence of diseases of a liver and kidneys.
The methotrexate is highly effective at a neuroleukosis, but as it does not get through a blood-brain barrier, it is entered endolyumbalno. At the same time the headache, spasms can be noted.
The methotrexate is let out in tablets on 2,5 mg and in bottles on 5 mg. Contents of a bottle are dissolved in the distilled water, entered intramusculary or intravenously. It is proved that fractional introduction of a methotrexate strengthens toxic effect. Therefore the daily dose is entered in one step. Cytotoxic action of a methotrexate removes an antidote leykovorin which needs to be applied in the first 4 h after introduction of a methotrexate.
Tsitozin-arabinozid (Cytosarum, aleksan) — a synthetic antimetabolite, blocks synthesis of DNA, inhibits a DNA polymerase, interfering with transformation of cytidine in dezoksitsitidin. Drug tsiklospetsifichen, affects a S-phase of a cellular cycle. It is most effective at treatment of an acute miyeloblastny leukosis, especially in a combination with rubomitsiny. Depresses a hemopoiesis, causing a leukopenia, thrombocytopenia. Use of Cytosarum can lead to megaloblastichesky change of a hemopoiesis, however it is not an occasion to drug withdrawal. By-effects: nausea, vomiting, dispepsichesky frustration, hyperthermia. Abnormal liver functions are possible.
Tsitozin-arabinozid is effective at prevention and treatment of a neuroleukosis. In these cases it is entered endolyumbalno.
Drug is let out in bottles on 40 — 100 mg and 500 mg. Contents of a bottle are dissolved in special solvent. Enter on isotonic solution of sodium of chloride (100 — 200 ml) intravenously kapelno or struyno. The daily dose is divided into 3 receptions.
The alkylating connections. The alkylating drugs react with chemoceptors of cells and interfere with synthesis of nucleic acids at all stages of a mitotic cycle. Alkylating agents more break synthesis of DNA and to a lesser extent — synthesis of RNA, thereby having lethal effect on a cell.
Cyclophosphanum (endoksan, cyclophosphamide, Cytoxanum) — the highly active antineoplastic drug possessing a broad spectrum of activity. Cyclophosphanum is applied in various schemes of therapy of acute lymphoblastoid and miyeloblastny leukoses, a lymphogranulomatosis, lymphosarcomas and solid tumors. Circulating in blood in the connected state, drug maloaktiven, but at penetration into tumor cells it quickly collapses under the influence of the phosphatases which are contained in them and turns into an active form. Thus, it can be considered as the connection with "transport" function delivering active agent in tumor cells. Cyclophosphanum belongs to not cyclospecific connections and affects all phases of a mitotic cycle of cells, including a phase of "rest". Has rather soft effect on a hemopoiesis, practically without oppressing a thrombocytopoiesis, but influences on leykotsitopoez. The leukopenia at treatment by Cyclophosphanum is, as a rule, insignificant also quickly passing. Treatment by Cyclophosphanum is stopped at decrease in quantity of leukocytes to 2,5ò109/l and renewed at the level more ZH109/l. The most frequent by-effect — a hair loss. But the alopecia is temporary and after the termination of a course of treatment hair grow again. Nausea, vomiting which can be removed antiemetichesky means can be collateral manifestations. At treatment by Cyclophosphanum aseptic hemorrhagic cystitis with the dysuric phenomena and a hamaturia can develop. In these cases drug needs to be cancelled, carried out treatment of cystitis by the general rules. For the purpose of prevention of cystitis the children receiving Cyclophosphanum need plentiful drink. Development of toxic hepatitis can be rare complication.
Cyclophosphanum is let out in tablets on 50 mg and in bottles on 200 mg. Parenteral administration is optimum (intramusculary, intravenously). Before introduction drug is dissolved in isotonic solution of sodium of chloride at the rate of 200 mg in 10 ml.
Antineoplastic antibiotics. From group of antineoplastic antibiotics at treatment of an acute leukosis drugs of an anthracycline row are most active. Treats them rubomitsin (daunomitsin, Rubidomycinum). In the USSR rubomitsin receive from culture of a radiant mushroom of Actinomyces coeruleorubidus. Lethal effect of drug on cells is implemented by means of suppression of matrix activity of DNA in systems of a DNA polymerase and DNA-dependent RNA polymerase. Rubomitsin — not cyclospecific drug, affects the phases Gi, G2, S and a phase of "rest" Go; it is effective at treatment of acute lymphoblastoid and miyeloblastny leukoses. Possesses a wide antineoplastic action spectrum and it can be used at development of resistance to other cytostatic drugs. A hemopoiesis with preferential suppression of a myeloid sprout oppresses. At a rubomitsin the effect of "after-effect" as a result of which the number of leukocytes can decrease for several days after drug withdrawal is expressed. Rubomitsin possesses the expressed cardiotoxic action, leads to dysfunctions of a digestive tract. Allergic reactions are possible. At hit in a hypodermic basis there are an inflammation and a necrosis of fabrics therefore rubomitsin it is necessary to enter strictly intravenously. Is issued in bottles on 20 mg. Before introduction drug should be dissolved in isotonic solution of sodium of chloride at the rate of 20 mg in 10 ml.
Fermental drugs. L-A of a sparaginaz (Crasnitinum) — the fermental drug possessing antineoplastic activity. It is established that synthesis of asparagine in leukemic cells is broken as a result of decrease of the activity asparagine-sintetazy. Tumor cells need the increased delivery by blood of ready asparagine. L-asparaginase due to eliminating of amide group destroys asparagine, reducing its level. Selective destruction of biochemical defective leukemic cells results. L-asparaginase — not cyclospecific drug, affects the phase Gi, S, calls the block in the Gi/S-periods. Range of antineoplastic action is narrow, the best effect is gained at treatment of an acute lymphoblastoid leukosis at children. L-Acnapaginaza is transferred not by all patients and can give giperergichesky reactions of allergic type up to development of an acute anaphylaxis. Therefore before an initiation of treatment it is recommended to carry out test on individual sensitivity. Drug does not exert the expressed impact on a haemo cytopoiesis and can be appointed in cases when because of a hypoplasia of a marrowy hemopoiesis use of other cytostatic means is impossible. Purpose of L-asparaginase is justified at development of resistance to other chemotherapeutic means. Except allergic reactions, drug toxic affects a liver, kidneys. Can cause acute pancreatitis, defeat of the central nervous system, psychoses, a hyperthermia.
L-asparaginase is let out in bottles on 10 000 PIECES. It is removed intravenously kapelno in isotonic solution of sodium of chloride.
Alkaloids. At treatment of an acute leukosis drugs of a plant origin are used. Vincristinum and vinblastine belong to the alkaloids received from a periwinkle pink. Despite similarity of chemical structure, drugs are various on a range of antineoplastic action and toxicity. In therapy of acute leukoses Vincristinum is more effective. Vincristinum (Oncovinum) possesses antimitotic activity. Together with vinblastine it is the only drug operating on a mitosis phase. Vincristinum selectively blocks a mitosis in a metaphase stage, detaining growth of tumor cells. It is used in a combination with other drugs in the majority of programs of treatment of an acute leukosis. Vincristinum netsiklospetsifichen — affects a phase M in small doses, in high doses also affects the phases Gi, S and a phase of "rest" Go. However because of high toxicity drug cannot be used in high doses. In therapeutic doses does not exert the oppressing impact on a haemo cytopoiesis therefore such complications as a leukopenia and thrombocytopenia, meet seldom. Collateral manifestations — neuralgic pain, paresthesia, a polyneuritis, an areflexia, paralysis, an ataxy, paresis of guts are caused by a high neurotoxicity of drug. Also the alopecia having reversible character is observed.
Let out 0,5 mg in bottles. Vincristinum is entered strictly intravenously, at hit under skin inflammations and a necrosis are possible.
Vinblastine on the mechanism of action is similar to Vincristinum — blocks a mitosis in a metaphase stage. Is more effective at treatment of a lymphogranulomatosis, lympho-and reticulosarcomas. As choice drug at treatment of acute leukoses should be used in comprehensive programs only in the absence of Vincristinum. Toxic effect of vinblastine is softer, than Vincristinum. Gives similar collateral manifestations, but they

are less expressed and meet less often. At vinblastine toxic action is shown in oppression of a haemo cytopoiesis. Let out 5 mg in bottles, before introduction dissolve in isotonic solution of sodium of chloride. Enter intravenously.
Hormonal drugs. Broad application in therapy of acute leukoses was found by glucocorticosteroids. So far the mechanism of effect of hormonal drugs concerning malignant cells remains is insufficiently clear. It is established that they slow down proliferation processes mainly in lymphoid cells. Glucocorticoid drugs favorably influence processes of maturing of normal cellular elements of a haemo cytopoiesis that is especially important at development of a tsitopenichesky syndrome. The isolated use of corticosteroids gives a certain clinical effect, but at the present stage they are used as one of components of various programs of polychemotherapy.
Monotherapy by glucocorticoid hormones is justified at a deep pantsntopeniya and during the terminal period of an acute leukosis. Nonspecific action on a mitotic cycle of cells is characteristic of hormonal drugs, that is they are netsiklospetsifichna. Influence the phase Go of a mitotic cycle, causing a lysis of leukemic cells, call the block in the Gi/S-periods.
In treatment of acute leukoses, except cytostatic effect, other properties of corticosteroid drugs matter: influence on cellular membranes, reduction of vascular permeability, haemo static effect, disintoxication action.
Collateral shows of corticosteroid drugs are well studied. They are caused by immunodepressive properties that can lead to development of infectious and is purulent - septic diseases. Therefore long hormonal therapy has to be carried out under protection of antibiotics.
Strengthening catabolic processes, glucocorticosteroids lead to disturbance of different types of an exchange: water-salt (hypopotassemia), fatty, to increase of level of sugar in blood. Development of a syndrome of Kushinga, cankers of mucous membranes of a digestive tract is possible.
During treatment corticosteroid hormones recommend restriction of sodium of chloride and increase in salts of potassium and proteic matters. At long and massive therapy it is reasonable to use a discontinuous method of treatment.
Prednisolonum — synthetic drug, usually apply inside, more rare intramusculary and intravenously. Let out in tablets 5 mg and bottles on 30 mg.
Triamcinolonum (Polcortolonum, Kenacortum) is slightly more active than Prednisolonum, does not cause a delay of sodium of chloride and water in an organism, does not break potassium balance. Let out 4 mg in tablets (it corresponds 1 tablet — 5 mg of Prednisolonum).
Dexamethasone (Dexasonum) — on the properties is 7 times more active than Prednisolonum. Does not cause a delay of water and sodium of chloride in an organism. Apply inside, intramusculary, intravenously.

Fig. 10. The nomogram for definition of a body surface
Let out in tablets 0,5 mg and in bottles on 4 mg. 1 mg of dexamethasone corresponds to 7 mg of Prednisolonum. When calculating a dose of drugs the body surface is determined by the nomogram (fig. 10).



 
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