CHEMOTHERAPY

From Big Medical Encyclopedia

CHEMOTHERAPY { chemistry [I} +

Greek therapeia treatment) — - treatment of infectious, invasive diseases and malignant new growths by means of chemotherapeutic means, i.e. the medicinal substances which are selectively suppressing in a human body development and reproduction of causative agents of the infectious diseases or oppressing proliferation zlokachestvenno of the regenerated cells of an organism or is irreversible damaging these cells. The term «chemotherapy» designate also the field of medical science, a cut enter tasks: research of chemotherapeutic means (see), development of ways of their receiving, studying of ranges, mechanisms and conditions of action of these means on causative agents of infectious diseases and zlokachestvenno the regenerated cells, and also development of rational methods of use of the specified means.

A founder of chemotherapy

is P. Ehrlich, to-ry at the beginning of 20 century formulated its main concepts and the principles, and also received and implemented in a wedge, practice the first effective chemotherapeutic remedies (see) from among compounds of arsenic.

In historical aspect the chemotherapy of malignant tumors (see Chemotherapy of tumors) arose after chemotherapy inf. diseases and therefore at the beginning of the development was based on the nek-ry main theoretical principles of chemotherapy of infections. However at the present stage of development of medical science the chemotherapy of malignant tumors (see) and leukoses (see) is inexpedient to be identified with chemotherapy inf. diseases as between tumoral and infectious processes there are basic distinctions. In this regard the modern chemotherapy of malignant tumors and leukoses develops as one of the directions of theoretical and clinical oncology (see). For the same reason the medicines used for chemotherapy of malignant diseases usually allocate in special group of so-called antineoplastic means (see).

The term «chemotherapy», i.e. treatment by chemical substances, has conditional character as in principle any kinds of medicinal therapy are based on use of chemical substances because all pharmaceuticals represent certain chemical connections of a natural or synthetic origin. However unlike pharmacotherapy (see) mean use by chemotherapy with to lay down. the purpose only of such pharmaceuticals, action to-rykh is directed directly on activators inf. diseases and invasions, i.e. on etiol. factors of such diseases. From this point of view the chemotherapy of infectious diseases represents a method of causal medicinal treatment. Do not refer treatment of infections by means of the means exerting the mediated impact on causative agents of infectious diseases, napr, vaccines, serums and immunomodulators to chemotherapy and also by means of the medicines operating on separate links of a pathogeny of infectious diseases. Thus, the term «chemotherapy» allows to delimit accurately specific (etiotropic) therapy inf. diseases and invasions from pharmacotherapy in general that has absolute importance both in theoretical, and in the practical relation. In this regard, despite convention of the value, the term «chemotherapy» for the first time offered by P. Ehrlich at the beginning of 20 century was enshrined in the address and it continues to be used widely in modern medical literature.

Development of chemotherapy is connected with achievements of a number of medicobiological sciences, adjacent to it. So, e.g., the chemotherapy is partly connected with pharmacology (see), especially in the field of studying of pharmacokinetics (see) chemotherapeutic means since patterns of pharmacokinetics are equally applicable to any medicinal substances. However for the rest the chemotherapy is accurately delimited from pharmacology by a circle of the studied phenomena (interaction of chemotherapeutic means with microorganisms, the conditions defining this interaction, etc.) and the methods of a research corresponding to them. In addition to pharmacology, the chemotherapy relies on microbiology, parasitology, immunology, genetics, inf. pathology and some other sciences.

Philosophy of chemotherapy. At use of chemotherapeutic means it is necessary to adhere to a number of the general principles, to-rye in the majority differ from the principles of pharmacotherapy.

Because chemotherapy — the etiotropic method of treatment, one of its main principles is obligatory establishment of an etiology of a disease prior to use of chemotherapeutic means to choose the drug having the highest activity concerning the causative agent of this disease among these means. Non-compliance with this principle obviously is the reason of inefficiency of chemotherapy.

Most precisely to establish an etiology inf. diseases it is possible by allocation from the sick activator in pure growth with its subsequent identification by means of the accepted methods mikrobiol. researches. However allocation of the activator at many infections is accompanied by certain difficulties, and the mentioned methods of a research demand usually considerable expenses of time. Meanwhile the chemotherapy of the infections which are especially hard proceeding and posing a threat for life of the patient needs to be begun as it is possible in earlier terms of a disease that is important not only for the benefit of the patient, but also in the epidemiological relation. In this regard the choice of drug for chemotherapy is usually made on the basis of the nosological diagnosis since activators of the majority inf. diseases (belly and sypny typhus, cholera, plague, a malignant anthrax, syphilis, tuberculosis, etc.) in a crust, time are well-known. At polyetiological diseases (sepsis, pneumonia, purulent meningitis, etc.) the chemotherapy is begun with purpose of drugs of whenever possible wider range of the antimicrobic action extending and on probable causative agents of these diseases, and after specification of an etiology passed to treatment with drugs, to the Crimea the activator allocated from the patient is most sensitive.

Not less important principle of chemotherapy is use of each drug in such dosage, its introduction in such a way and with such intervals that in places of localization of the activator were created and the concentration of drug sufficient for suppression of life activity of the activator were constantly maintained. Data, necessary for respect for this principle (a dose, duration of circulation in blood, concentration in fabrics) establish for each drug in advance (in the course of its preclinical studying and clinical tests) and include in the instruction for its use and in the corresponding reference books.

The known complexity from the point of view of the choice of an optimum dosage and the scheme of administration of separate drugs is represented by cases of their appointment as the patient inf. diseases with the accompanying renal failure when the risk of development of toxic effects of a number of drugs owing to their cumulation in an organism is high. Antibiotics of group of penicillin (see Penicillin), aminoglycosides are among such drugs, e.g., (see Antibiotics, t. 10, additional materials), cephalosporins (see), tetracyclines (see), for isklyucheniyekhm doxycycline, Amphotericinum In (see Amphotericinums), etc. Schemes of use of such drugs at a renal failure demand correction. For this purpose usually use the corresponding recommendations, to-rye, as a rule, are available in application instructions of drugs as such recommendations are usually developed even in process a wedge, approbations of drugs. Nek-ry drugs, napr, doxycycline (see Tetracyclines), levomycetinum (see) erythromycin (see IAC-rolidy), rifampicin (see Rifamycinums), etc., is not kumulirut in an organism at a renal failure in this connection at this pathology they are applied according to usual schemes.

At respect for the principle stated above concerning a dosage and schemes of use of drugs, the chemotherapy of a number of infections allows to stop acute displays of a disease very quickly. So, purpose of antimalarial means (see) from group of gematoshizotropny drugs, napr, chloroquine, immediately after the next attack of fever can lead to complete cessation of these attacks further, and a rational antibioticotherapia of nek-ry infections, napr, a lung fever, allows to stop acute displays of this disease during 1 — 2 days though full treatment demands more long complex treatment.

Many of the principles of a dosage and schemes of purpose of drugs used in pharmacotherapy, napr, purpose of drugs in small (fractional) doses, incidental use of drugs for symptomatic therapy, etc., are unacceptable in chemotherapy since at the same time one of the main conditions of efficiency of chemotherapeutic means — constant intake of drugs to places of localization of the activator in the concentration providing suppression of its life activity is broken.

Disturbance of the specified principle at chemotherapy is one of the reasons of development of medicinal stability of microorganisms (see). Depending on the frequency of detection of resistance to chemotherapeutic means all microorganisms can be divided into two groups conditionally: the first group — causative agents of infections, sensitivity to-rykh to drugs significantly does not change in the course of chemotherapy (streptococci of group A, pneumococci, meningokokk, brucellas, the causative agent of a typhoid, etc.); in that - paradise group — microorganisms (staphylococcus, gonokokk, colibacillus, klebsiyella, mycobacteria, a plasmodium of malaria, etc.), among ^рых allocate a large number of strains, steady against chemotherapeutic means (e.g., gonokokk — to streptocides, stafilokokk — to drugs of a benzylpenalty fee-tsillina, plasmodiums of malaria — to chloroquine etc.). Rather bystry development of medicinal stability in the course of chemotherapy is characteristic of activators of this group.

It is also necessary to mean that the speed of development of medicinal stability to different chemotherapeutic drugs is not identical even at the same type of activators. So, resistance of stafilokokk to antibiotics of group of macroleads (Oleandomycinum, erythromycin) and to Rifamycinums develops much quicker, than to tetracyclines and levomycetinum. Due to the possible development of medicinal stability of activators it is reasonable to define, whenever possible, their sensitivity to chemotherapeutic drugs not only before, but also in the course of chemotherapy (especially at long courses of treatment). However sometimes full coincidence of results of researches of sensitivity of the allocated activator to the drugs in vitro and their wedge, is not observed by efficiency. It is caused by the fact that in the conditions of a macroorganism accessory factors, napr, permeability of a gistogematichesky barrier (see Barjerny functions) for drugs, intensity of metabolic processes, existence in fabrics of strains of the activators having different sensitivity to drugs, etc. affect interaction of drugs with the activator.

In case of development in the course of chemotherapy of resistance of the activator to the used drug there is a need for its replacement with other drug, this activator is still sensitive to Krom. Replacement of medicine is made taking into account a possibility of so-called cross stability of the activator, edges it is shown usually not only to the used drug, but also to others similar to it on a structure and action to means. E.g., tetracycline resistance is followed by stability to all other drugs of group of tetracycline, resistance to any of streptocides — to all streptocides and t - D. -

Klien. assessment of efficiency of chemotherapy always represents the known complexity. At use bakteritsidno of the operating drugs the therapeutic effect is shown, as a rule, very quickly (during 1 — 2 days). However at seriously ill patients it is impossible to judge lack of effect 3 earlier — the 4th day from the beginning of chemotherapy. Bacteriostatic drugs render clinically expressed effect usually on 2 — the 5th day from the beginning of chemotherapy.

At the same time in itself the wedge, improvement cannot be considered as the basis to the immediate termination of chemotherapy as at the same time in an organism of the patient separate populations of viable activators can remain (especially in the centers, hardly accessible for drugs). Thus, in the course of chemotherapy determination of optimum duration of use of drugs very is important. Most just the matter is resolved when recurrence of development of the activator in a human body is strictly certain. So, at malaria processes of a schizogony of activators in erythrocytes continue at R. of vivax, P. ovale and P. falciparum of 48 hours, and at P. malariae — 72 hours what approach of attacks of fever through the corresponding time slices is connected with. Therefore at uncomplicated malaria its treatment by means of gematoshizotropny drugs (chloroquine, plaquenil) is carried out usually within 3 days. Only if necessary (at tropical malaria) duration of treatment by these drugs sometimes is increased up to 5 days. In cases when such pattern in development of the activator is absent, the optimum duration of treatment is established individually, being guided by the character of the activator, its localization, features of disease, a wedge given about efficiency of chemotherapy etc. The long chemotherapy on condition of its rational carrying out can

sometimes have diagnostic value depending on its result. So, efficiency of chemotherapy it is long in the fever patients with bactericidal antibiotics of a broad spectrum of activity testifies about infectious (most often septic) the nature of a disease. Inefficiency of an antibioticotherapia in such cases is diagnostic criterion for recognition of the noninfectious diseases proceeding with fever, napr, kollagenoz, a lymphogranulomatosis, cancer.

For increase in efficiency of treatment of infections, and also for overcoming and the prevention of medicinal stability of activators the so-called combined chemotherapy can be used, edges it is carried out by simultaneous use of two or three chemotherapeutic drugs with different mechanisms of action. For these purposes it is possible to use only those drugs, to-rye work for the activator synergistically. The combined chemotherapy found broad application at treatment of tuberculosis (see), sepsis (see), drug resistant forms of malaria (see) and some other inf. diseases. Need for the combined chemotherapy arises also when the available drugs affect not all of generation of the activator in an organism.

At a combination of nek-ry drugs antagonism on action on causative agents of infections (e.g. is observed, at use of penicillin with tetracyclines) or there is strengthening of side effects (e.g., strengthening of ototoxicity of streptomycin under the influence of a flori-mitsin, Kanamycinum). Such combinations are considered as incompatible (see Incompatibility of pharmaceuticals) and during the carrying out chemotherapy they should be avoided.

At purpose of chemotherapeutic means it is reasonable to take into account also the principles concerning use of any medicines, napr to consider a possibility of development of certain side effects, existence of genetically caused hypersensitivity to drugs (see the Idiosyncrasy) etc.

The fundamental principle of domestic medicine — to treat not a disease, and the patient extends to treatment of infectious patients. According to this principle the chemotherapy should be supplemented with other measures (leaving, a diet, use of means of pathogenetic and symptomatic therapy, etc.) promoting recovery of the patient.

The chemotherapy of malignant tumors is described in articles of the Tumour, treatment (see); Antineoplastic means (see), Chemotherapy of tumors (see).

Bibliography: Gracheva H. M and Shchetinina I. N. Clinical chemotherapy at infectious diseases, L., 1980; To and with with both r with to and y I. A. Sketches of rational chemotherapy, M., 1951;

N and in and sh both N S. M. and F and on I. P.

Rational antibioticotherapia, M., 1982; The Guide to infectious diseases, under the editorship of V. I. Pokrovsky and K. M. Loban, M., 1977; Rukovodstvo on intestinal infections, under the editorship of I. K. Moussa-bayeva, Tashkent, 1980; Ehrlich P. Materials to the doctrine about chemotherapy, the lane with it., SPb., 1911; D and with h J. Page of Antiviral agents, Ann. Rep. Med. Chem., v. 15, p. 149, 1980, bibliogr.; Infektolo-gie, hrsg. v. H. W. Ocklitz u. a., B., 1978; Manson’s tropical diseases, ed. dy Ch. Wilcocks a. P. E. C. Manson-Bahr, Baltimore, 1 972.

V. I. Pokrovsky, V. K. Muratov.

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