MUSCLE RELAXANTS (Greek mys, my[os] muscle + lat. relaxare to weaken, soften; synonym muscular relaxants) — the pharmaceuticals reducing a tone of skeletal muscles and causing in this regard decrease in a physical activity up to a full obezdvizhennost.
Distinguish M. of the central and peripheral types of action.
K M. peripheral action carry kurarepodobny substances (see), to-rye cause a relaxation of skeletal muscles due to blockade of neuromuscular transmission (see. Synapse ). According to the nature of influence on neuromuscular transmission distinguish from drugs of this group the substance which is depolarizing (Dithylinum, etc.), not depolarizing (tubocurarine Diplacinum, qualidil, etc.) and mixed (dioxonium, etc.) types of action. Besides, of peripheral action it is possible to refer to M. pharmacological the active connections exerting the direct oppressing impact on a tone and contractility of skeletal muscles by decrease in allocation of ions of Ca 2+ from a sarcoplasmic reticulum of muscular tissue. Unlike kurarepodobny means such connections oppress direct excitability of skeletal muscles and do not influence neuromuscular transmission. Thus, these substances can be considered as peripheral M. of direct myotropic action.
Treats drugs of this group dantrolen (Dantrolene; 1 - [(5-arilfurfuriliden) amine] - hydantoin), to-ry it is applied in medical practice of hl. obr. in the form of sodium salt (Dantrolene sodium; synonym of Dantrium). Along with a relaxation of muscles dantrolen exerts a nek-swarm the oppressing impact on c. N of page. However unlike M. of the central type of action it does not influence the central mechanisms of regulation muscle tone (see). Sensitivity of various groups of skeletal muscles to a dantrolen is not identical (muscles of extremities are more sensitive to its action, what respiratory muscles). Drug is well soaked up at various ways of introduction, and including from went. - kish. a path, it is slowly metabolized in a liver and allocated with kidneys preferential in the form of inactive metabolites and partially in not changed look. Its elimination half-life from an organism — apprx. the 9th hour.
K M. central action carry so-called mianezinopodobny (mefenezinopodobny) substances, to-rye on the properties and the mechanism of the muscular weakening action are close to Myanesinum (Mephenesinum) — the first drug of this group implemented in medical practice. On chemical structure of M. of the central action it is possible to divide into the following groups: 1) derivatives of a pro-pan-diol — Myanesinum, Meprotanum (see), Isoprotanum (see), etc.; 2) derivatives of an oksazolidin — metaalone, hlorzoaksazon; 3) benzodiazepines — diazepam (see), chlordiazepoxide (see) etc.; 4) drugs of a different chemical structure — orfenadrin, etc. Properties M. of the central action also Mydocalmum has.
In M.'s experiment of the central action reduce a spontaneous physical activity of animals and reduce a muscle tone. In very high doses they cause sluggish paralysis of skeletal muscles and an apnoea, caused by a relaxation of respiratory muscles. In subparalytic doses of M. of the central action eliminate at animals of the phenomenon of a cerebrate rigidity and hyperreflexia, weaken the spasms caused by strychnine and electric current. Besides, M.'s most of the central action has sedative, and nek-ry drugs (e.g., benzodiazepines, Meprotanum) tranquilizing properties and ability to exponentiate action of somnolent and analgetic means.
Unlike M. of peripheral action the central M. even in sublethal doses practically do not influence neuromuscular transmission or direct excitability of skeletal muscles. The mechanism of myshechnorasslablyayushchy effect of drugs of this group is caused by their oppressing influence on synoptic transfer of excitement to c. N of page. The general property of the central M. is ability to suppress activity of internuncial neurons of polisinaptichesky reflex ways of a spinal cord and nek-ry overlying departments of c. N of page. In this regard M. of the central action actively oppress polisinaptichesky reflexes and significantly do not influence monosinaptichesky reflexes. A certain value in the mechanism of action of the central M. has also oppression of the brake and facilitating influences descending from a number of nadsegmentarny structures (a reticular formation, subcrustal kernels) on motoriums of a spinal cord.
M use in various fields of medical practice for decrease in a tone of skeletal muscles. At the same time the choice of drugs for this or that purpose is carried out taking into account the width of their mioparalitichesky action. So, the vast majority of the kurarepodobny substances which are depolarizing, not depolarizing and the mixed types of action having the small width of mioparalitichesky action use for total muscle relaxation of hl. obr. in anesthesiology, and also at treatment of tetanus and for prevention of traumatic complications during the performing electroconvulsive therapy.
The central M., dantrolen and kurarepodobny means from among basic nitriles — Mellictinum (see), etc. — have the big width of mioparalitichesky action that allows to use them for decrease in a muscle tone without oppression or switching off of spontaneous breath. Such drugs use at the diseases which are followed patol, increase in a tone of skeletal muscles. In nevrol, practice, e.g., they are applied at spastic conditions of various origin (cerebral and spinal paralyzes, Littl's disease, a spastic wryneck, etc.). M of the central action apply also at muscular contractures traumatic or inflammatory (e.g., at rheumatic diseases) origins. Use of drugs of this group at the specified pathology promotes not only to reduction of pain in muscles of the struck area (owing to decrease in a tone of muscles), but also allows to carry out more effectively rehabilitation of patients since elimination of contractures facilitates carrying out to lay down. physical cultures. In anesteziol, the practician M. of the central action and dantrolen use relatively less than kurarepodobny substances, and apply according to other indications.
Collateral influence of M. of the central action and a dantrolen is shown by hl. obr. weakness, drowsiness, dizziness, dispeptic frustration. Emergence of allergic reactions is possible. Persons should not appoint the specified drugs in operating time, the profession to-rykh demands exact and bystry mental and motor reactions (drivers of transport, etc.).
Use of miorelakeant in anesthesiology
In anesthesiology for achievement of a deep muscular relaxation during the performing surgeries, nek-ry diagnostic procedures and artificial ventilation of the lungs is used by drugs from group of kurarepodobny substances. Depending on the estimated duration of an operative measure or the diagnostic procedure the choice of separate kurarepodobny drugs is made taking into account duration of their action. So, for short-term (within several minutes) (at an intubation of a trachea, reposition of dislocations, reposition of bone fragments, short-term operations and diagnostic procedures) it is reasonable to muscle relaxation to use kurarepodobny drugs of short action, napr, Dithylinum (see), tubocurarine (see), anatruksoniya (see), pavulon, etc.; drugs with a big duration of action are used by hl. obr. for maintenance of long muscle relaxation during operations under anesthetic with the managed breath, at artificial ventilation of the lungs, difficult and long diagnostic procedures. Dithylinum for achievement of long muscle relaxation can be used only on condition of its introduction in the fractional way or by method of drop infusion. By means of kurarepodobny drugs it is possible to cause a total or partial block of neuromuscular transmission. Resort to total blockade during the long operations demanding deep muscle relaxation and which are carried out, as a rule, in the conditions of endotracheal general anesthesia (see. Inhalation anesthesia ).
In cases when total muscle relaxation is not required. but during operation relaxation of muscles of a certain part of a body (a stomach, extremities) can be necessary, carry out a partial block of skeletal muscles introduction of small doses of kurarepodobny drugs. Drugs of not depolarizing type of action are most convenient for this purpose.
Due to the preservation of spontaneous breath operative measures in this case can be executed under a mask anesthesia on condition of careful overseeing by a condition of gas exchange and readiness to compensate by it disturbances by auxiliary or artificial ventilation of the lungs (see. Artificial respiration ). A technique of carrying out total muscle relaxation at the anesthesia which is carried out by means of special masks (see. Anesthetic inhaler ) without intubation of a trachea, was not widely adopted.
At the combined use of kurarepodobny drugs it is necessary to remember that introduction of a usual dose of not depolarizing substances (e.g., tubocurarine) after numerous injections of Dithylinum calls deeper and long neuromuscular block, than in usual conditions. Repeated introduction of Dithylinum after use of not depolarizing drugs in usual doses after short-term antagonism leads to deepening of the neuromuscular block of competitive type and tightening of the period of recovery of a muscle tone and breath. For assessment of nature of the neuromuscular blockade caused by kurarepodobny drugs the method can be used electromyography (see). Elektromiograficheski the nedepolyarizatsionny neuromuscular block is characterized by the gradual decrease in amplitude of action potential of a muscle without the previous simplification of neuromuscular transmission and muscular fastsikulyation expressed by a pessimum of frequency of irritation and a phenomenon of post-tetanic simplification. The passing simplification of neuromuscular transmission which is followed by muscular fastsikulyation and bystry subsequent development of the neuromuscular block is characteristic of the depolyarizatsionny (two-phase) neuromuscular block. In the first phase amplitude of single action potential of a muscle is reduced, the tetanus is steady, the phenomenon of post-tetanic simplification is absent. In the second phase the frequencies of irritation which are more or less expressed a pessimum and phenomenon of post-tetanic simplification of neuromuscular transmission come to light. Elektromiografichesky signs of the second phase are noted already at the first introduction of Dithylinum and dioxonium, and with increase in number of injections expressiveness and stability of these signs increase.
Use of kurarepodobny drugs at a myasthenia represents a special problem. Patients myasthenia (see) are extremely sensitive to drugs of the depolarizing type. Introduction of a standard dose of Dithylinum by it leads to development of the two-phase neuromuscular block with pronounced signs of the second phase in this connection repeated injections of drug can lead to excessively long and deep muscle relaxation, disturbance of recovery of breath and a muscle tone. At operational treatment of a myasthenia the technique of an autokurarization which is in a dose decline or cancellation of antikholinesterazny means before operation, use of the minimum dose of Dithylinum at an intubation and carrying out a hyperventilation during operation that allows to avoid repeated administrations of this drug gained distribution or to be limited to its minimum doses.
There are no absolute contraindications to use of kurarepodobny means, however at nek-ry diseases separate drugs of this group can be contraindicated. Therefore the rational and reasonable choice of kurarepodobny drugs taking into account character of the basic and associated diseases is of great importance. So, at patients with a renal failure, disturbances of water and electrolytic balance, acidosis, a hypoproteinemia hypersensitivity to M. from group of kurarepodobny substances of not depolarizing type of action (tubocurarine, etc.), and also to kurarepodobny drugs of the mixed type of action (to dioxonium, etc.) in connection with disturbance of distribution and elimination of these drugs is noted. Decrease of the activity of pseudo-cholinesterase — the enzyme which is carrying out hydrolysis of this drug (is the frequent reason of unusually long action of Dithylinum at genetic defects of enzyme, diseases of a liver, malignant new growths, hron, suppurative processes, bleedings, exhaustion). It is undesirable to apply Dithylinum during eye operations and at patients with the increased intracranial pressure in connection with its ability to increase intraocular and intracranial pressure. Use of Dithylinum is dangerous also at persons with extensive burns, a paraplegia, a long immobilization.
Complications at use of kurarepodobny means are substantially caused by the irrational choice of drugs for this patient, and also use of drugs without the nature of their interaction among themselves and with drugs from other groups of pharmaceuticals. The most frequent complication at use of kurarepodobny means in anesthesiology is prolonged by an apnoea — unusually long respiratory depression and a muscle tone after use of an average dose of drug. After administration of drugs of competitive type, and also dioxonium prolonged by an apnoea can develop at patients with a renal failure, acidosis, disturbances of water and electrolytic balance, a hypovolemia and as a result of exponential influence of nek-ry drugs (the general and local anesthetics, ganglioblokator, quinidine, dipheninum, beta adrenoblockers). The numerous injections of Dithylinum preceding administration of tubocurarine can also promote development of the prolonged apnoea. Miopa-ralitichesky action of Dithylinum is exponentiated clearly by antikholinesterazny means, Propanididum, aminazine, cytostatics (Cyclophosphanum, sarcolysine), Trasylolum. Besides, the reason of the slowed-down recovery of breath and a muscle tone after use of Dithylinum can be hypercapnia (see) and respiratory acidosis (see). For a dekurarization widely use the antikholinesterazny means (prozerin, Galantaminum, etc.) blocking cholinesterase and promoting that to accumulation of acetylcholine in neuromuscular synapses that leads to simplification of neuromuscular transmission, normalization of breath and a muscle tone. Perhaps also use of the means increasing synthesis and allocation of acetylcholine in neuromuscular synapses (dzhermin, pimadin and less effective a hydrocortisone, pantothenate of calcium).
The terrible, though rather rare complication connected using kurarepodobny substances is the rekurarization. Understand deepening of residual muscle relaxation up to an apnoea as a rekurarization or sharp respiratory depression, a cut develops, as a rule, in the first two hours after operation under the influence of a number of the factors breaking distribution, metabolism and elimination of drugs. A respiratory and metabolic acidosis, disturbances of water and electrolytic balance, a hypovolemia, arterial hypotonia, influence of nek-ry drugs (antibiotics from group of aminoglycosides, quinidine, Trasylolum, Cyclophosphanum), an inadequate dekurarization antikholinesterazny means at the end of operation belong to such factors.
After introduction of Dithylinum and, to a lesser extent, dioxonium there is a release of noticeable amounts of potassium from skeletal muscles in extracellular liquid therefore passing bradycardia quite often develops, is more rare — the atrioventricular block, is very rare — an asystolia (the last two complications are described only after use of Dithylinum).
Tubocurarine and qualidil have ability to release a histamine in this connection the passing tachycardia which is not demanding usually special treatment is noted. Treats the rare complications connected using tubocurarine and other kurarepodobny substances of not depolarizing action so-called prozerinoustoychivy curarizations. Usually the reason of inefficiency of the antikholinesterazny means applied for the purpose of a dekurarization is their introduction against the background of very deep blockade of neuromuscular transmission or against the background of a metabolic acidosis. Cases of prozerinoustoychivy curarization after use of an average dose of tubocurarine against the background of numerous preliminary introduction of Dithylinum are described.
Treatment of complications: ensuring adequate artificial ventilation of the lungs up to recovery of a normal muscle tone and elimination of the reason of a complication.
In M.'s anesthesiology use also according to other indications. So, M. of the central action possessing the expressed tranquilizing action, napr, diazepam, Meprotanum, it is possible to use as means for premedication before anesthesia (see). Mydocalmum is applied during the carrying out electroanesthesias (see). Diazepam in a combination with a narcotic analgetic fentanyl is applied for a so-called ataralgeziya (the balanced anesthesia) during the performing nek-ry surgeries. Besides, M. of the central action sometimes use for suppression of a muscular shiver and decrease in heat production at hyper thermal syndrome (see). Ability to stop manifestations of this syndrome arising sometimes after use of inhalation anesthetics (e.g., Ftorotanum) and Dithylinum, has also dantrolen.
Bibliography: Harkevich D. A. Pharmacology of kurarepodobny means, M., 1969; The pharmacological basis of therapeutics, ed. by L. S. Goodman a. A. Gilman, p. 239, N. Y. a. o., 1975; Physiological pharmacology, ed. by W. S. Root a. F. G. Hoffmann, v. 2, p. 2, N. Y. — L., 1965; PinderR.M. o. Dantrolene sodium, review of its pharmacological properties and therapeutic efficacy in spasticity, Drugs, v. 13, p. 3, 1977.
V. K. Muratov; V. Yu. Sloventantor, Ya. M. Hmelevsky (anest).