TACHYPHYLAXIS (Greek tachys bystry, fast + phylaxis protection, protection) — the phenomenon of short-term decrease in sensitivity to this or that substance providing bystry protection of an organism against various toxic influences.
The term «tachyphylaxis» was offered in 1911. E. Gley and Shampi (Ch. Champy), to-rye showed that introduction to blood an experimental animal (dogs and rabbits) of toxic extracts from a yellow body of ovaries of cows in a nonlethal dose in 15 min. protects these animals from death at introduction of lethal doses of such extracts. Later phenomenon of T. observed at experimental animals in relation to alien (bull) blood serum, and also to many other products of an animal, plant and microbic origin (ovalbumin, poison of a gyurza, dextrans, alkaloids and other toxic agents). T. note at effect of the substances having properties of gis-taminliberator — drug 48/80 (the condensed and-metoksifenil-ethylmethylamine), polyvinylpirrolidone, the twin-20, etc. T. protects animals in an experiment from so-called allergoidny reactions. These reactions differ from true allergic reactions (see. Allergy ) absence in their development of an immunological phase or reaction antigen — an antibody (see. Antigen — an antibody reaction ). Allergoidny reactions are shown by a fluid lungs, skin or mucous membranes. There are also local or generalized hemorrhages or hemorrhages like a Werlhof's disease (see). Release of a histamine, bradikinin and other mediators of the allergic reactions (see) causing increase in permeability of walls of blood vessels, edematization and hemorrhages is the cornerstone of development of allergoidny reactions. T. it can be reproduced on the isolated bodies and single cells. Mechanisms T. it is possible to explain with blockade of specific, including and toxic effect of substances (pharmaceuticals, foreign proteins, etc.) on an organism of the recipient and exhaustion of stocks of mediators of allergic reactions. In the blood of substance causing T., connect to mediators of allergic reactions, napr, foreign proteins can connect the histamine which came to a blood stream. In fabrics of substance, possessing takhifilaksichesky action, block specific receptors of a histamine and other mediators (and it is possible, and the corresponding perceiving receptors') and prevent thus implementation of toxic effect of these substances entered in high doses. It is possible to consider that reactions of T. in nek-ry cases are closed with a so-called immunological paralysis and other forms of unresponsiveness (see unresponsiveness). However completely it is impossible to identify these phenomena with each other. One of important points of application of takhi-filaktichesky effect of substances in an organism of the recipient is century of N of page and, in particular, its parasympathetic department. So, T. to bull serum did not arise at animals after bilateral section or total novocainic block of a vagus nerve on a neck. As a result resistance to primary effect of serum decreased. Efficiency of T. it was completely recovered after adequate electrostimulation central (but not peripheral) a piece of one of the cut branches of a vagus nerve or after cancellation of novocainic blockade. The hypophysectomy caused falloff of ability of an organism to T.
In the conditions of development of a number of allergic reactions of T. it is not shown. However after transferring of an acute anaphylaxis (see) develops so-called antnanafilaksnya, representing itself a condition of desensitization (see). Earlier private expression of T. considered antp-allergic immunity, under the Crimea understood decrease in sensitivity to allergen in connection with turning on of the immune mechanisms blocking allergen. Now this term is not used, it is replaced with the concept «giposensibn-lization».
Special case of T. the kind of accustoming to pharmaceuticals (see) which is characterized by a bystry anesthesia of cells to certain medicines is. Such T. observe at repeated influences of small doses and single use of high doses of medicinal substances.
Lack of diuretic effect of repeated use of Diacarbum (see) appointed in 8 — 16 hours after the first reception is caused by exhaustion of alkaline reserves of blood (see Acid-base equilibrium). Pressor effect of ephedrine (see) or tyramine (see), as well as the reductions of the isolated strip caused by them from a wall of an aorta of a rabbit, are not reproduced after several influences owing to exhaustion of stocks of holes of adrenaline (see) — a mediator of postganglionic sympathetic nervous impulses (see Mediators). Replenishment of stocks of a mediator in nerve terminations by introduction of noradrenaline to an animal or an incubation of a strip of an aorta in solution of noradrenaline eliminates T. to ephedrine as well as to tyramine. Reductions of the isolated piece of a gut of a Guinea pig under the influence of Vas12 barium chloride result from replacement of ions of Sa2 + from cytoplasmic membranes of smooth muscle cells. Exhaustion of stocks of ions of Sa2 + in membranes at repeated impacts on drug barium chloride is followed by development of T. to ions of Va2 + and to other substances (e.g., to serotonin), spazmogenny action to-rykh on unstriated muscles is implemented by means of release from membranes of ions of Sa2 + (so-called cross T.).
T. can result from conformational changes (see. Conformation ) in receptor proteins of a cell under the influence of the endogenous and exogenous substances contacting them that blocks a possibility of linkng with these receptors of substances agonists (see below). Thus the target cell temporarily loses sensitivity to a certain substance. In this case cross T. develops to substances agonists only one pharmakol. groups. E.g., the isolated trachea of a rat subjected within 30 min. to influence of Isoproterenolum (Isadrinum) in concentration of 2 - 10-4 M loses sensitivity to beta-adrenergic agonists — Isadrinum, an izoetarin, a terbutalpn, adrenaline, but not to nitrites, an Euphyllinum and other bronchial spasmolytics.
T. is the frequent reason of inefficiency of medicinal therapy. For the purpose of prevention of emergence of T. as complications of drug treatment are necessary strict observance of intervals between receptions of pharmaceuticals, rather long breaks between courses of treatment and periodic replacement of medicines by others having similar therapeutic effect, but other mechanism of action.
Bibliography: Kurygin G. V. About influence of functions of a hypophysis on development of hemotransfusionic shock with an acute fluid lungs and tachyphylaxes, in book: Vopr. morphology and patol. serd. - vascular system, under the editorship of A. K. Shipov, page 132, Yaroslavl, 1963; To at r y and G. V.'s N and B and r-with to and y R. L. Influence of a hypophysectomy and replaceable introduction of AKTG on development of gomotransfuzionny Shona with an acute fluid lungs and tachyphylaxes, Probl. endocrinins, and gormonoter., t. 10, No. 2, page 62, 1964; P about l at sh to and B. V. Takhifilak-siya's N, Wuxi. sovr. biol., t. 50, century 3(6), page 349, 1960; L about I. M. Desensiti-zation's HIV and mechanisms of its development, Pharm. and toksikol., t. 34, No. 6, page 736, 1971; With h and I rub Ch. et Gley E. Sur la toxicite des extraits de corps jaune, immunisation rapide consecutive a 1’injection de petites doses de ces extraits (tachyphylaxie), C. R. Soc. Biol. (Paris), t. 51, p. 159, 1911; S with h e 1 e r W. Grundlagen der allgemei-nen Pharmakologie, Stuttgart, 1980.
A. D. Ado, I. V. Komissarov.