Muscle relaxants or muscle relaxants are drugs that cause the striated muscles to relax.

Classification of muscle relaxants.

The classification is generally accepted, in which muscle relaxants are divided into central and peripheral. The mechanism of action of these two groups differs in the level of impact on synapses. Central muscle relaxants affect the synapses of the spinal cord and medulla oblongata. And peripheral - directly to the synapses that transmit excitation to the muscle. In addition to the above groups, there is a classification that separates muscle relaxants depending on the nature of the impact.

Central muscle relaxants are not widely used in anesthetic practice. But drugs of peripheral action are actively used to relax skeletal muscles.

Allocate:

• depolarizing muscle relaxants;
• antidepolarizing muscle relaxants.

There is also a classification according to the duration of action:

• ultrashort - act 5-7 minutes;
• short - less than 20 minutes;
• medium - less than 40 minutes;
• long-acting - more than 40 minutes.

Ultrashort are depolarizing muscle relaxants: listenone, succinylcholine, dithylin. Short, medium and long-acting drugs are mainly non-depolarizing muscle relaxants. Short-acting: mivacurium. Medium action: atracurium, rocuronium, cisatracurium. Long-acting: tubocurorine, orphenadrine, pipecuronium, baclofen.

The mechanism of action of muscle relaxants.

Non-depolarizing muscle relaxants are also called non-depolarizing or competitive. This name fully characterizes their mechanism of action. Muscle relaxants of the non-depolarizing type compete with acetylcholine in the synaptic space. They are tropic to the same receptors. But acetylcholine is destroyed in a matter of milliseconds under the influence of cholinesterase. Therefore, it is unable to compete with muscle relaxants. As a result of this action, acetylcholine is not able to act on the postsynaptic membrane and cause the process of depolarization. The chain of conduction of the neuromuscular impulse is interrupted. The muscle is not excited. To stop the blockade and restore conductivity, anticholinesterase drugs, such as neostigmine or neostigmine, must be administered. These substances will destroy cholinesterase, acetylcholine will not break down and will be able to compete with muscle relaxants. Preference will be given to natural ligands.

The mechanism of action of depolarizing muscle relaxants is to create a persistent depolarizing effect that lasts about 6 hours. The depolarized postsynaptic membrane is unable to receive and conduct nerve impulses, the signal transmission chain to the muscle is interrupted. In this situation, the use of anticholinesterase drugs as an antidote will be erroneous, since the accumulated acetylcholine will cause additional depolarization and increase neuromuscular blockade. Depolarizing relaxants are mainly of ultrashort action.

Sometimes muscle relaxants combine the actions of depolarizing and competitive groups. The mechanism of this phenomenon is unknown. It is assumed that antidepolarizing muscle relaxants have an aftereffect, in which the muscle membrane acquires a stable depolarization and becomes insensitive for a while. As a rule, these are longer-acting drugs.

The use of muscle relaxants.

The first muscle relaxants were the alkaloids of certain plants, or curare. Then their synthetic counterparts appeared. It is not entirely correct to call all muscle relaxants curare-like substances, since the mechanism of action of some synthetic drugs differs from that of alkaloids.

The main area of ​​application of muscle relaxants has become anesthesiology. Currently, clinical practice cannot do without them. The invention of these substances made a huge leap in the field of anesthesiology. Muscle relaxants made it possible to reduce the depth of anesthesia, better control the functioning of body systems, and created conditions for the introduction of endotracheal anesthesia. For most operations, the main condition is good relaxation of the striated muscles.

The effect of muscle relaxants on the functioning of body systems depends on the selectivity of the effect on receptors. the more selective the drug, the less side effects from the organs it causes.

In anesthesiology, the following muscle relaxants are used: succinylcholine, dithylin, listenone, mivacurium, cisatracurium, rocuronium, atracurium, tubocurarine, mivacurium, pipecuronium and others.

In addition to anesthesiology, muscle relaxants have found application in traumatology and orthopedics for muscle relaxation during the reduction of dislocation, fracture, as well as in the treatment of diseases of the back, ligamentous apparatus.

Side effects of relaxants.

From the side of the cardiovascular system, muscle relaxants can cause an increase in heart rate and an increase in pressure. Succinylcholine has a dual effect. If the dose is small, it causes bradycardia and hypotension, if it is large - the opposite effects.

Depolarizing-type relaxers can lead to hyperkalemia if the patient's potassium level is initially elevated. This phenomenon occurs in patients with burns, major injuries, intestinal obstruction, tetanus.

In the postoperative period, undesirable effects are prolonged muscle weakness and pain. This is due to the ongoing depolarization. Long Recovery respiratory function may be due to both the action of muscle relaxants and hyperventilation, airway obstruction, or an overdose of decurarizing drugs (neostigmine).

Succinylcholine is able to increase pressure in the ventricles of the brain, inside the eye, in the cranium. Therefore, its use in the corresponding operations is limited.

Muscle relaxants of the depolarizing type, in combination with drugs for general anesthesia, can cause a malignant increase in body temperature. This is a life-threatening condition that is difficult to stop.

The main names of drugs and their doses.

Tubocurarine. The dose of tubocurarine used for anesthesia is 0.5-0.6 mg/kg. The drug should be administered slowly, over 3 minutes. During the operation, maintenance doses of 0.05 mg/kg are fractionally administered. This substance is a natural alkaloid of curare. It tends to reduce pressure, in large doses causes significant hypotension. The antidote of Tubocurarine is Prozerin.

Ditilin. This drug belongs to the depolarizing type of relaxants. It has a short but strong action. Creates well-controlled muscle relaxation. Main side effects: prolonged apnea, rise in blood pressure. There is no specific antidote. Drugs have a similar effect listenone, succinylcholine, muscle relaxan.

Diplatz in. Non-polarizing muscle relaxant. Lasts about 30 minutes. The dose sufficient for one operation is 450-700 mg. No significant side effects were observed with its use.

Pipecuronium. The dose for anesthesia is 0.02 mg/kg. It works for a long time, for 1.5 hours. Unlike other drugs, it is more selective and does not affect cardiovascular system.

Esmeron(rocuronium). Dose for intubation 0.45-0.6 mg/kg. Valid up to 70 minutes. Bolus doses during surgery 0.15 mg/kg.

pancuronium. Known as Pavulon. The dose sufficient for anesthesia is 0.08-0.1 mg/kg. A maintenance dose of 0.01-0.02 mg/kg is administered every 40 minutes. It has multiple side effects from the side of the cardiovascular system, as it is a non-selective drug. May cause arrhythmia, hypertension, tachycardia. Significantly affects intraocular pressure. It can be used for Caesarean section operations, as it does not cross the placenta well.

All these drugs are used exclusively by anesthesiologists-resuscitators in the presence of specialized respiratory equipment!

These drugs are practically an indispensable element of combined anesthesia. With their help, muscle relaxation is achieved not by a dangerous increase in the concentration of inhalation anesthetics, but by a break in the impulse from the nerve to the muscle. There are 4 types of muscle relaxants: depolarizing, competitive, mixed and central. The last two types are used very rarely in the clinic.

Depolarizing muscle relaxants (ditylin, listenone) cause persistent depolarization of the end plate of the neuromuscular synapse. As a result, after a short-term excitation (fibrillation), complete relaxation of the striated muscles occurs for 3-5 minutes. Under general anesthesia, the duration of action of depolarizing muscle relaxants is prolonged..

The mechanism of action of competitive muscle relaxants (tubarin, arduan, norcuron) is fundamentally different. It is based on their ability to prevent the interaction of acetylcholine with neuromuscular junction receptors. As a result, depolarization of the end plate of the synapse becomes impossible and persistent relaxation occurs. skeletal muscle duration 40-60 min.

By providing muscle relaxation, muscle relaxants allow for more superficial anesthesia, ventilation during surgery, creating a surgeon best conditions to perform the most complex surgical interventions.

Additional drugs. During anesthesia and surgery, it becomes necessary to use methods that allow you to actively influence some body functions. Thus, controlled hypotension, achieved with the introduction of short-acting ganglionic blockers (arfonad, hygronium), can reduce systemic blood pressure, reduce blood loss from the surgical wound, and improve microcirculation. The inhalation anesthetic halothane has the same effect.

With the help of infusion therapy, it is possible to change the volume of circulating plasma according to indications, to influence the level of osmotic and oncotic pressure, to change the concentration of electrolytes in the blood plasma, to influence blood rheology.

IVL does not just take on the functions of an external respiration apparatus. It improves gas exchange by increasing the functional capacity of the lungs, reduces energy consumption for the work of breathing. By changing the parameters of ventilation, it becomes possible to actively influence pCO 2 , CBS, vascular tone, and, consequently, the blood supply to tissues.

A combination of drugs for anesthesia: tranquilizers, neuroleptics, analgesics, anesthetics, muscle relaxants - and drugs and methods that actively affect the functions of organs and systems of the body, and defines the concept - modern combined anesthesia.

There are many combinations. At the same time, it is advisable to use "standard", tested by practice combinations of drugs for anesthesia, which define the concepts of "type of anesthesia" and "method of anesthesia".

There are combined inhalation general anesthesia, basic anesthesia, neuroleptanalgesia, ataralgesia, central analgesia. Combined anesthesia underlies methods such as controlled hypotension (hypertension) and artificial hypothermia (hyperthermia).

2240 0

Muscle relaxants - tubocurarine, diplacin, paramion, fluxedil, dithylin, prokuran and others - block the transmission of nerve impulses from the motor nerve to the striated muscle, causing relaxation of the skeletal muscles, including respiratory, up to apnea. Skeletal muscles, depending on the dose and the individual characteristics of the wounded person, relax in a certain sequence.

The muscles of the neck and limbs are paralyzed first, then the abdominals, ribs, and finally the diaphragm. However, in some people, even with a small dose of a relaxant, relaxation of the entire musculature can immediately occur. In addition, relaxation of the muscles of the limbs and the abdominal press while maintaining spontaneous breathing does not mean at all that the respiratory muscles remained outside the action of the relaxant. Their function inevitably suffers, which leads to disruption of gas exchange.

Therefore, muscle relaxants cannot be used without assisted or controlled breathing.

With sufficient provision of gas exchange, these drugs, paralyzing the skeletal muscles, do not have any negative effect on the functions of other organs and systems.

All muscle relaxants are available in the form of ampouled powders or aqueous solutions that retain activity for a long time; they are administered intravenously. Only dithylin in solution loses activity, therefore, for long-term storage, it is produced in the form of an amulated powder of 0.1; 0.25; 0.5; 1.0, which is dissolved before use in sterile distilled water or in saline.

To relax the muscles of the limbs and abdominals, 100 mg of diplacin, 6-8 mg of paramion, 2-3 mg of procuran, 20-25 mg of ditilin are sufficient. At the same time, ventilation of the lungs decreases by 40-50%, which requires auxiliary breathing. When carrying out the latter, the anesthetist tries to get in time with the natural breathing of the anesthetized, increasing the volume of inhalation by squeezing the bag of the anesthesia machine.

However, assisted breathing is less effective than artificial respiration. Therefore, if possible, artificial lung ventilation should be used, for which dinlacip is administered at a dose of 360-380 mg, and paramion at a dose of 14-16 mg.

The action of these drugs in the indicated doses lasts 40-50 minutes. If it is necessary to prolong muscle relaxation, repeated doses of diplacin and paramion are reduced by half and three times. Most corresponds to military field conditions ditilin. It is used for prolonged muscle relaxation in the form of fractional injections of 100-200 mg.

Complete relaxation of the muscles after the introduction of ditilin occurs in 30-40 seconds and lasts 7-15 minutes. The dose of prokuran is 6-8 mg, while apnea persists for 20-25 minutes.

The action of relaxants after anesthesia can be considered completely stopped after the patient can, at the request of the doctor, arbitrarily change the frequency and depth of breathing, shake hands, and raise his head. If, after anesthesia with muscle relaxants, the patient remains hypopneic, then against the background of ongoing artificial respiration, the so-called decurarization should be performed.

To do this, 0.5-1.0 mg of atropine is administered intravenously, and after the appearance of tachycardia, 1.5-2.5 mg of prozerin is also injected intravenously, but very slowly (3.0-5.0 ml of a 0.05% solution) . With a pronounced slowing of the pulse and abundant salivation, an intravenous injection of atropine at a half dose is quickly repeated.

The described decurarization is effective both after the use of antidepolarizing relaxants - diplacin and paramion, and in hypopnea after anesthesia with nrocurane and dithylin. Prozerin against the background of the action of atropine effectively eliminates hypopnea caused by the "double block" or "second phase" of the action of procurane and ditilin.

Muscle relaxants, causing muscle relaxation, facilitate the work of the surgeon, create conditions for a less traumatic surgical intervention. They weaken the reflex reactions going along the somatic pathways and cause weak inhibition in the ganglia of the autonomic nervous system, which increases the resistance of the operated person to shock. Anesthesia can be carried out at the superficial (most safe) level.

Muscle relaxants in the wounded at the stages of medical evacuation with mandatory assisted or artificial respiration can be used in the following cases:
1) to facilitate intubation after induction anesthesia with sodium thiopental, hexenal, halothane, ether, nitrous oxide;

2) in order to provide the most perfect superficial anesthesia with low consumption of the main narcotic substance and to increase the resistance of the operated person to shock;

3) to relax muscles during endotracheal anesthesia during operations: a) on the abdominal and thoracic cavities, b) on the limbs to facilitate the reposition of bone fragments and the reduction of dislocations;

4) to turn off natural breathing if it is necessary to use artificial lung ventilation as a method of treating respiratory failure and terminal conditions.

A.N. Berkutov

Steroid derivatives

Atracurium

table 2

Classification of muscle relaxants by mechanism

2. Basic information about the structure and function of the neuromuscular synapse

3. Mechanism of action of muscle relaxants

4. Influence of muscle relaxants on the main functional systems of the body and metabolism.

5. Indications for the use of muscle relaxants in anesthesiology and resuscitation.

6. Characteristics of the main drugs, methods of their application

7. Control of neuromuscular conduction

8. The essence of decurarization and the methodology for its implementation

9. Complications associated with the use of muscle relaxants, their prevention and treatment

10. Prospects for the use of muscle relaxants in military field conditions

Literature:

Lecturer at the Department of Anesthesiology and Intensive Care

Introduction

Back in the 16th century. it became known that the South American Indians use poisoned arrows for hunting and war, the poison of which - curare - causes death due to paralysis of the respiratory muscles.

After Harold Griffith published the results of using a purified extract of curare during anesthesia in 1942, muscle relaxants quickly won a worthy place in the arsenal of anesthesiologists and resuscitators.

The discovery of the active principle of curare tubocurarine had a huge impact on the development of anesthesiology and surgery and made it possible to study the mechanism of neuromuscular transmission.

1. general characteristics and classification of muscle relaxants by chemical structure and mechanism of action

Muscle relaxants are drugs that block neuromuscular transmission. They are used to carry out controlled mechanical ventilation of the lungs, create conditions for the work of the surgical team, especially during operations on the organs of the chest and abdomen, to reduce intracranial hypertension, reduce oxygen consumption, eliminate trembling, ensure immobility during certain diagnostic manipulations, relieve convulsive syndrome and in a number of cases. other cases.

All blockers of neuromuscular transmission are chemically similar to acetylcholine. So, for example, succinylcholine actually consists of 2 molecules of acetylcholine (slide). Non-depolarizing relaxants hide their acetylcholine-like structure in the form of 2 types of ring systems - isoquinoline and steroid (slide). The presence of one or two quaternary nitrogen atoms in all blockers of neuromuscular transmission makes these drugs poorly soluble in lipids, which prevents their entry into the CNS.

All neuromuscular transmission blockers are highly polar and inactive when taken orally. They are administered only intravenously.

Table 1 (slide).

Classification of muscle relaxants by chemical structure

According to the mechanism of action, muscle relaxants are divided into 2 classes: depolarizing and non-depolarizing. In addition, muscle relaxants are divided according to the duration of action (slide, table).

table 2

Classification of muscle relaxants by mechanism and duration of action

In order to understand the mechanism of action and the use of modern muscle relaxants, let us first recall how neuromuscular transmission is carried out.

2. Basic information about the structure and function neuromuscular synapse

The slide shows a schematic structure of the neuromuscular synapse. On approaching the muscle fiber, the axon loses its myelin sheath and branches into many terminal branches (terminals). The surface of each such branch, directly adjacent to the muscle, is called the presynaptic membrane and, together with the so-called end plate (the section of the muscle fiber at the point of contact with the nerve ending), forms a neuromuscular synapse.

The nerve terminal contains a large number of mitochondria and vesicles with the mediator acetylcholine. Between the pre- and postsynaptic membranes there is a space filled with gel and called the synaptic cleft.

The end plate membrane (postsynaptic membrane) forms multiple folds. On the postsynaptic membrane are n-cholinergic receptors. The postsynaptic membrane is polarized at rest. Potential difference between external and inner surface membrane (resting potential) is 90 mV.

The process of neuromuscular transmission is as follows. The excitation coming along the axon in the form of an action potential activates calcium channels, facilitating the entry of calcium into the nerve fiber. An increase in the calcium concentration inside the nerve terminal leads to the fusion of the vesicular membrane with the membrane of the nerve ending and the release of acetylcholine from the vesicles into the synaptic cleft. Further, acetylcholine binds to the cholinergic receptors of the postsynaptic membrane, which leads to the opening of ion channels and the transition along the concentration gradient of Na and Ca into the cell and the release of K from the cell. The rapid movement of Na into the cell causes depolarization of the membrane (due to a decrease in the negative charge of the internal surface of the membrane), and the potential of the end plate, with a certain number of receptors associated with acetylcholine, reaches such a value that it spreads to neighboring sections of the muscle fiber in the form of an action potential, leading to a contraction muscles.

Acetylcholine is rapidly hydrolyzed by the specific enzyme acetylcholinesterase into choline and acetic acid. Enzyme molecules are fixed in the end plate in close proximity to cholinergic receptors.

The end plate released from acetylcholine returns to its previous state. The channels close, electrolytes return to their previous levels due to active transport. The muscle relaxes. After a short refractory period, during which the resting potential is restored, the membrane again becomes ready to respond to the next portion of acetylcholine entering the synaptic cleft, and the muscle to respond to the incoming action potential by contraction.

Now we can talk about the mechanism of action of different groups of muscle relaxants.

3. Mechanism of action of muscle relaxants

A. Non-depolarizing relaxants.

At low doses, they act on nicotinic receptors as competitive antagonists of acetylcholine. At high doses, some of the drugs in this group penetrate directly into the pores of the ion channels, further weakening neuromuscular transmission. In addition, non-depolarizing muscle relaxants can block presynaptic channels, hindering the transport of acetylcholine from nerve endings to the synaptic cleft. An important consequence of the competitiveness of their action is the ability of cholinesterase inhibitors to reduce or even completely stop the blockade.

B. Depolarizing muscle relaxants.

They operate in 2 phases. The first - depolarizing, is associated with the action of succinylcholine, similar to acetylcholine, with the depolarization of the end plate. Moreover, succinylcholine can penetrate into ion channels, causing “flickering” changes in conductivity in them.

For supporting muscle contraction a continuous supply of end plate potentials is required with the formation of a series of action potentials on the myocyte. To form the next potential of the end plate, it must first repolarize and then depolarize again. Since succinylcholine is not hydrolyzed rapidly in the synapse, the receptors remain blocked, repeated impulses from the end plate do not arrive, muscle fiber repolarized, muscle relaxation develops. This also contributes to the penetration of the drug directly into the channels.

In addition, there is a hypothesis according to which a non-excitable zone appears on the myocyte membrane around the end plate, which prevents the spread of excitation even when impulses are received from cholinergic receptors (desensitization, 2nd phase of the block). This is observed with the introduction of a large dose of succinylcholine.

It should be emphasized that the mechanism of action of muscle relaxants has not yet been fully elucidated. Research started by G. Griffith in 1942 continues.

4. The effect of muscle relaxants on the main functional body systems and metabolism

As mentioned above, muscle relaxants, due to their chemical structure, are unable to penetrate the central nervous system, therefore, they do not affect its functions. It must be emphasized once again that the drugs of this group do not cause anesthesia, analgesia, or sleep.

Muscle relaxants act differently on the cardiovascular system. So vecuronium, pipecuronium, doxacurium and rocuronium practically do not cause changes in its functions.

To reduce the toxicity of a general anesthetic, drugs from other groups (neuroleptics, muscle relaxants) are additionally used. Muscle relaxants (curare-like substances) are drugs that in isolation turn off muscle tension due to the blockade of neuromuscular transmission. Muscle relaxants are used for the following purposes: 1) muscle relaxation during anesthesia, which helps to reduce the dose of anesthetic and the depth of anesthesia; 2) as a consequence of the blockade of neuromuscular impulse transmission - the use of mechanical ventilation; 3) to relieve convulsions, muscle hypertonicity, etc. The absence or sharp decrease in muscle tone is an essential component to provide pain relief during abdominal operations. It should be remembered that the introduction of muscle relaxants necessarily leads to the cessation of the work of the respiratory muscles and the cessation of spontaneous respiration, which requires mechanical ventilation. According to the mechanism of action, antidepolarizing (pavulon, tubocurarine, diplacin) and depolarizing (ditylin, listenone, muscle relaxin) muscle relaxants are isolated, according to the duration of action - short (ditylin, listenone) and long-term (pavulon, tubocurarine). After the end of the operation, prozerin, which is an anticholinesterase drug (decurarization), is administered to eliminate the effect of muscle relaxants.

35. Neuroleptanalgesia. Aspects of application.

Neuroleptanalgesia (NLA) is a method of intravenous analgesia based on the combined use of the powerful antipsychotic droperidol and the narcotic analgesic fentanyl. The advantage of the method is a peculiar effect on the central nervous system, characterized by a rapid onset of indifference to the environment, the absence of motor anxiety, and a decrease in the severity of vegetative and metabolic reactions to surgical aggression. NLA usually acts as a component of combined anesthesia or in combination with local anesthesia. Most often, NLA is performed against the background of mechanical ventilation with nitrous oxide. Indications for carrying out: prolonged heavy operations on all parts of the chest and abdominal cavities, especially on the heart, large vessels, as well as neurosurgical interventions of increased trauma; high-risk operations in patients in serious condition, elderly, with concomitant pathology; performing special operations that require constant contact between the surgeon and the patient (otology, neurosurgery, etc.). Absolute contraindications to NLA are found only in obstetrics and gynecology clinics with caesarean section until the fruit is removed. Relative contraindications to NLA are available for diseases of the extrapyramidal system, with bronchial asthma, drug addicts.

36. Regional methods of anesthesia (definition, classification, indications for use).

Regional methods of anesthesia are characterized by the achievement of the effect of anesthesia, switching off conduction in a particular nerve or nerve plexus, while maintaining the consciousness and breathing of the patient. Regional anesthesia class:

Conductor - block. transmission of an impulse to the ur of the nerve trunk or nerve plexus-epidural - a block of impulse transmission to the ur of the roots of the spinal nerves by introducing an anesthetic into EPIDURAL E space.-spinal - a block of impulse transmission to the ur roots of the spinal nerves by introducing an anesthetic into SUBDURAL space.-plexus - carried out by introducing an anesthetic solution into the area of ​​\u200b\u200bthe nerve plexus.

Common indications for regional anesthesia are: intraoperative analgesia; postoperative pain relief; treatment of chronic neuropathic pain, as well as pain associated with malignant tumors; conducting preventive analgesia (the likelihood of postoperative chronic pain syndrome will be much less if epidural anesthesia is started the day before knee arthroplasty, or the likelihood of phantom pain will be less when epidural anesthesia is started before, and not after amputation of the affected limb).