LEYKOTSITOPOEZ'S STIMULATORS (Latin stimulare to drive, excite; a leukocyte[s] + Greek poiesis creation) — the pharmaceuticals applied to treatment of the leukopenias connected with disturbances actually of system of a hemopoiesis or caused by various somatic and infectious diseases.
As S. of l. use drugs of nek-ry vitamins — folic acid (see), cyanocobalamine (see), pyridoxine (see); the means strengthening synthesis nucleinic to - t — pentoxyl (see), methyluracil (see), Natrium nucleinicum and leucogenum (see); drugs of nek-ry steroid hormones — glucocorticoids, androgenic drugs; salts of lithium.
Folic to - that as S. of l. it is effective generally at leukopenias (see), developing against the background of foliyevodefitsitny anemia (see). Mechanism of development of this pathology following. A shortcoming tetragidrofoliye-howl to - you (a koenzimny form folic to - you) in a cell lead to the braking of synthesis of DNA caused by deficit of thymidylates. The last causes oppression of mitotic activity of the hemopoietic cells owing to what folic and scarce anemia and the accompanying leukopenia develops. Appointment in this case folic to - you normalize a picture of blood. Cyanocobalamine provides process of transamination and hydrogen transfer, normalizes protein synthesis and nucleinic to - t. In this regard it is effective at the leukopenia developing against the background of B12 - scarce (megaloblastichesky) anemia. Thus, cyanocobalamine and folic to - that it is possible to consider l as specific S., action to-rykh is directed to elimination of the frustration which are causative factors of development of nek-ry types of leukopenias.
Other drugs are among nonspecific S. of l., since at leukopenias of various genesis they act by the pathogenetic principle. A pyridoxine, turning into pyridoxal phosphate, participates in processes of a nitrogen metabolism (transamination, deamination and decarboxylation of amino acids, and also in transformations of tryptophane, sulfur-containing amino acids and hydroxy-amino acids). In this regard it norkhmalizut leykotsitopoez at the leukopenias caused by the different reasons. Pentoxyl also marked uracil accelerate growth and reproduction of cells of marrow, but do not influence process of their maturing. Natrium nucleinicum and leucogenum stimulate maturing of cells of marrow. The l specified by S. have the minimum ability to strengthen leykotsitopoez. They are used only at easy (tranzitorny) forms of leukopenias, to-rye usually passed spontaneously. At the expressed hypoplasia of the hemopoietic fabric and leukopenias of immune genesis these drugs are inefficient.
The stimulating influence of Prednisolonum, a deksakhmetazon and other glucocorticoids on leykotsitopoez is connected with acceleration of maturing and an exit of neutrophils from marrow in blood. The stabilizing influence of glucocorticoids on membranes of cells causes reduction of intra marrowy destruction of granulocytes (a so-called inefficient granulocytopoiesis). Glucocorticoids cause also the redistribution of the circulating neutrophils connected with movement of the last of a pool of the circulating neutrophils, marginal in a pool. Drugs of this group are highly effective at immune leukopenias. However they possess vyrazhennsh pobochnsh the action consisting in disturbance of electrolytic balance, hypostases, increase in the ABP, development of a hypopotassemia, hyperglycemia, an ulceration of a mucous membrane went. - kish. a path, osteoporosis, mental disorders, disturbance of a menstrual cycle at women, etc. The stimulating influence of androgenic drugs (testosterone, Testoenatum, etc.) on leykotsitopoez, perhaps, it is connected with their anabolic effect. Besides, they accelerate proliferation and a differentiation of polipotentny stem cells, the number of granulomonotsitarny predecessors increase. The direct stimulating impact of androgenic drugs on progenitors of a granulocytopoiesis is noted. Besides, at effect of these drugs granulomonotsitopoez, apparently, amplifies also due to increase in synthesis of a colony stimulating factor monocytes. Stage of latency in operation of androgenic drugs on leykotsitopoez makes several weeks. In this regard as S. of l. they are applied at hron. forms of leukopenias.
For stimulation of a leykotsitopoez use also salts of lithium, in particular, a lity a carbonate. Lithium increases products of neutrophils, eliminates disturbances of their migration and does not suppress their migratory ability at somatic healthy faces. Salts of lithium are highly effective at the leukopenias caused by cytostatics, a hereditary neutropenia, Felti's syndrome and also at the leukopenia developing against the background of aplastic anemia. At patients with the expressed phenomena of a leukopenia of lities increases total number of neutrophils, quantity of the circulating and marginal neutrophils, extends time of half-decay of neutrophils and their turn. The mechanism of a promoting effect of drugs of lithium on leykotsitopoez is finally not found out. It is shown that in vitro of lities increases number and stimulates growth of granulotsitarny colonies of colony-forming cells. Besides, iod influence of lithium increases products of monocytes macrophages, to-rye are the main source of a colony stimulating factor. Effect of lithium on colony-forming cells of in vitro is not found when the colony stimulating factor completely is absent or contains in optimum quantity. The listed effects of lithium connect with its oppressing influence on adenylatecyclase owing to what the intracellular maintenance of cyclic AMF decreases. Lithium strengthens proliferation of lymphocytes in response to stimulation by phytohemagglutinin, increases number of rosette-forming cells and secretion of IgM V-lymphocytes in reaction of plaque formation. Consider that lithium suppresses function of T-limfotsitov-supressorov. Side effect of drugs of lithium is shown by decrease in concentration ability of kidneys, a polydipsia, nausea, vomiting, diarrhea, a tremor, an ataxy, disturbances of a cordial rhythm, the phenomena of a hypothyroidism, increase in body weight. Drugs of lithium are contraindicated at disturbance of secretory function of kidneys, cardiovascular diseases with the phenomena of a decompensation, pregnancy and a lactation. S.'s choice l. make taking into account a pathogeny a leukopenia and features of the mechanism of effect of separate drugs of this group.
Bibliography: Diamonds B. And., etc. Leukopenias, page 32, L., 1981; And with t and m of An about in and T. S. and And l of m of elements of V. A. Leukopenias and agranulocytoses, page 151, L., 1961; Mashkov with to and y M. D. Pharmaceuticals, p.1, M., 1977; I in about r to about in with to and y L. L. Lity as a stimulator of a neytropoez, Probl. gematol. and modulation, blood, t. 27. N» 11, page 50, 1982; R about s e n t h'a 1 N. E. a. Goodwin F. To. The role of the lithium ion in medicine, Ann. Rev. Med., v. 33, p. 555, 1982.
V. P. Fiyeenko.