CUMULATION (Latin cumulatio increase, accumulation) — accumulation of biologically active agent (material To.) or the effects caused by it (functional To.) at repeated influences of medicinal substances and poisons.
Material cumulation it is inherent to substances which are slowly removed and (or) are slowly inactivated in an organism. At the same time the amount of the substance entered repeatedly is summed up with that its quantity, a cut remained in an organism from the previous introduction; the total operating dose increases that leads to strengthening of effect of substance. Accumulation of substance in an organism in the course of material To. to the level of toxic doses leads to development intoxications (see). Almost in all cases when the speed of intake of substance in an organism (high doses, frequent receptions) during rather long time appears higher than the speed of its biotransformation and removal from an organism, it is necessary to expect cumulative action of this substance. Material To. it is characteristic of some heavy metals (mercury), rare-earth and radioelements (iridium, plutonium), many alkaloids (atropine, strychnine), a number of cardiac glycosides (drugs of a foxglove, etc.), hypnagogues (barbital, phenobarbital), anticoagulants (Dicumarinum), streptocides of long action (sulfadimethoxine), etc. Small speed of allocation and an inactivation of such substances finds quantitative expression in high sizes of «time (t)) of action» or «gemikreza» — time of disappearance from blood of a half of the entered substance (T 50 ). As the speed of removal and neutralization of medicinal substances is not a constant, and can decrease considerably at pathology of a liver or kidneys, probability material To. increases at diseases of these bodies. To. medicinal substances it is usually undesirable. However in some cases, napr, at purpose of drugs of a foxglove (see. Foxglove ) or anticoagulants of indirect action (Dicumarinum, neodicoumarin, etc.), this phenomenon is used for obtaining in a short space of time the maximum therapeutic effect. Thanks to ability of the specified means to material To. it is possible to support stable therapeutic effect for a long time, regulating the size of a daily dose.
Functional cumulation it is proved experimentally for drugs of lead at which long influence cats perish at the phenomena of bulbar paralysis, despite the lack of signs material To. these drugs. Delirium tremens at alcoholics is also regarded as functional K. Funktsionalnaya K. manifestation is observed, as a rule, at repeated influences of the substances possessing irreversible action. So, e.g. organophosphorous connections (see) (diizopropilftorfosfat, etc.) inhibit acetylcholinesterase it is almost irreversible (at many o'clock and days). At repeated influences of small doses of these substances amount of acetylcholinesterase, gradually decreasing, it can be insufficient for an inactivation of synoptic acetylcholine owing to what signs develop To. Effect of cytotoxic substances also has lines functional To.
Bibliography: Goldstein A., Aronow L. and. To and 1 m a n S. M of Principles of drug action, p. 326, N. Y., 1974.
I. V. Komissarov.