Review of the best modern muscle relaxants: action, classification and application. Clinical pharmacology of muscle relaxants Lecturer, Department of Anesthesiology and Intensive Care

To muscle relaxantsreferdrugs that are designed to relax muscles. Their important property is the ability to completely prevent the reflex activity of the muscles. Until now, muscle relaxants have been used exclusively in anesthesiology, as they contributed to the removal of muscle tone during operations..

Muscle relaxants are divided into depolarizing and non-depolarizing (their differences are quite complex and require certain knowledge in the field of medicine). According to the time of action, muscle relaxants are divided, respectively, into substances of ultra-short action (up to 7 minutes of action), short action (no more than 20 minutes), medium action (40 minutes) and, finally, long action (more than 40 minutes).

To depolarizing muscle relaxants include suxamethonium preparations - listenone, dithylin, succinylcholine. They are muscle relaxants of ultrashort action and differ from each other only in the salt that is part of the composition.

To non-depolarizing muscle relaxants short-acting include mivacurium. Non-depolarizing muscle relaxants of medium duration are atracurium, vecuronium, rocuronium, cisatracurium. Long-acting non-depolarizing muscle relaxants are pipecuronium, pancuronium, and tubocurarine.

Mechanism of action of depolarizing muscle relaxants

The structure of depolarizing muscle relaxants is similar to the acetylcholine molecule. When interacting with H-cholinergic receptors, suxamethonium preparations cause an action potential of a muscle cell. Thus, like acetylcholine, depolarizing muscle relaxants cause depolarization and stimulation of the muscle fiber. However, acetylcholinesterase does not act on suxamethonium preparations, as a result of which their concentration in the synaptic cleft increases. This leads to prolonged depolarization of the end plate and muscle relaxation.

The destruction of depolarizing muscle relaxants occurs by plasma cholinesterase.

Suxamethonium preparations

With the introduction of suxamethonium preparations, a complete neuromuscular blockade occurs within 30-40 seconds, which allows them to be used for tracheal intubation. The duration of the neuromuscular block is from 4 to 6 minutes. This time may increase with quantitative or qualitative insufficiency of plasma cholinesterase. The incidence of insufficiency is 1:3000.

Sometimes depolarizing relaxants can cause the second phase of the block - non-depolarizing block. Then the action of suxamethonium preparations acquires an unpredictable effect and duration.

Side effects of suxamethonium preparations

When using suxamethonium preparations, their high histamine effect should be borne in mind.

Side effects of depolarizing muscle relaxants on the cardiovascular system is expressed in rhythm disturbances, fluctuations in blood pressure and heart rate. Moreover, suxamethonium preparations often cause bradycardia.

Another side effect inherent in all depolarizing muscle relaxants is fasciculations, the presence of which is used to judge the onset of the drug's action. If the appearance of fasciculations is undesirable, then before the introduction of suxamethonium, precuraresis should be performed. This is the name of the method of introducing a non-depolarizing muscle relaxant (for example, 1 mg of arcuron) 5 minutes before the administration of suxamethonium to prevent the side effects of the latter.

A terrible side effect when using suxamethonium preparations is hyperkalemia. If the initial level of potassium is normal, then this side effect has no clinical significance. In conditions accompanied by an increase in the level of potassium in the blood (burns, extensive injuries, myopathy, tetanus, acute intestinal obstruction), the use of depolarizing muscle relaxants can be life-threatening.

A common side effect of suxamethonium preparations is muscle pain in the postoperative period.

The increase in pressure in the stomach cavity caused by muscle relaxants from the group of depolarizing drugs does not increase the risk of gastric reflux and pulmonary aspiration.

Succinylcholine increases intraocular pressure, which may limit its use in ophthalmic operations in the absence of precurarization.

Ultrashort muscle relaxants increase cerebral blood flow and intracranial pressure, which can also be prevented by precurarization.

Depolarizing muscle relaxants can cause malignant hyperthermia.

The introduction of suxamethonium in myotonia is dangerous - this can provoke generalized contractions (myoclonus).

A typical representative of the muscle relaxants most widely used in the CIS countries is dithylin.

Ditilin is available in ampoules of 2 ml as a 2% solution. With intravenous administration, the effect develops after 60 seconds and lasts 5-10 minutes, with intramuscular injection, muscle relaxation develops after 2-4 minutes and lasts 5-10 minutes.

Ditilin is successfully used for tracheal intubation, during broncho- and esophagoscopy, for short-term operations.

The mechanism of action of non-polarizing muscle relaxants

Molecules of non-depolarizing muscle relaxants compete with the acetylcholine molecule for the right to bind to the receptor. When the muscle relaxant binds to the receptor, the latter loses sensitivity to acetylcholine, the postsynaptic membrane is in a state of polarization and depolarization does not occur. Thus, non-depolarizing muscle relaxants with respect to choline receptors can be called competitive antagonists.

Non-depolarizing muscle relaxants are not destroyed by either acetylcholinesterase or blood cholinesterase.

Mivacurium- muscle relaxant, acting up to 20 minutes. Its use is limited due to the relatively common side effect of histamine release. In addition, the dependence of its metabolism on pseudocholinesterase does not allow complete decurarization with anticholinesterase drugs.

Having appeared on the market, mivacurium did not live up to the expectations of manufacturers, although it still has to be resorted to under certain conditions.

Atracurium (trakrium)- a muscle relaxant of medium duration of action. Available in ampoules of 2.5 and 5 ml. In 1 ml - 10 mg of the active substance.

Trakrium is used as a component of general anesthesia for tracheal intubation. Its action is especially useful in surgical interventions and to facilitate mechanical ventilation.

In adults, trakrium is used at the rate of 0.3-0.6 mg / kg. If additional administration of a muscle relaxant is necessary, the dose should be calculated in the amount of 0.1-0.2 mg / kg.

Children aged two years of atracurium are prescribed in the same dosages as adults. In children under two years of age, a muscle relaxant is used at the rate of 0.3-0.4 mg / kg against the background of halothane anesthesia.

Restoration of conduction after neuromuscular blockade caused by atracurium occurs after about 35 minutes.

Side effects of using Trakrium can be:

• transient decrease in blood pressure;
• skin hyperemia;
• bronchospasm;
• very rarely - anaphylactic reactions.

Verocuronium- non-depolarizing muscle relaxant of steroid structure. Verocuronium has little effect on histamine release and is cardiostable.

Cisatracurium (Nimbex), which is a stereoisomer of atracurium, is three times more powerful, although the time of onset of the effect and its duration are approximately the same as those of atracurium.

Cisatracurium is available in the form of ampoules of 2.5 and 5 ml of 2 and 5 mg.

As with all muscle relaxants, indications for the use of cisatracurium are tracheal intubation, maintaining muscle relaxation, and mechanical ventilation.

Nimbex is used for tracheal intubation at a dose of 0.15 mg/kg, the maintenance dose is 0.1 mg/kg.

Rocuronium (esmeron)- a non-depolarizing muscle relaxant of medium duration of action, a positive feature of which is the speed of the onset of the effect. In addition, minimal histamine release and negligible cardiovascular effects have made rocuronium a very popular drug in anesthesiology.

Esmeron is available in bottles of 5 ml, 10 ml and 25 ml. 1 ml contains 10 mg of rocuronium bromide.

The dose of rocuronium for tracheal intubation is 0.3-0.6 mg/kg, the maintenance dose is 0.15 mg/kg.

Pipecuronium (arduan, arcuron) refers to long-acting non-depolarizing muscle relaxants.

Arduan is available in ampoules of 2 ml (1 ml contains 4 mg pipecuronium bromide).

In adults, pipecuronium is used at the rate of 0.07-0.08 mg / kg, in children - 0.08-0.09 mg / kg. The effect of the drug lasts for 50-70 minutes.

Of the side effects of pipecuronium, bradycardia, hypotension, and rarely anaphylactic reactions should be noted.

Pankurina (pavulon)- available in ampoules for intravenous administration of 2 ml (1 ml contains 2 mg of pancuronium bromide).

In adults and children from four weeks of age, pancuronium is used at a dose of 0.08-0.1 mg / kg. The drug causes good muscle relaxation for tracheal intubation in 90-120 seconds.

Side effects from the cardiovascular system caused by pancuronium are a slight increase in heart rate and blood pressure.

tubocurarine is issued in the form of 1% solution in 1.5 ml ampoules.

Currently, tubocurarine is practically not used because of the arterial hypotension and tachycardia caused by it, which is a consequence of the increased release of histamine.

The onset of action of tubocurarine after 60-90 seconds. For intubation, a dosage of 0.5-0.6 mg/kg is used.

Ideal muscle relaxant

None of the currently used muscle relaxants meet the criteria for an ideal muscle relaxant. As you know, there are three types of relaxants: those with a rapid onset and short duration of action; intermediate-acting or long-acting drugs must be free of side effects and must be non-depolarizing.
The onset of the muscle relaxant depends on the strength and quality of the connections, i.e. the effect of less powerful muscle relaxants comes faster. Other requirements for an ideal muscle relaxant were also identified: an antidepolarizing mechanism of action, a rapid development of the effect, the absence of cumulation, side effects from the cardiovascular system, the release of histamine, rapid and complete reversibility of the effect when using anticholinesterase drugs, rapid elimination from the body, regardless of conditions of kidney and / or liver function or biotransformation into inactive metabolites. Muscle relaxants appear to be responsible for 50% of all adverse reactions during anesthesia. The most common side effects are tachycardia, cardiovascular collapse, urticaria, and bronchospasm. Such reactions most often develop with the use of succinylcholine (suxamethonium), less often with the use of benzylisoquinoline muscle relaxants, and very rarely with the use of steroidal muscle relaxants. According to the results of skin tests, the use of steroid muscle relaxants is practically not accompanied by the release of histamine. The lowest frequency of undesirable effects is observed when using pipecuronium and vecuronium. Rocuronium may cause pain at the injection site and mild increases in blood pressure and heart rate. Anaphylactoid reactions have been reported more frequently with rocuronium than with other muscle relaxants in France, Norway and New Zealand, but not in other countries. Allergic reactions develop in the presence of a substituted ammonium group in muscle relaxants, which is responsible for the development of allergic reactions. It has been proven that this effect is observed with the parallel use of drugs containing pholcodine. Studies have shown that folcodine sensitizes the immune system. The drug is freely available in many countries, which may explain the higher incidence of anaphylactoid reactions to muscle relaxants, especially rocuronium.

Comments

Of the depolarizing muscle relaxants that are used today in clinical practice, it is used succinylcholine (suxamethonium chloride, listenone).

Succinylcholine (SH) is a quaternary ammonium compound, which is two ACh molecules connected together. Two quaternary ammonium radicals N + (CH 3) 3 are able to bind to each of the α-subunits of the postsynaptic ACh receptor, changing its structural structure and opening the ion channel for a longer period than is observed when exposed to an ACh molecule. Thus, administration of CX initially results in depolarization and muscle contraction known as fasciculation. But because this effect lasts longer than usual, subsequent action potentials cannot pass through the ion channels and the muscle relaxes; repolarization in this case occurs spontaneously due to the blockade of subsequent action potentials.

The dose of SC required for tracheal intubation in an adult is approximately 1.5–2.0 mg/kg. This dose provides a rapid onset of action, as well as the development of a deep block within 1 minute. Anesthesiologists in Europe and the USA have abandoned the daily use of CX
due to its side effects. However, SC is the drug of choice.
in cases where rapid tracheal intubation is necessary, for example,
in a patient with a full stomach or in obstetric practice. It is also indicated in cases where intubation is expected to be difficult (due to anatomical reasons) as it provides optimal conditions for intubation.

The drug is very rapidly metabolized by plasma cholinesterase (pseudocholinesterase). Recovery after a neuromuscular block begins in 3 minutes and is completely completed within 12-15 minutes. The use of anticholinesterase drugs to prolong neuromuscular block is contraindicated when using CX. Cholinesterase inhibitors significantly prolong I phase of the depolarizing block. This is explained as follows:

Firstly, the inhibition of acetylcholinesterase leads to an increase in the concentration of ACh in the nerve ending, which additionally stimulates depolarization;

Secondly, anticholinesterase drugs inhibit the activity of pseudocholinesterase, thus slowing down the hydrolysis of CX. Some anticholinesterase compounds, such as organophosphates, can prolong the action of SC by 20-30 minutes.

Explanation: After initial excitation under the influence of CX, sodium channels close and cannot open again until end plate repolarization occurs. However, repolarization is not possible while the muscle relaxant is associated with cholinergic receptors. Since the sodium channels at the synapse remain closed, the action potential is depleted and the muscle cell membrane repolarizes, which leads to muscle relaxation. This blockade of neuromuscular conduction is called I phase depolarizing block. With an excessively high dose of a depolarizing muscle relaxant, the neuromuscular block begins to resemble a non-depolarizing one. This phenomenon has been named II phase of the depolarizing block.

The primary metabolite of CX (succinylmonocholine) has a much weaker neuromuscular block and is very slowly cleaved to succinyl acid and choline. About 10% of CX is excreted in the urine; its metabolism in the liver is very insignificant, but in plasma, the destruction of succinylcholine also occurs under the influence of other enzymes (nonspecific esterases). It should be noted that pseudocholinesterase (PChE) has a great ability to hydrolyze SC, and at a high rate; as a result, only a small fraction of the initial intravenous dose of SC reaches the neuromuscular ending and has a muscle relaxant effect. With structurally abnormal plasma cholinesterase, which may be due to hereditary factors, or with a decrease in its level in plasma, the duration of action of CX may increase significantly and unpredictably.

Hereditary factors of cholinesterase deficiency. The exact structure of plasma cholinesterase is now fully established. It is known that it is determined genetically (by autosomal genes). A number of hereditary anomalies in the amino acid sequence of cholinesterase have been identified. These anomalies are referred to as E u 1 . The most common deviation is caused by the atypical E a 1 gene, which is present in about 4% of Europeans. In the patient heterozygous for an atypical gene(E u 1 , E a 1), the action of a standard dose of SC can last 30 minutes, and in individuals homozygous for the atypical gene(E a 1, E a 1), the duration of action of CX sometimes exceeds 2 hours. In patients with atypical cholinesterase due to genetic abnormalities, the gradual clearance of the drug from plasma is carried out by non-specific esterases. In such cases, it was proposed to administer fresh frozen plasma as a source of cholinesterase, or to use anticholinesterase drugs, such as neostigmine, to reverse the neuromuscular block, but substances with anticholinesterase activity in this case lead to the development of a double block. To get out of this situation, you should:

Carefully monitor neuromuscular transmission up to the complete disappearance of signs of residual muscle relaxation.

Prolongation of neuromuscular blockade due to a cholinesterase defect is not a threatening condition, however, the risk of the patient's awareness of the development of such a clinical situation is quite high, especially after the end of the operation, when the anesthesiologist, who does not yet have any information about the prolongation of the neuromuscular blockade, tries to wake the patient. Therefore, it should be recalled again that anesthesia and mechanical ventilation should continue until complete restoration of neuromuscular conduction.

A patient who has a decrease in cholinesterase activity or an abnormal structure of this enzyme has been found to be informed about this. In addition, it is necessary to make an appropriate entry in the medical documentation (medical history, extract from it), as well as notify the next of kin of the patient.

In 1957 Kalow and Genest first proposed a method for determining structurally abnormal cholinesterase. If the plasma of a patient with a normal genotype is placed in a water bath and benzoylcholine is added to it, then due to a chemical reaction with plasma cholinesterase, light with a certain wavelength will be emitted. This radiation can be determined with a spectrophotometer. If dibucaine is also added to the plasma, then the reaction of benzoylcholine with cholinesterase will be inhibited and radiation will not be observed. The relative percentage of inhibition is called dibucaine number. Patients with normal cholinesterase have a high dibucaine number (77 to 83). In patients heterozygous for the atypical gene, this number is 45–68, while in homozygous patients it is less than 30.

Acquired factors of cholinesterase deficiency. Acquired factors do not increase the duration of neuromuscular block as much as genetic abnormalities. In this case, it is more likely not about hours, but about minutes. It should be noted that in these cases, plasma cholinesterase, as a rule, is structurally normal, and only a decrease in its activity or concentration is observed under the influence of certain causes. These include:

· liver disease(enzyme synthesis is reduced);

· oncological diseases with signs of metastasis, starvation, burns(enzyme synthesis is reduced);

· pregnancy: an increase in circulating blood volume (dilution effect) and a decrease in enzyme synthesis;

· anticholinesterase drugs(neostigmine, edrophonium, ecothiopat);

· drugs that are metabolized by plasma cholinesterase and thereby reduce its availability(etomidate, local analgesics of the ester group, methotrexate, MAO inhibitors, short-acting β-blocker esmolol);

· other medicines(metoclopramide, hexafluorenium);

· hypothyroidism;

· cardiopulmonary bypass, plasmapheresis;

· kidney disease with manifestation of their dysfunction.

There is an opinion that drugs that affect the duration of action of CX can have a similar effect on a non-depolarizing muscle relaxant. mivacuria, as well as hydrolyzable PCE.

Side effects of SH. Although CX is widely used in hospitals in the Republic of Belarus, it has a number of side effects that limit its use. The most important among them are:

1. Muscle pain. The reason for them, obviously, are fasciculations at the beginning of the action of the drug. Most often, pain is observed in young patients with good muscle mass. The pain occurs in such unusual places as the interscapular region, the diaphragm and is poorly eliminated by conventional analgesics. It can be reduced with a small dose of a non-depolarizing muscle relaxant given before CX ( precurarization), for example, 1–2 mg of pancuronium or 2.5–5 mg of atracurium. However, this method reduces the power of AC, which requires the introduction of a higher dose of the drug to obtain the same effect (this thesis is controversial and is not always confirmed during the monitoring of neuromuscular blockade).

2. Increased intraocular pressure. It was assumed that the increase in intraocular pressure was partly due to the contraction of the external eye muscles with the introduction of SC (fasciculations), but it turned out that precurarization does not prevent the development of this side effect. Moreover, it persists throughout the neuromuscular block. There is also speculation that CX may also increase intracranial pressure.

3. Increased intragastric pressure. With normal function of the esophageal sphincter, the increase in intragastric pressure due to the action of CX is usually insufficient for regurgitation of gastric contents. However, in patients with insufficiency of this sphincter, for example, with a hernia of the esophageal opening of the diaphragm, regurgitation is quite possible.

4. Hyperkalemia. In 1959, Paton found that during anesthesia with halothane, the administration of CX leads to an increase in serum potassium by 0.5 mmol / l. This effect is believed to be due to muscle fasciculation. A similar rise in potassium levels is observed in patients with renal insufficiency, and the initially high level of potassium after the administration of SC due to an additional increase in its concentration can lead to severe disturbances in cardiac rhythm and conduction, up to cardiac arrest. In some pathological conditions, accompanied by swelling of the muscle tissue or its damage, the release of potassium can be even more significant. This is most noticeable in patients with burns, when plasma potassium levels can reach 10 mmol/l and higher after the administration of SC. Precurarization is not useful in these patients and it is best to avoid SC in this case. Hyperkalemia when using CX can also occur in diseases of muscle cells or a violation of their innervation: muscular dystrophy, myotonic dystrophy and paraplegia. Cases of death of such patients due to hyperkalemia are described. The use of SC is not indicated in all cases of neuromuscular disorders.

5. The introduction of depolarizing relaxants can provoke the manifestation malignant hyperthermia syndrome .

6. Cardiovascular disorders. CX, like ACh, has muscarine- and nicotine-like effects. Direct vagostimulating (muscarine-like) effect is accompanied by sinus bradycardia, especially in patients with high vagal tone (children and physically strong people). This is most often observed in situations where premedication is carried out without atropine, as well as after the administration of repeated doses of the drug. The most pronounced manifestation of cardiovascular disorders caused by CX is nodal or ventricular extrasystole.

7. A significant disadvantage is the presence of high histamine-liberating effect.

9. Separate groups of muscle relaxants

11. Benzylisoquinoline compounds

12. Tubocurarine chloride (curare, d-tubocurarine). This muscle relaxant is made from the bark of a South American plant. Chondrodendron tomentosum and was already used by the Indians of South America as an arrow poison. He is the first muscle relaxant used in clinical practice . It is indicated for long-term operations (3-4 hours), when the question of early extubation of the patient is not raised, as well as in cases where a decrease in blood pressure is acceptable or desirable. The dose for intubation is 0.5–0.6 mg/kg. This is a drug with a long development of effect and long-term action.

13. The dose of tubocurarine required for intubation is 0.5-0.6 mg/kg, it is administered slowly over 3 minutes. Intraoperative relaxation is achieved with a loading dose of 0.15 mg/kg, which is replaced by a fractional injection of 0.05 mg/kg. Tubocurarine has a pronounced ability release histamine leading to the development of hypotension and the possible occurrence of compensatory tachycardia. These effects may be enhanced with the use of large doses of the drug, when its ganglioblocking properties begin to appear. The drug is excreted unchanged in the urine and partly in the bile. The presence of renal failure prolongs the action of the drug.

14. Bronchospasm is due to the release of histamine. Tubocurarine should not be used in bronchial asthma.

15. Atracuria besilat (trakrium). The drug was developed at Stenlake University of Strathclyde in the UK and introduced into clinical practice in 1981. Stenlake found that quaternary ammonium compounds spontaneously decompose at different temperatures and different pH values ​​(this phenomenon has been known for more than 100 years as Hoffmann degradation). Many of these compounds have the ability to cause neuromuscular blockage. In search of such compounds capable of decomposing at body temperature and pH, atracurium was synthesized.
In healthy patients, partial excretion of the drug by the kidneys (10%) is observed, and with the help of Hoffmann degradation it is eliminated,
probably only about 45% of the drug. For debilitated patients with deterioration in the excretory function of the liver and kidneys, Hoffmann degradation can be considered as a kind of "safety belt", since even under these conditions the drug will be excreted from the body. This reaction is a purely chemical process that is accelerated by a shift in pH to the alkaline side and with an increase in body temperature. In fact, pH has little effect on the rate of Hoffmann elimination, but lowering the patient's body temperature to 34 ºС significantly slows down the degradation of the drug and prolongs the neuromuscular block. Atracurium does not cause such a rapid onset of neuromuscular blockade as CX.

16. A dose in the range of 0.3–0.6 mg/kg (depending on the required duration of the block) provides adequate myoplegia for 15–35 minutes. Tracheal intubation can be performed 90 seconds after an IV injection of Trakrium at a dose of 0.5–0.6 mg/kg. Full block can be rolled over
additional injections of trakrium in doses of 0.1-0.2 mg / kg. At the same time, the introduction of additional doses is not accompanied by the phenomena of cumulation of the neuromuscular block. Spontaneous recovery of neuromuscular conduction occurs in about 25-35 minutes and is determined by the restoration of tetanic contraction to 95% of the original. The effect of atracurium can be quickly and reliably stopped by the administration of anticholinesterases together with atropine.

17. Atracurium is able to release histamine in large quantities, although 3 times less than CX. This is observed in cases where the dose of atracurium exceeds 0.5 mg / kg or the drug is administered too quickly. With an increase in plasma histamine levels of more than 1000 pg / ml, the patient may experience facial flushing and a transient decrease in blood pressure. The release of histamine can be reduced by slow (over 30-60 s) administration of atracurium, either by reducing the dose of the drug, or by fractional administration of the calculated dose. Prevention of cardiovascular disorders due to histamine release (but not histamine release) can be achieved with the help of H 1 and H 2 histamine receptor blockers, for example, cimetidine 4 mg / kg and diphenhydramine 1 mg / kg, administered 30 minutes before the introduction of atracurium can prevent the development of arterial hypotension, despite a 10–20-fold increase in plasma histamine levels. Atracurium does not have a vagolytic effect and does not cause blockade of autonomic ganglia.

18. Cisatracurium (Nimbex). This neuromuscular blocker was introduced into clinical practice in 1996. It is the R-cis-R´-cis isomer of atracurium (one of 10 isomers of the parent compound). This structural conformation leads to an increase in the potency of the drug and a significant reduction in the number of side effects due to a decrease in the release of histamine compared to atracurium. Cisatracurium is 3-4 times more potent than atracurium and has a longer duration of action.

19. The dose for intubation is 0.1-0.15 mg/kg, it is administered during
2 minutes, which causes a neuromuscular blockade of an average duration of action (25-40 minutes). Infusion at a dose of 1–2 μg/(kg×min) allows maintaining intraoperative muscle relaxation. Thus, cisatracurium is equally effective as vecuronium.

20. The main advantage of this drug is the absence of histamine release. It has been established that even 8-fold ED 95 cisatracurium (including with rapid intravenous administration - within 5 s) does not cause an increase in plasma histamine content and changes in the cardiovascular system, therefore, the drug provides cardiovascular stability and can be used in individuals with a burdened allergic history. Like atracurium, it undergoes the Hoffmann
degradation. The metabolite of cisatracurium is laudanosine and monoquaternary alcohol. As a consequence of this degradation occurring in plasma and extracellular fluid, the restoration of neuromuscular conduction does not depend on the dose and duration of the drug. Cisatracurium is not hydrolyzed by nonspecific plasma esterases. Approximately 23% of the drug is eliminated in an organ-dependent way, and about 16% of this amount is excreted through the kidneys. However, in patients with chronic renal failure, there is no increase in the duration of action of cisatracurium, since, in general, the clearance of the drug in this category of patients decreases slightly (by 13%). In hepatic insufficiency, the volume of distribution of the drug increases, although its pharmacodynamics change minimally.

21. Mivacurium chloride. It is hydrolyzed by plasma cholinesterase by 70–88% at the same rate as CX hydrolysis. This metabolic pathway provides a short duration of drug action. The duration of relaxation is 1/2 - 1/3 of the duration of the neuromuscular block of non-depolarizing intermediate-acting muscle relaxants and is approximately 2-3 times longer than that of CX.

22. The dose required for intubation is 0.15–0.2 mg/kg; tracheal intubation can be performed after 2-2.5 minutes. With fractional administration, first 0.15 and then another 0.10 mg / kg, intubation is possible after 1.5 minutes. The drug is used in children older than 2 years at a dose of 0.2 mg / kg. Due to the possible significant release of histamine, the drug should be administered slowly, over 20-30 seconds.

23. The short duration of the drug action makes it possible to maintain relaxation by infusion (especially during surgical interventions lasting 30-60 minutes or more). Infusion at an initial dose of 4–10 μg/(kg×min) allows for intraoperative muscle relaxation. At the same time, long-term infusions of mivacurium give a minimal lengthening of the recovery time of neuromuscular conduction. The recovery time does not depend on the dosing or infusion time of the drug. Elimination of the residual block is carried out by the appointment of anticholinesterase drugs or PChE donors (plasma, whole blood).

24. Mivacurium may cause histamine release. With its rapid introduction at a dose of 0.2–0.25 mg / kg, a transient decrease in blood pressure and flushing of the face can be observed. To minimize histamine release, the rate of muscle relaxant administration can be slowed down to 30 seconds. Mivacurium does not block the autonomic ganglia and does not have a vagolytic effect.

25. As already mentioned, mivacurium is almost completely hydrolyzed by PChE. Through the kidneys, unchanged, only about
5% of the drug. Metabolites of mivacurium - mivacurium monoester and amino alcohol, are eliminated in urine and bile. Although there is no direct dependence of the rate of elimination of mivacurium on the function of the kidneys and liver, however, the pharmacodynamics of the drug in hepatic or renal insufficiency is significantly impaired, which can lead to a lengthening of the neuromuscular block. For example, in renal failure, the duration of action of mivacurium increases by about 10-15 minutes.

26. Currently mivacurium is muscular relaxant of choice for one-day hospital operations , in endoscopic surgery. It can also be recommended for operations with unpredictable duration. However, this drug is not registered in the Republic of Belarus.

27. Aminosteroid compounds

28. Pancuronium bromide (pavulon). This long-acting muscle relaxant was the first of the steroid compounds to be used in the clinic. It is a bis-quaternary amine. Synthesized in 1964 Hewett and Savage and immediately gained recognition as a very powerful muscle relaxant that does not have a hypotensive effect. Pancuronium has a moderate vagolytic effect, and therefore May cause tachycardia and high blood pressure. Ideal for long-term surgery. The absence of histamine release during its use allows the use of the drug in patients with a aggravated allergic history.

29. The moderate vagolytic effect of pancuronium and its stimulation of the sympathetic nervous system usually cause an increase in heart rate, blood pressure and cardiac output. The mechanisms causing these manifestations are facilitation of ganglionic transmission by pancuronium, an increase in the release of catecholamines and a decrease in the reuptake of catecholamines by the presynaptic membrane.

30. The time from the moment of administration of the drug to the moment of development of the maximum effect (time of onset of action) varies depending on the administered dose. Time of onset of action at a dose of 0.06 mg/kg
5 minutes, and the duration of action from the moment of administration to the moment of recovery of 25% of muscle contractions is approximately 35 minutes, until the moment of recovery of 90% of contractions - 73 minutes. Higher doses cause a decrease in the time of onset of action and increase the duration.

31. Recommended doses for intubation - 0.08–0.1 mg/kg. Good conditions for intubation are provided within 90–120 s after an intravenous dose of 0.1 mg/kg and within 120–150 s after administration
0.08 mg/kg pancuronium.

33. Doses to maintain intraoperative muscle relaxation - 0.01-0.02 mg / kg every 20-40 minutes.

34. Pancuronium is slowly excreted through the kidneys unchanged. 10-20% of the drug is deacetylated in the liver. In severe violations of kidney and liver function, the total clearance of the drug decreases and the duration of its action increases significantly. The pancuronium metabolite is twice as weak as the main compound in terms of the power of the neuromuscular block, but it is similar to pancuronium in terms of duration of action and kinetics. When using pancuronium, inhibition of plasma PChE is observed, which prolongs the time of action of any drug that undergoes hydrolysis with its participation.

35. Pipecuronium bromide (Arduan). It is an analogue of pancuronium, the molecule of which contains two piperazine groups. Synthesized in 1982 in Hungary. Approximately 20-30% more powerful than pancuronium. Like pancuronium, it has a long-term effect.

36. The time to the development of the maximum effect and the duration depends on the dose. Measured by a peripheral nerve stimulator, 95% blockade is achieved in 2-3 minutes after the administration of SC, while without SC - in 4-5 minutes. For a 95% neuromuscular blockade after the application of SC, it is sufficient to inject 0.02 mg/kg of the drug, this dose provides surgical muscle relaxation for an average of 20 minutes. Blockade of similar intensity occurs without succinylcholine with the introduction of 0.03-0.04 mg / kg of the drug with an average duration of effect of 25 minutes. The duration of the effect of 0.05-0.06 mg / kg of the drug is on average 50-60 minutes with individual fluctuations.

37. Pipecuronium is slightly more powerful than pancuronium. The dose for intubation is 0.04-0.08 mg / kg, the optimal conditions for intubation occur after 2-3 minutes. If repeated administration is necessary, the use of 1/4 of the initial dose is recommended. At this dosage, cumulation does not occur. With the introduction of repeated doses, 1/2 - 1/3 of the initial dose can be considered as a cumulative effect. In case of insufficiency of renal function, it is not recommended to administer the drug at a dose of more than 0.04 mg / kg.

38. The vagolytic activity of the drug is about 10 times less than that of pancuronium. In addition, pipecuronium does not have a ganglioblocking effect and does not release histamine. In this regard, it has practically no effect on the cardiovascular system, providing a clear cardiovascular stability compared to pancuronium. Metabolic transformations of pipecuronium are very insignificant. Only about 5% of the drug undergoes deacetylation in the liver. The main route of excretion is through the kidneys. In severe violations of the liver and kidneys, there is a slowdown in the excretion of pipecuronium and an increase in its half-life.

39. Rocuronium(registered in the Republic of Belarus in June 2008). It is a medium-acting steroidal relaxant (30–45 min) with onset of neuromuscular block earlier than vecuronium. The duration of action of rocuronium is limited by the absorption of the drug by the liver and elimination with bile, which is explained by its increased lipophilicity compared to vecuronium.

40. Tracheal intubation is possible after 60-90 seconds when administered at a dose
0.5–0.6 mg/kg, which allows us to consider it an alternative to CX if urgent tracheal intubation is required.

41. The dose of rocuronium for intubation is 0.45–0.6 mg/kg, intubation can be carried out within 1 minute. The duration of the neuromuscular block in this case is 30 minutes, with an increase in the dose, the duration of the block increases to 50–70 minutes. To maintain intraoperative muscle relaxation, the drug is administered as a bolus at a dose of 0.15 mg/kg. The infusion dose varies from 5 to 12 µg/(kg×min). Duration
rocuronium in elderly patients increases significantly.

42. When administered at a dose of up to 1.2 mg/kg, rocuronium has a minimal effect on the cardiovascular system in both healthy patients and patients with cardiovascular pathology. The indicated dose does not lead to an increase in plasma histamine levels. The indications that it causes an increase in heart rate may be due to either the painful injection of rocuronium or its weak vagolytic effect. In general, rocuronium has practically no negative effect on the cardiovascular system at doses up to 0.6 mg/kg, and at higher doses (0.9-1.2 mg/kg) leads to an increase in heart rate by 10-25% of baseline due to its vagolytic properties.

43. The main route of elimination of rocuronium is metabolic transformations in the liver. About 10% of the drug is excreted through the kidneys. It is actively taken up by the liver via an active transport transport system. The putative metabolite of rocuronium is 17-deacetylrocuronium. In patients with hepatic insufficiency (most often with cirrhosis of the liver), the volume of distribution of rocuronium increases and its clearance may decrease. The duration of action of rocuronium in hepatic pathology is prolonged, therefore dosing of rocuronium in such patients should be done carefully, using careful monitoring of neuromuscular block. In renal insufficiency, the plasma clearance of rocuronium is also reduced, and the volume of distribution is increased, however, the duration of the drug's action with a single or repeated administration in this case does not change significantly. In elderly patients, the duration of action of rocuronium is increased.

Muscle relaxants are used in anesthesia to block neuromuscular transmission and provide skeletal muscle relaxation. The introduction of these drugs allows the anesthesiologist to perform tracheal intubation, facilitates ventilation and provides optimal conditions for surgical intervention, such as laparotomy.

The main mechanism of action of muscle relaxants is to prevent the interaction of acetylcholine with postsynaptic (nicotinic) receptors on motor neurons and the muscle membrane.

Peripheral muscle relaxants used in anesthesiology are divided into depolarizing and non-depolarizing.

Depolarizing muscle relaxants

Suxamethonium is the only representative of the group of depolarizing MR used in modern clinical practice.

Structurally, it is two molecules of acetylcholine (ACh) linked together and acts as a nicotinic receptor agonist. Suxamethonium binds to the receptor, which mimics the effect of ACh and leads to membrane depolarization. The process of depolarization is accompanied by muscle contraction, which develops rapidly and is clinically manifested in the form of fasciculations (muscle twitches).

After membrane depolarization, in order for it to repeat itself, a reset of the membrane potential must occur. Until the onset of the next depolarization, the skeletal muscle remains in a state of flaccid relaxation.

When administered intravenously at a dose of 1.0–1.5 mg/kg, suxamethonium causes a deep neuromuscular block already after 60 seconds, which exceeds the onset of the effect of any other available MR. Typically, neuromuscular blockage resolves spontaneously in about 10 minutes.

The drug undergoes rapid hydrolysis with the participation of plasma pseudocholinesterase with the formation of succinylmonocholine and choline. To prevent spontaneous hydrolysis, the drug should be stored at 4 °C.

Suxamethonium can be administered intramuscularly at a dose of 3-5 mg/kg, while compared with intravenous administration, its effect develops much later. The intramuscular route of administration is usually used only in infants when the venous route is not available.

Among all muscle relaxants, suxamethonium has the fastest onset of effect and its greatest predictability. In addition, the effect of the drug is very short-lived: recovery begins approximately from the 4th minute and ends by the 10th.

These characteristics make suxamethonium the drug of choice when rapid tracheal intubation is required, such as in emergency situations, or where rapid sequential induction is required due to the risk of aspiration. The drug will also be indicated if necessary in the rapid restoration of neuromuscular function.

Suxamethonium may have the following side effects:

• Bradycardia- develops due to stimulation of muscarinic receptors in the sinoatrial node of the heart. Bradycardia is more common in children and often develops after repeated administration of the drug or its use in high doses.

• Increased intraocular pressure. When suxamethonium is used in patients with a penetrating eye injury, there is a theoretical risk of vitreous leakage.

• Muscle pain- are quite common, especially in young, physically developed people, with early activation after the intervention. None of the methods of prevention does not completely prevent muscle pain. There are various techniques aimed at reducing the frequency of this complication, for example, precurarization. Precurarization consists of administering a low dose of a non-depolarizing muscle relaxant at least three minutes prior to the administration of suxamethonium.

• Hyperkalemia. The introduction of suxamethonium is accompanied by an increase in the plasma concentration of potassium by about 0.5 mmol / l. If the patient has initial hyperkalemia, a further increase in potassium concentration may be accompanied by a risk of arrhythmias and circulatory arrest.

• Increased pressure in the stomach. With the introduction of suxamethonium, there is an increase in pressure in the lumen of the stomach. However, a simultaneous increase in the tone of the lower esophageal sphincter will resist the expulsion of gastric contents and regurgitation.

• Anaphylaxis. More than 50% of cases of anaphylactic reactions associated with the use of muscle relaxants result from the administration of suxamethonium.

• Second Phase Phenomenon block may develop due to the introduction of suxamethonium in a high dose or as a result of repeated injections of the drug, when the neuromuscular block begins to resemble a non-depolarizing one. It is characterized by prolonged blockade.

• Prolonged block due to reduced plasma cholinesterase activity. Prolonged block may be due to hereditary or acquired causes. Hereditary causes of prolonged blockade in response to suxamethonium are associated with the formation of atypical plasma cholinesterase.

Acquired causes include reduced production of the enzyme, which may result from liver disease, carcinomatosis, pregnancy, starvation, heart and kidney failure, and burn disease. The use of a number of drugs, such as ethereal local anesthetics, methotrexate, remifentanil and esmolol, leads to a decrease in plasma cholinesterase activity.

• Malignant hyperthermia. Suxamethonium is a trigger for this extremely dangerous condition, and therefore its use is absolutely contraindicated in patients at risk.

Non-depolarizing muscle relaxants

Non-depolarizing muscle relaxants act as competitive antagonists of ACh at the level of postsynaptic nicotinic receptors. They bind to the receptor and prevent membrane depolarization in response to ACh stimulation. The binding of antagonists and receptors is reversible. Neuromuscular blockade begins to develop when 70–80% of the receptors are blocked, while 90% of the receptors must be occupied to form a complete block.

It is believed that non-depolarizing MRs also inhibit the presynaptic receptors of the neuromuscular junction, preventing further ACh mobilization.

Non-depolarizing MRs are not subject to metabolism at the level of the neuromuscular junction, so the resolution of the block is associated with a dilutional decrease in their concentration, i.e., washout from the receptors. These drugs are highly ionized and water-soluble, and therefore their volume of distribution approaches the volume of plasma and extracellular fluid.

Muscle relaxants of non-depolarizing action differ from each other in the different duration of the neuromuscular block, which allows them to be divided into three groups:

• Long acting muscle relaxants(tubocurarine, pancuronium, alcuronium). Common to the drugs of this group is the relatively slow development of the maximum neuromuscular block (from 3 to 6 minutes) after the introduction of a muscle relaxant in a dose sufficient for intubation. Restoration of the neuromuscular response to 25% of the norm with their use is observed after 80-120 minutes.

As a rule, non-depolarizing muscle relaxants of this group require the subsequent administration of drugs that accelerate the reversal of the neuromuscular block. All drugs in this group undergo extremely low metabolic transformations or are not metabolized at all and are excreted mainly through the kidneys in unchanged form.

• Intermediate action muscle relaxants(vecuronium, rocuronium, atracurium, cisatracurium). The onset of a neuromuscular block after the introduction of drugs of this group in an intubation dose occurs in 2–2.5 minutes. The duration of the clinical effect is 30-60 minutes, and 95% recovery of the response to stimulation occurs after 45-90 minutes.

In vecuronium and rocuronium, the average duration of action is due to the presence of two alternative routes of elimination from the body (liver and kidneys); in atracurium and cisatracurium, this feature is due to the fact that at a temperature of 37 °C spontaneous destruction of the drug molecule occurs with a decrease in the relaxation effect.

• Short acting muscle relaxants(mivacurium and rapakuronium). The effect after the introduction of mivacurium occurs after about 2 minutes, and the onset of action of rapakuronium - after 1 minute. The duration of the clinical action of mivacurium is 12-20 minutes, and 95% recovery of the convulsive response is observed at 25-35 minutes.

Rocuronium has the fastest onset of effect among all clinically available non-depolarizing MR. The duration of action of rocuronium is limited by the absorption of the drug by the liver and elimination with bile.

Tracheal intubation is possible after 60–90 s when administered at a dose of 0.5–0.6 mg/kg, which allows us to consider it an alternative to CX if urgent tracheal intubation is required. The duration of the neuromuscular block in this case is 30 minutes, with an increase in the dose, the duration of the block increases to 50–70 minutes.

To maintain intraoperative muscle relaxation, the drug is administered as a bolus at a dose of 0.15 mg/kg. The infusion dose varies from 5 to 12 µg/(kg×min). The duration of action of rocuronium in elderly patients is significantly increased.

When administered at a dose of up to 1.2 mg/kg, rocuronium has a minimal effect on the cardiovascular system in both healthy patients and patients with cardiovascular pathology. The indicated dose does not lead to an increase in plasma histamine levels. The indications that it causes an increase in heart rate may be due to either the painful injection of rocuronium or its weak vagolytic effect.

In general, rocuronium has practically no negative effect on the cardiovascular system at doses up to 0.6 mg/kg, and at higher doses (0.9-1.2 mg/kg) leads to an increase in heart rate by 10-25% of baseline due to its vagolytic properties.

The main route of elimination of rocuronium is metabolic transformations in the liver. About 10% of the drug is excreted through the kidneys. In patients with hepatic insufficiency (most often with cirrhosis of the liver), the volume of distribution of rocuronium increases and its clearance may decrease. The duration of action of rocuronium in hepatic pathology is prolonged, therefore dosing of rocuronium in such patients should be done carefully, using careful monitoring of neuromuscular block.

In renal insufficiency, the plasma clearance of rocuronium is also reduced, and the volume of distribution is increased, however, the duration of the drug's action with a single or repeated administration in this case does not change significantly. In elderly patients, the duration of action of rocuronium is increased.

The drug is used to reverse the neuromuscular block caused by rocuronium. Sugammadex(BRIDION), which is a specific chemical antagonist of muscle relaxants of a non-depolarizing type of action of an aminosteroid structure (rocuronium, vecuronium. It selectively binds to muscle relaxants of the aminosteroid series, which leads to the restoration of neuromuscular transmission. To muscle relaxants of the benzylisoquinoline series (atracurium, cisatracurium) and depolarizing muscle relaxants it has virtually no effect.

The possibility of complete reversal of the block - even with deep muscle relaxation - within 90 s, the subsequent possibility of re-intubation of the trachea within 60 s and the absence of adverse reactions is noted. The recommended doses for the immediate elimination of the block are 16 mg/kg, for the reversal of a deep neuromuscular block, 4 mg/kg, and for a shallow block, 2 mg/kg.

Muscle relaxants - drugs that are used in anesthesiology to relax skeletal muscles by interrupting the transmission of excitation from the nerve to the muscle. This transmission is carried out under the influence of acetylcholine, which is released when the nerve is excited. There are complex bioelectrical processes, which are called polarization, depolarization, repolarization. Since according to the mechanism of action, muscle relaxants affect these processes, they are conditionally divided into non-depolarizing and depolarizing.

Non-depolarizing (antidepolarizing) muscle relaxants - drugs that paralyze neuromuscular transmission, as they reduce the sensitivity of cholinergic receptors to acetylcholine and prevent depolarization of the end plate. All non-depolarizing relaxants should be given after tracheal intubation. and.

Tubocurarine chloride (tubarine) - Quaternary ammonium compound. It is used intravenously, the initial dose is 0.3-0.5 mg / kg. The action occurs in 3-5 minutes without muscle fibrillation. Muscle relaxation begins with the face - eyes, eyelids, masticatory muscles, then pharynx, larynx, chest, abdomen and limbs; the diaphragm is the last to turn off. Recovery is in reverse order. Tubocurarine has a ganglioblocking and histamine-like effect, therefore, when it is used, a decrease in blood pressure and allergic reactions are possible. It is excreted in the urine and is very slowly inactivated. The duration of the first dose is 20-40 minutes, a second dose (1/2 of the original) gives a longer effect.

The drug is used during the maintenance of anesthesia, after tracheal intubation. It is used with caution in the elderly, with damage to the kidneys, liver. Tubocurarine is contraindicated in myasthenia gravis.

Pancuronium bromide (pavulon) - a synthetic steroid muscle relaxant, but hormonally inactive. Causes a non-depolarizing block. The initial dose is 0.08-0.09 mg / kg of body weight, the duration of action is 60-80 minutes; repeated dose - 0.02-0.03 mg / kg. The drug does not cause changes in hemodynamics and histamine effect.

close to him arduan (pipecurium bromide) - steroid, synthetic muscle relaxant without side effects on hemodynamics. It is widely used both during operations and in the postoperative period with artificial lung ventilation in children, adults and the elderly. The average dose is 0.07-0.08 mg / kg, the duration of action is 60-90 minutes; the repeated dose makes 1/2-1/3 initial.

Arduan is used for tracheal intubation at a dose of 0.07 mg / kg, with a contraindication to the introduction of ditilin. The drug is contraindicated in myasthenia gravis and early pregnancy. Pavulon and arduan are indicated in patients with increased operational risk.

Anatruxonius - antidepolarizing relaxant. The initial dose - 0.07 mg / kg, causes relaxation of the abdominal muscles, breathing is maintained, but becomes inadequate, which requires mechanical ventilation. At a dose of 0.15-0.2 mg/kg of weight, total muscle relaxation develops for 60-120 minutes. Usually repeated doses should be reduced by 3 times. The drug has not found wide application due to the prolonged action, tachycardia during surgery and ganglioblocking effect.

Diplacin - a synthetic drug of domestic production, administered at a dose of 3-4 mg/kg after tracheal intubation. The duration of action is 30-40 minutes, repeated doses are 1/2-1/4 of the initial one and cause prolonged apnea, which significantly limited its use.

Antidotes of all non-depolarizing relaxants are prozerin, galantamine, which are used for decurarization.

Muscle relaxants are antispasmodic drugs, the action of which is intended to relieve spasms in muscle tissue and eliminate increased muscle tone. This eliminates symptoms such as pain and numbness. Some drugs tend to completely inhibit muscle activity.

Indications and contraindications

Indications for the use of these drugs are the following pathologies, accompanied by spasm of muscle tissue:

• Osteochondrosis.
• Osteoarthritis.
• Lumbago.
• Spondylosis.
• Neuralgia.
• Radiculitis.
• Joint contracture.
• Vertebral protrusion.
• Intervertebral hernias.
• Spinal stenosis.
• Injuries of the neck, spine, limbs.

Also, antispasmodics are used during operations, massage, and some procedures to inhibit conduction. Very often, such funds are used in the rehabilitation period after surgical interventions and injuries.

The use of muscle relaxants is prohibited in the presence of the following indications:

• Pregnancy.
• lactation period.
• Renal, heart, liver failure.
• Epilepsy.
• Peptic ulcer, gastritis.
• Serious pathologies of the gastrointestinal tract.
• Parkinson's disease.
• Mental disorders.
• Alcoholism and drug addiction.
• Increased fatigue.
• Activities associated with increased attention and concentration.
• Children's age up to 3 years.

Classification

Antispasmodics are divided into 4 types, depending on the duration of the relaxing effect:

1. Ultrashort- relaxation occurs for no more than 7 minutes.
2. Short– the effect of relaxation lasts for 20 minutes.
3. Medium- spasm is removed for no more than 40 minutes.
4. Long– muscles relax for more than 40 minutes.

Depending on how muscle relaxants interact with receptors, 2 types of drugs are distinguished:

• Depolarizing- cause short-term chaotic contractions of muscle fibers, turning into relaxation. The effect of antispasmodics of this type is short-lived, mainly depolarizing drugs are used in surgical interventions.
• Non-depolarizing- do not cause depolarization.

By the nature of the effect, muscle relaxants are:

1. central impact- actively affect the central nervous system, help relieve spasms and relax muscles. They are used for many diseases characterized by the occurrence of spasms, the rehabilitation period after injuries and operations.
2. Peripheral exposure- affect the peripheral parts of the nervous system, quickly block the transmission of nerve impulses to muscle tissues. Most often used during operations. With degenerative - dystrophic diseases, they are almost inactive.

Overview of funds

The most effective muscle relaxants are drugs such as:

• Baclofen- affects the central nervous system, helps to relieve spasms, pain, eliminate convulsions. It is used for strokes, multiple sclerosis, traumatic brain injuries, cerebral palsy.
• "Baklosan"- has an antispasmodic and analgesic effect, reduces the tone of skeletal muscle tissue, inhibits the transmission of impulses to the muscles. It is used for craniocerebral injuries, paralysis, diseases of the spinal cord.
• "Tizanidin"- contains the active substance of the same name Tizanidin. The drug of central action, promotes relaxation and elimination of spasms of skeletal muscles. Indicated for use in degenerative diseases of the spine, lesions of the spinal cord and brain, neurological diseases, spasms that occur in the postoperative period. Does not affect voluntary movements.
• Sirdalud- a centrally acting muscle relaxant. Contains the active ingredient Tizanidin, which helps to relax skeletal muscles, eliminate increased tone and convulsions. It is used for lesions of the spinal cord, neurological diseases, acute muscle spasms. It is an analogue of the drug "Tizanidin". Does not affect voluntary movements.
• "Thezalud"- an analogue of "Sirdalud" and "Tizanidin", as it contains the same active ingredient Tizanidin. It is used for severe muscle spasms accompanied by pain, neurological pathologies, cerebrovascular accidents, in the postoperative period. Does not affect voluntary movements.
• "Mydocalm"- a drug that affects the central nervous system. Indications for use are diseases of the central nervous system, degenerative - dystrophic lesions of the joints, increased muscle tone, the rehabilitation period after surgical interventions, with violations of the innervation of blood vessels. Can be used by children from 1 year old.
• "Tolperil"- used for cerebral palsy, convulsions resulting from a stroke, increased muscle tone, diseases of the central nervous system, degenerative lesions of the spine and joints.
• "Meprobamat"- anticonvulsant, sedative, antispasmodic. Effective in diseases accompanied by increased muscle spasm, convulsions, joint pathologies, sleep disorders, mental illness. Is a tranquilizer.
• "Meprotan"- the drug has a muscle relaxant effect, reduces muscle tone, helps relieve nervous tension, eliminate insomnia, increased anxiety and other symptoms of mental disorders. Also used for convulsions. Is a tranquilizer.
• "Chlorzoxazon"- a muscle relaxant drug of central action. It is used for spasms of skeletal muscles, helps to eliminate hypertonicity and convulsions. Has an analgesic effect.
• "Pancuronium" is a non-depolarizing muscle relaxant. It blocks the conduction of electrical impulses from the nerve to the muscle, due to which muscle relaxation occurs. They are used only during operations for prolonged muscle relaxation.
• "Tubocurarine"- muscle relaxant drug of peripheral effects. It is used in surgical interventions, as well as in traumatology for the reduction of dislocations.
• "Ditilin"- affects the peripheral nervous system, blocks neuromuscular transmission. The action of the drug begins, on average, 50 seconds after intravenous administration, weakens all skeletal muscles.
• "Carisoprodol"- the action of the drug is based on blocking the transmission of nerve impulses from the nerves to the muscle. It is used for spasms and pain in muscle tissue, as well as for its damage. Most often it is used in physiotherapy and for injuries.
• "Dantrolene"- used for pathologies of the spinal cord, spinal injuries, neuropathy, osteochondrosis, stroke, muscle hypertonicity. The action is based on the blocking of neuromuscular transmission.

Application rules

In order for the effect of the use of antispasmodics to be maximum, they must be used in accordance with the rules:

1. Do not prescribe treatment on your own, only the attending specialist should prescribe it, based on the type of disease and the purpose of the appointment.
2. Use medications in accordance with the prescribed dosage and the number of uses per day.
3. The use of muscle relaxants should take place under the supervision of a physician, as these drugs have a large number of side effects.
4. Treatment begins with a low dose, gradually increasing it. It is forbidden to stop treatment abruptly, you need to gradually lower the dosage.
5. For a stronger effect, treatment with antispasmodics should be carried out in combination with massage, physiotherapy, exercise therapy.

If the drugs are used incorrectly, side effects such as weakness, headaches, nausea, decreased attention, insomnia, increased drowsiness, irritability, increased heart rate, problems with the liver and stomach can occur.