KURAREPODOBNY SUBSTANCES (synonym Muscle relaxants of peripheral action) — the medicinal substances blocking neuromuscular transmission and causing relaxation of skeletal muscles. Originally mioparalitichesky properties were found at curare (see). Therefore the substances causing similar effect are called kurarepodobny substances. On sources of receiving distinguish: To. century of a plant origin — tubocurarine (see), Mellictinum (see), semi-synthetic — Diplacinum (see) and synthetic — anatruksoniya (see), diadoniya (see), dioxonium (see), Dithylinum (see), qualidil (see), pavulon, tsiklobutoniya (see), etc.
To. oppress neuromuscular transmission at the level of a postsynaptic membrane century, blocking N-holinoretseptory of trailer plates (see. Synapse ). However the neuromuscular block called different To. century, can have unequal genesis. In this regard on the mechanism of action To. divide into three groups century: anti-depolarizing, or not depolarizing, To. century (tubocurarine, anatruksony, Diplacinum, Mellictinum, etc.); depolarizing To. century (Dithylinum); To. century of the mixed type of action (dioxonium).
Anti-depolarizing To. block N-holinoretseptory century, without causing depolarization of a subsynaptic membrane, and interfere with the depolarizing action of acetylcholine. Proceeding from the principles of interaction about acetyl sincaline, anti-depolarizing To. can be competitive and non-competitive N-holinoblokatorami century. So, true competitive antagonism between is possible To. century (e.g., tubocurarine) and acetylcholine on influence on N-holinoretseptory of skeletal muscles. To. century, acting by such principle, call competitive. Are available it is also non-competitive the operating drugs (e.g., presto - a cash). In this case To. century and acetylcholine, apparently, interact with different receptor substrates of a trailer plate.
Depolarizing To. century, interacting with N-holinoretseptorami of skeletal muscles, cause permanent depolarization of a postsynaptic membrane. In the beginning development of depolarization is shown by muscular fibrillations, neuromuscular transmission is quickly facilitated and after this the mioparalitichesky effect occurs.
To. century the mixed type of action differs, as a rule, in a combination of the depolarizing and anti-depolarizing properties. So, e.g., dioxonium causes depolyarizatsionno-non-competitive neuromuscular block.
To. relax muscles in a certain sequence century. The majority of drugs first of all blocks neuromuscular synapses of face muscles and a neck, then — extremities and a trunk. Are steadier against action To. century respiratory muscles. In the last turn the diaphragm will be paralyzed that is followed by an apnoea.
The important characteristic is the so-called width of mioparalitichesky action, i.e. range between doses in which To. century muscles, and the doses necessary for dead stop of breath will paralyze the most sensitive to them.
On duration of mioparalitichesky action To. it is conditionally possible to subdivide into three groups century: short action (5 — 10 min.) — e.g., Dithylinum, diadony; average duration of action (from 20 to 60 min.) — tubocurarine, diilatsin, pavulon; long actions and I (60 min. and more) — anatruksoniya, tsiklobutoniya.
Activity and duration of action anti-depolarizing To. can change under the influence of some anesthetics century. So, ether and to a lesser extent Ftorotanum strengthen and prolong mioparalitichesky effect of the anti-depolarizing substances, and nitrous oxide, cyclopropane and drugs for a neyroleptanalgeziya do not influence their activity. Insignificant strengthening of the blocking effect of the anti-depolarizing drugs is possible at their introduction against the background of hexenal or Thiopentalum-natrium.
The choice of antagonists To. is based on the mechanism of their action century. For the anti-depolarizing (especially competitive) drugs active antagonists are antikholinesterazny means (see), napr, prozerin, Galantaminum; blocking acetylcholinesterase, they considerably increase concentration of free acetylcholine. It leads to «replacement» To. century with N-holinoretseptorov of a trailer plate and to recovery of neuromuscular transmission.
There are no antagonists, acceptable for practice, of the depolarizing means. Antikholinesterazny means cannot be for this purpose used since they not only do not eliminate the blocking effect depolarizing To. century, but usually strengthen and prolong it. The most widely applied depolarizing means of Dithylinum it can be terminated by introduction of the fresh citrated blood containing pseudo-cholinesterase, edges participates in hydrolysis of Dithylinum.
The majority To. has sharp selectivity of action concerning neuromuscular synapses century. At the same time they can influence also other links of a reflex arc. A number of the anti-depolarizing substances, especially tubocurarine, has moderate ganglioblokiruyushchy activity, the cut is one of manifestations decrease in the ABP, and also the oppressing influence on N-holinoretseptory of a sinocarotid zone and a medulla of adrenal glands. Anatruksony, tsiklobutony, diadony and pavulon have atropinopodobny effect on heart that leads to tachycardia.
Tubocurarine and some other drugs can cause the release of a histamine which is followed by decrease in the ABP, increase in a tone of muscles of bronchial tubes, etc.
Depolarizing To. exert a certain impact on electrolytic balance century. As a result of depolarization of a postsynaptic membrane ions of K+ leave skeletal muscles and contents them in extracellular liquid and in a blood plasma increases. It can be the cause of cardiac arrhythmias and muscular pains.
Ganglioblokiruyushchy influence depolarizing To. do not possess century. They stimulate N-holinoretseptory in high doses gangliyev and a medulla of adrenal glands, raising thereof the ABP. Besides, depolarizing To. stimulate proprioceptors (the annulospiral terminations) of skeletal muscles century, strengthening thus receipt of an afferent impulsation in c. N of page that can cause oppression of monosinaptichesky reflexes of a spinal cord.
On a chemical structure To. divide into two groups century — quaternary ammonium compounds (tubocurarine, anatruksony, diadony, dioxonium, Diplacinum, Dithylinum, qualidil, pavulon, tsiklobutony) and basic nitriles (Mellictinum).
The majority of quaternary ammonium compounds has about two cationic centers (positively charged a nitrogen atom). Mioparalitichesky activity depends on concentration of a charge in the cationic centers, character of the radicals shielding them, distance between them, and also on a structure of the central part of a molecule. At the expense of the cationic centers polar interaction of substances with anion structures of N-holinoretseptorov of skeletal muscles is carried out. Besides, a part is played by non-polar linkages. For the majority To. century the distance between quarternary nitrogen atoms in 1,4 — 1,5 nanometers is optimum that approximately corresponds to chain length from 10 carbon atoms. At the same time there are drugs and with other distance between the cationic centers.
To. century from group of quaternary ammonium compounds of a direct impact on c. N of page practically do not render that is connected with their poor permeability through a blood-brain barrier.
To. century from group of quaternary ammonium compounds are badly soaked up from went. - kish. path. Therefore they are entered parenterally (usually intravenously). Basic nitriles are well absorbed in intestines and in this regard are effective at intake.
Separate To. are exposed in an organism to zymolysis century. So, e.g., Dithylinum is hydrolyzed by pseudo-cholinesterase what short duration of its action is connected with. Are allocated To. century and their metabolites of hl. obr. kidneys.
To. century widely apply in anesthesiology during the carrying out various surgical interventions. Causing relaxation of skeletal muscles, they considerably facilitate carrying out many operations on bodies of a chest and abdominal cavity, and also on top and bottom extremities. To. apply at an intubation of a trachea, a bronkhoskopiya, at reposition of dislocations, reposition of bone fragments etc. Besides, century To. use at treatment of tetanus and at electroconvulsive therapy century.
Depending on the estimated duration of an operative measure it is reasonable to use drugs taking into account duration of their action.
In need of repeated introduction anti-depolarizing To. century their dose should be reduced by 2 — 4 times since as a result of cumulation the blocking effect and its duration of the subsequent injections of drugs increase.
Basic nitriles, effective at introduction inside (e.g., Mellictinum), sometimes appoint at diseases and patol, the states which are followed by the raised tone of skeletal muscles.
Side effect at different To. it is expressed century unequally. So, e.g., tubocurarine causes hl. obr. decrease in the ABP and in some cases a bronchospasm, anatruksoniya and tsiklobutoniya cause hypotension and tachycardia, qualidil — increase in salivation, perspiration and tachycardia. Dithylinum can cause increase in arterial and intraocular pressure, cardiac arrhythmias, muscular pains. With genetically caused insufficiency of pseudo-cholinesterase Dithylinum can cause in persons long an apnoea (to 6 — 8 hours and more instead of usual 5 — 7 min.).
To. it is necessary to apply with care at diseases of a liver and kidneys century, and also at senile age.
Considering that To. oppress century or completely switch off breath, they can be used in medical practice only in the presence of their antagonists and all necessary conditions for carrying out artificial ventilation of the lungs.
See also Muscle relaxants .
Bibliography: Mashkovsky M. D. Pharmaceuticals, p.1, page 276, M., 1977; Harkevich D. A. Pharmacology of kurarepodobny means, M., 1969, bibliogr.; Neuromuscular blocking and stimulating agents, ed. by J. Ctieymol, v. 1 — 2, Oxford — N. Y., 1972; Neuromuscular junction, ed. by E. Zaimis, V. a. o., 1976; The pharmacological basis of therapeutics, ed. by L. S. Goodman a. A. Gilman, N. Y., 1975.
D. A. Harkevich.