Long-acting relaxants. Muscle relaxants. Pancuronium is a non-depolarizing muscle relaxant.

Relaxation of skeletal muscles can be caused by regional anesthesia, high doses of inhaled anesthetics, and drugs that block neuromuscular transmission (their common name is muscle relaxants). Muscle relaxants cause relaxation of skeletal muscles, but do not lead to loss of consciousness, amnesia and analgesia.

neuromuscular transmission.

A typical motor neuron consists of a cell body, many dendrites, and a single myelinated axon. The place where the motor neuron comes into contact with the muscle cell is called the neuromuscular junction. The cell membranes of the motor neuron and the muscle cell are separated by a narrow gap (20 nm) - the synaptic cleft. In the zone of the neuromuscular synapse, the axon loses its myelin sheath and takes on the form of characteristic protrusions. The axoplasm of these protrusions contains vacuoles filled with neuromuscular mediator acetylcholine (ACh). When ACh molecules are released, they diffuse through the synaptic cleft and interact with nicotine-sensitive cholinergic receptors (n-cholinergic receptors) of a specialized part of the muscle cell membrane - the end plate of the skeletal muscle.

Each cholinergic receptor consists of five protein subunits, two of which (a-subunits) are the same and are able to bind ACh molecules (one a-subunit - one binding site). If both subunits are occupied by ACh molecules, then the conformation of the subunits changes, which leads to a short-term (for 1 ms) opening of the ion channel passing through the thickness of the receptor.

Cations begin to flow through the open channel (sodium and calcium - from the outside into the cell, potassium - from the cell to the outside), which causes the appearance of the potential of the end plate.

If enough ACh receptors are occupied, then the total end plate potential becomes powerful enough to depolarize the postsynaptic membrane around the synapse. Sodium channels in this part of the muscle cell membrane open under the influence of a potential difference (in contrast to the channels in the end plate receptors, which open when exposed to ACh). The resulting action potential propagates along the membrane of the muscle cell and the T-tubule system, which causes the opening of sodium channels and the release of calcium ions from the cisterns of the sarcoplasmic reticulum. The released calcium mediates the interaction of the contractile proteins actin and myosin, which leads to the contraction of the muscle fiber.

The amount of released ACh usually greatly exceeds the minimum required for the development of an action potential. Some diseases disrupt the process of neuromuscular transmission: with myasthenic Eaton-Lambert syndrome, an insufficient amount of ACh is released, with myasthenia gravis, the number of cholinergic receptors is reduced.

The substrate-specific enzyme (specific cholinesterase) acetylcholinesterase rapidly hydrolyzes ACh into acetic acid and choline. As a result, the ion channels close, which leads to repolarization of the end plate. When the propagation of the action potential stops, the ion channels in the muscle fiber membrane also close. Calcium flows back into the sarcoplasmic reticulum and the muscle fiber relaxes.

Classification of muscle relaxants.

All muscle relaxants, depending on the mechanism of their action, are divided into two classes: depolarizing and non-depolarizing.

Savarese J. (1970) also proposed to divide all muscle relaxants depending on the duration of the neuromuscular block they cause: ultrashort action - less than 5-7 minutes, short action - less than 20 minutes, medium duration - less than 40 minutes and long action - more than 40 minutes.

Table number 1.

Mechanism of action of depolarizing muscle relaxants.

Depolarizing muscle relaxants, similar in structure to ACh, interact with n-cholinergic receptors and cause the action potential of the muscle cell. The effect of depolarizing muscle relaxants (succinylcholine, listenone, dithylin) is due to the fact that they act on the postsynaptic membrane like ACh, causing its depolarization and stimulation of the muscle fiber. However, unlike ACh, depolarizing muscle relaxants are not hydrolyzed by acetylcholinesterase, and their concentration in the synaptic cleft does not decrease for a long time, which causes prolonged depolarization of the end plate.

Prolonged depolarization of the end plate leads to muscle relaxation. Muscle relaxation occurs as follows: a powerful potential depolarizes the postsynaptic membrane around the synapse. The subsequent opening of sodium channels is short-lived. After initial excitation and opening, the channels close. Moreover, sodium channels cannot open again until end plate repolarization has occurred. In turn, repolarization of the end plate is impossible as long as the depolarizing muscle relaxant is associated with cholinergic receptors. Since the channels in the membrane around the synapse are closed, the action potential dries up and the muscle cell membrane repolarizes, which causes muscle relaxation. Such a blockade of neuromuscular conduction is commonly called the 1st phase of the depolarizing block. So, depolarizing muscle relaxants act as agonists of cholinergic receptors.

Depolarizing muscle relaxants do not interact with acetylcholinesterase. From the region of the neuromuscular synapse, they enter the bloodstream, after which they undergo hydrolysis in the plasma and liver under the influence of another enzyme, pseudocholinesterase (nonspecific cholinesterase, plasma cholinesterase). This process proceeds very quickly, which is favorable: there are no specific antidotes.

Since in neuromuscular synapses acetylcholinesterase inhibitors increase the amount of available ACh that competes with depolarizing relaxants, they are not able to eliminate the depolarizing block. In fact, by increasing the concentration of available ACh in the neuromuscular synapse and reducing the activity of plasma pseudocholinesterase, acetylcholinesterase inhibitors increase the duration of the depolarizing block.

In all cases, even a single administration of depolarizing muscle relaxants, not to mention the administration of repeated doses, changes to one degree or another are found on the postsynaptic membrane when the initial depolarizing blockade is accompanied by a blockade of a non-depolarizing type. This is the 2nd phase of action ("double block") of depolarizing muscle relaxants. The mechanism of the 2nd phase of action is still not known. However, it is clear that phase 2 action may subsequently be abolished by anticholinesterase drugs and exacerbated by non-depolarizing muscle relaxants.

Features of the action of depolarizing muscle relaxants.

The only ultra-short acting drugs are depolarizing muscle relaxants. Basically, these are suxamethonium preparations - succinylcholine, listenone, dithylin, myorelaxin. Features of the neuromuscular block when administered are as follows:

Complete neuromuscular blockade occurs within 30-40 seconds. They are commonly used in an induction scheme for tracheal intubation.

The duration of the block is quite short, usually 4-6 minutes. Therefore, they are used for endotracheal intubation followed by a transition to non-depolarizing relaxants or for short-term manipulations (for example, bronchoscopy under general anesthesia), when fractional additional administration can be used to prolong myoplegia.

Depolarizing relaxants cause muscle twitches. They appear in the form of convulsive muscle contraction from the moment the relaxants are injected and subside after approximately 40 seconds. This phenomenon is associated with the simultaneous depolarization of most of the neuromuscular synapses. Muscle fibrillations can cause a number of negative consequences (postoperative muscle pain, potassium release), and therefore, the precurarization method (prior administration of small doses of non-depolarizing muscle relaxants) is used to prevent them.

Depolarizing relaxants increase intraocular pressure. Therefore, they should be used with caution in patients with glaucoma, and in patients with penetrating eye injury, their use should be avoided if possible.

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

Since depolarizing muscle relaxants in the body are decomposed by plasma cholinesterase, a qualitative or quantitative deficiency of this enzyme causes an excessive increase in block (frequency of occurrence 1: 3000).

With the introduction of depolarizing muscle relaxants, the second phase of action may occur (development of a non-depolarizing block), which in the clinic is manifested by an unpredictable increase in the block.

A significant disadvantage is the presence of a high histamine effect.

Depolarizing relaxants remain the drugs of choice for emergency or complicated tracheal intubation, but their negative effects force them to abandon their use and use non-depolarizing relaxants.

Mechanism of action of non-depolarizing muscle relaxants.

Associated with competition between non-depolarizing muscle relaxants and ACh for specific receptors (which is why they are also called competitive). As a result, the sensitivity of the postsynaptic membrane to the effects of ACh sharply decreases. As a result of the action of competitive relaxants on the neuromuscular synapse, its postsynaptic membrane, which is in a state of polarization, loses the ability to go into a state of depolarization, and, accordingly, the muscle fiber loses its ability to contract. That is why these drugs are called non-depolarizing.

Non-depolarizing muscle relaxants act as competitive antagonists.

Neuromuscular blockade caused by non-depolarizing relaxants can be stopped with the use of anticholinesterase drugs (neostigmine, prozerin): the normal process of ACh biodegradation is disrupted, its concentration in the synapse increases, and as a result, it competitively displaces the relaxant from its connection with the receptor. The time of action of anticholinesterase drugs is limited, and if the end of action occurs before the destruction and removal of the muscle relaxant, a re-development of the neuromuscular block (recurarization) is possible.

Non-depolarizing muscle relaxants (with the exception of mivacurium) are not hydrolyzed by either acetylcholinesterase or pseudocholinesterase. With a non-depolarizing block, the restoration of neuromuscular conduction is due to redistribution, partial metabolic degradation and excretion of non-depolarizing muscle relaxants or may be caused by exposure to specific antidotes - acetylcholinesterase inhibitors.

Features of the action of non-depolarizing muscle relaxants.

Non-depolarizing drugs include short, medium and long-acting drugs.

Non-depolarizing muscle relaxants have the following characteristic features:

They cause the onset of neuromuscular blockade within 1-5 minutes (depending on the type of drug and its dose), which is much slower compared to depolarizing drugs.

The duration of neuromuscular blockade, depending on the type of drug, ranges from 15 to 60 minutes.

The introduction of depolarizing relaxants is not accompanied by muscle fibrillations.

The end of the neuromuscular block with its complete recovery can be accelerated by the administration of anticholinesterase drugs, although the risk of recurarization remains.

One of the disadvantages of this group of drugs is cumulation. This effect is least pronounced in trakrium and nimbex.

Also, the disadvantages include the dependence of the characteristics of the neuromuscular block on the function of the liver and kidneys. In patients with dysfunction of these organs, the duration of the block and, especially, recovery can be significantly increased.

To characterize the neuromuscular block, indicators such as the onset of action of the drug (the time from the end of administration to the onset of a complete block), the duration of action (the duration of a complete block), and the recovery period (time to restore 95% of conductivity) are used. An accurate assessment of the above indicators is carried out on the basis of a myographic study with electrical stimulation. This division is rather arbitrary and, moreover, largely depends on the dose of the relaxant.

It is clinically important that the onset of action is the time after which tracheal intubation can be performed under comfortable conditions; block duration is the time after which repeated administration of a muscle relaxant is required to prolong myoplegia; the recovery period is the time when tracheal extubation can be performed and the patient is capable of adequate spontaneous breathing.

The division of muscle relaxants according to the duration of action is rather arbitrary. Since, in addition to the dose of the drug, the onset, duration of action and the period of recovery of neuromuscular conduction largely depend on many factors, in particular the metabolism of drugs, the characteristics of their excretion from the body, the functions of the liver, kidneys, etc.

Depolarizing muscle relaxants.

Succinylcholine.

Succinylcholine is the only non-depolarizing muscle relaxant currently used in the clinic.

Compound.

1 ampoule (5 ml) contains 100 mg of suxamethonium chloride in isotonic aqueous solution.

Structure.

Succinylcholine - consists of two interconnected molecules of acetylcholine. Structural similarity to ACh explains the mechanism of action, side effects, and metabolism of succinylcholine. Due to structural similarity, allergy to one muscle relaxant indicates a high risk of cross-allergy to other muscle relaxants.

Metabolism and excretion.

The rapid onset of action (within one minute) is due to low lipid solubility (all muscle relaxants are highly ionized and water-soluble compounds) and relative overdose during use (usually the drug is administered in excessively high doses before intubation).

After entering the bloodstream, the vast majority of succinylcholine under the influence of pseudocholinesterase is rapidly hydrolyzed to succinylmonocholine. This reaction is so efficient that only part of the succinylcholine reaches the neuromuscular junction. After the concentration of the drug in the blood serum decreases, the molecules of succinylcholine begin to diffuse from the complex with cholinergic receptors into the bloodstream and neuromuscular conduction is restored. The duration of action of the drug is about 2 minutes with a complete cessation of action after 8-10 minutes.

The action of the drug is prolonged with increasing doses and metabolic disorders. The metabolism of succinylcholine is impaired by hypothermia, as well as by a low concentration or a hereditary defect in pseudocholinesterase. Hypothermia slows down hydrolysis. Serum pseudocholinesterase concentration (U/L) may decrease during pregnancy, liver disease, and under the influence of certain drugs.

Table No. 2. Drugs that reduce the concentration of pseudocholinesterase in serum.

In 2% of patients, one allele of the pseudocholinesterase gene is normal, the second is pathological (a heterozygous defect in the pseudocholinesterase gene), which somewhat prolongs the effect of the drug (up to 20-30 minutes). In 1 patient out of 3000, both alleles of the pseudocholinesterase gene are pathological (homozygous defect in the pseudocholinesterase gene), as a result of which the activity of pseudocholinesterase decreases by 100 times compared to the norm. In contrast to the reduced concentration and heterozygous defect of pseudocholinesterase, when the duration of the neuromuscular block increases only 2-3 times, with a homozygous defect, the neuromuscular block after the injection of succinylcholine lasts a very long time (up to 6-8 hours). Of the pathological pseudocholinesterase genes, the dibucaine variant is the most common.

Dibucaine is a local anesthetic that inhibits the activity of normal pseudocholinesterase by 80%, the activity of pseudocholinesterase in a heterozygous defect by 60%, and by 20% in a homozygous defect. The percentage of inhibition of pseudocholinesterase activity is called the dibucaine number. Dibucaine number is directly proportional to the functional activity of pseudocholinesterase and does not depend on its concentration. Therefore, to determine the activity of pseudocholinesterase in a laboratory study, the concentration of the enzyme is measured in units / l (a secondary factor determining activity) and its qualitative usefulness is determined - the dibucaine number (the main factor determining activity). With prolonged paralysis of skeletal muscles that occurs after the administration of succinylcholine to patients with pathological pseudocholinesterase (synonymous with atypical pseudocholinesterase), mechanical ventilation should be performed until neuromuscular conduction is fully restored. In some countries (but not in the US) heat-treated preparations of human plasma cholinesterase "Serumcholineseterase Behringwerke" are used. Although fresh frozen plasma can be used, the risk of infection usually outweighs the benefit of transfusion.

Interaction with drugs.

With regard to succinylcholine, the interaction with two groups of drugs is especially important.

A. Acetylcholinesterase inhibitors.

Although acetylcholinesterase inhibitors reverse the non-depolarizing block, they significantly prolong phase 1 of the depolarizing block. This phenomenon is explained by two mechanisms. First, the inhibition of acetylcholinesterase leads to an increase in the concentration of acetylcholine in the nerve terminal, which additionally stimulates depolarization. Secondly, these drugs inhibit the activity of pseudocholinesterase, which prevents the hydrolysis of succinylcholine. Phosphorus organic compounds, for example, cause irreversible inhibition of acetylcholinesterase, which prolongs the action of succinylcholine by 20-30 minutes.

B. Non-depolarizing muscle relaxants.

The introduction of non-depolarizing muscle relaxants in low doses before the injection of succinylcholine prevents the development of the 1st phase of the depolarizing block. Non-depolarizing muscle relaxants bind to cholinergic receptors, which partially eliminates the depolarization caused by succinylcholine. An exception is pancuronium, which enhances the action of succinylcholine due to the inhibition of pseudocholinesterase. If the dose of succinylcholine is high enough for the development of phase 2 of the depolarizing block, then the preliminary administration of a low dose of a non-depolarizing relaxant potentiates muscle relaxation. Similarly, administration of succinylcholine at a dose that allows tracheal intubation reduces the need for non-depolarizing muscle relaxants by at least 30 minutes.

Table No. 3. Interaction of muscle relaxants with other drugs: potentiation (+) and inhibition (-) of the neuromuscular block.

Dosage.

Because of its rapid onset and short duration of action, succinylcholine is considered by many anesthetists to be the drug of choice for routine adult tracheal intubation. Although rocuronium begins to act almost as quickly as succinylcholine, it causes a longer block.

The dosage depends on the desired degree of relaxation, on body weight and on the individual sensitivity of the patient. Based on this, it is recommended to determine the sensitivity to the drug before the start of the operation using a small test dose of 0.05 mg/kg IV.

The consequence of the introduction of 0.1 mg/kg is the relaxation of skeletal muscles without affecting the respiratory function, a dose of 0.2 mg/kg to 1.5 mg/kg leads to complete relaxation of the muscles of the abdominal wall and skeletal muscles and, further, to the limitation or complete cessation of spontaneous breathing.

In adults, the dose of succinylcholine required for tracheal intubation is 1-1.5 mg/kg intravenously. Fractional administration of succinylcholine in low doses (10 mg) or long-term drip administration (1 g per 500-1000 ml of solution), titrated by effect, is used in some surgical interventions that require short-term but pronounced myoplegia (for example, with endoscopy of ENT organs). To prevent an overdose of the drug and the development of a phase 2 depolarizing block, constant monitoring of neuromuscular conduction should be carried out using peripheral nerve stimulation. Maintaining muscle relaxation with succinylcholine has lost its former popularity with the advent of mivacurium, a short-acting, non-depolarizing muscle relaxant.

If intravenous injection is not possible, up to 2.5 mg/kg IM is prescribed, up to a maximum of 150 mg.

Succinylcholine is also used for tetanus in the form of a drip infusion of a 0.1% solution of 0.1-0.3 mg / min with simultaneous abundant access of oxygen. At the appropriate rate of administration, spontaneous breathing is maintained in full.

Since succinylcholine is not lipid soluble, its distribution is restricted to the extracellular space. The proportion of extracellular space per kilogram of body weight is greater in neonates and infants than in adults. Therefore, the dose of succinylcholine in children is higher compared to that in adults. With the / m administration of succinylcholine in children, even a dose of 4-5 mg / kg does not always achieve complete muscle relaxation. In children, intravenous doses are used: > 1 year - 1-2 mg / kg,<1 года- 2-3 мг/кг. Инфузия: 7.5 мг/кг/час

Prior administration of non-depolarizing muscle relaxants (precurarization) reduces or prevents the occurrence of side reactions of succinylcholine. Non-depolarizing relaxants are used at a dose of 1/5 of the main dose for intubation, then an analgesic, then succinylcholine.

Contraindications.

Hypersensitivity to suxamethonium chloride. Severe liver dysfunction, pulmonary edema, severe hyperthermia, low cholinesterase, hyperkalemia. Neuromuscular diseases and neurological disorders, muscle stiffness. Severe injuries and burns, penetrating eye damage. It is not recommended for use in patients with uremia, especially those with high serum potassium levels.

Succinylcholine is contraindicated in children and adolescents due to the high risk of rhabdomyolysis, hyperkalemia, and cardiac arrest in children with unrecognized myopathy.

.

Succinylcholine is a relatively safe drug - provided its many side effects are clearly understood and avoided.

A. Cardiovascular system.

Succinylcholine stimulates not only n-cholinergic receptors of the neuromuscular synapse - it stimulates all cholinergic receptors. Stimulation of n-cholinergic receptors of parasympathetic and sympathetic ganglia, as well as muscarinic cholinergic receptors (m-cholinergic receptors) of the sinoatrial node in the heart leads to an increase or decrease in blood pressure and heart rate.

The metabolite of succinylcholine, succinylmonocholine, stimulates the m-cholinergic receptors of the sinoatrial node, which causes bradycardia. Although children are particularly susceptible to this effect, adults also develop bradycardia after a second dose of succinylcholine. For the prevention of bradycardia, atropine is administered in doses in children - 0.02 mg / kg IV, in adults - 0.4 mg IV. sometimes succinylcholine causes nodal bradycardia and ventricular extrasystoles.

B. Fasciculations.

With the introduction of succinylcholine, the onset of muscle relaxation is indicated by contractions of motor units visible to the eye, which are called fasciculations. Fasciculations can be prevented by prior administration of a low dose of non-depolarizing muscle relaxants. Since this interaction prevents the development of phase 1 depolarizing block, high doses of succinylcholine (1.5 mg/kg) are required.

B. Hyperkalemia.

With the introduction of succinylcholine, depolarization leads to the fact that potassium is released from healthy muscles in an amount sufficient to increase the concentration in serum by 0.5 mEq / l. With a normal concentration of potassium, this phenomenon has no clinical significance, but in some conditions (burns, extensive injuries, some neurological diseases, etc.), the resulting hyperkalemia can be life-threatening.

Table No. 4. Conditions in which there is a high risk of developing hyperkalemia, combined with the use of succinylcholine

Subsequent cardiac arrest is often refractory to standard resuscitation measures: calcium, insulin, glucose, bicarbonate, dantrolene, and sometimes artificial circulation are required to reduce the concentration of potassium and eliminate metabolic acidosis. If an injury causes denervation (for example, with a complete transverse rupture of the spinal cord, many muscle groups undergo denervation), then cholinergic receptors are formed on the muscle membranes outside the neuromuscular synapse, which, when succinylcholine is administered, causes an all-encompassing muscle depolarization and a powerful release of potassium into the bloodstream. Pre-administration of a non-depolarizing muscle relaxant does not interfere with the prevention of potassium release and does not eliminate the threat to life. The risk of hyperkalemia peaks 7-10 days after injury, but the exact timing of the risk period is not known.

G. Pain in the muscles.

Succinylcholine increases the incidence of myalgia in the postoperative period. Complaints of muscle pain most often occur in young women after outpatient surgical interventions. During pregnancy, as well as in childhood and old age, the frequency of myalgia decreases.

D. Increased pressure in the cavity of the stomach.

Fasciculation of the muscles of the anterior abdominal wall increases the pressure in the lumen of the stomach, which in turn leads to an increase in the tone of the lower esophageal sphincter. Therefore, these two effects are mutually exclusive, and succinylcholine does not seem to increase the risk of gastric reflux and aspiration. The preliminary administration of a non-depolarizing muscle relaxant prevents both an increase in pressure in the gastric lumen and a compensatory increase in the tone of the lower esophageal sphincter.

E. Increased intraocular pressure.

The muscles of the eyeball differ from the rest of the striated muscles in that they contain many end plates on each cell. The administration of succinylcholine causes prolonged membrane depolarization and contraction of the muscles of the eyeball, which increases intraocular pressure and can damage the injured eye. The preliminary administration of a non-depolarizing muscle relaxant does not always prevent an increase in intraocular pressure.

G. Malignant hyperthermia.

Succinylcholine is a powerful trigger for malignant hyperthermia, a hypermetabolic disease of the skeletal muscles. An early symptom of malignant hyperthermia is often a paradoxical contraction of the jaw muscles after the administration of succinylcholine.

I. Prolonged paralysis of skeletal muscles.

At a low concentration of normal pseudocholinesterase, the administration of succinylcholine causes a moderate lengthening of the depolarizing block.

Temporary decrease in serum cholinesterase: severe liver disease, severe anemia, starvation, cachexia, dehydration, hyperthermia, acute poisoning, continuous use of pharmaceuticals containing cholinesterase inhibitors (phospholine, demecarium, neostigmine, physostigmine, distigmine) and drugs containing substances like succinylcholine (procaine IV).

After the administration of succinylcholine to patients with pathological pseudocholinesterase, prolonged paralysis of skeletal muscles occurs. In the absence of adequate respiratory support, this complication is a serious hazard.

K. Increased intracranial pressure.

In some patients, the administration of succinylcholine causes EEG activation, a moderate increase in cerebral blood flow and intracranial pressure. Maintenance of airway patency and mechanical ventilation in the mode of moderate hyperventilation weakens the increase in intracranial pressure. An increase in intracranial pressure can also be prevented by the administration of a non-depolarizing muscle relaxant and injection of lidocaine (1.5-2.0 mg/kg) 2-3 minutes before intubation. Tracheal intubation increases intracranial pressure significantly more than succinylcholine.

Compatibility with other drugs.

Preliminary administration of succinylcholine enhances the effect of non-depolarizing muscle relaxants. Prior administration of non-depolarizing muscle relaxants reduces or prevents the occurrence of adverse reactions of succinylcholine. Side effects associated with circulatory disorders increase when taking halogenated drugs (halothane), weaken when taking thiopental and atropine. The muscle relaxant effect of succinylcholine is enhanced by antibiotics such as aminoglycosides, amphotericin B, cyclopropane, propanidide, quinidine. Succinylcholine enhances the effect of digitalis preparations (risk of arrhythmias). Simultaneous infusion of blood or plasma weakens the effect of succinylcholine.

Non-depolarizing muscle relaxants.

Pharmacological characteristics.

Table number 5.

Pharmacology of non-depolarizing muscle relaxants.

Note. Beginning of action: + - slow; ++-moderately fast; +++-fast.

Duration of action: + - drug of short action; ++-drug of medium duration of action; +++ is a long-acting drug.

Histamine release: 0-absent; + - insignificant; ++-medium intensity; +++ significant.

Vagus nerve block: 0-absent; + - insignificant; ++-medium degree.

2 Based on the average wholesale price per 1 ml of the drug, which does not in all cases reflect the strength and duration of action.

The choice of a non-depolarizing muscle relaxant depends on the individual properties of the drug, which are largely determined by its structure. For example, steroid compounds have a vagolytic effect (i.e., suppress the function of the vagus nerve), and benzoquinolines release histamine from mast cells.

A. Influence on the autonomic nervous system.

Non-depolarizing muscle relaxants in clinical doses have different effects on n- and m-cholinergic receptors. Tubocurarine blocks the autonomic ganglia, which reduces the increase in heart rate and myocardial contractility mediated by the sympathetic nervous system in arterial hypotension and other types of operational stress. Pancuronium, on the contrary, blocks the m-cholinergic receptors of the sinoatrial node, which causes tachycardia. When used at recommended doses, atracurium, mivacurium, doxacurium, vecuronium and pipecuronium do not have a significant effect on the autonomic nervous system.

B. Release of histamine.

Histamine release from mast cells can cause bronchospasm, skin erythema, and hypotension due to peripheral vasodilation. The degree of histamine release is represented as follows: tubocurarine > methocurine > atracurium and mivacurium. The slow rate of administration and prior use of H1 and H2 blockers eliminate these side effects.

B. Hepatic clearance.

Only pancuronium and vecuronium are extensively metabolized in the liver. The main route of excretion of vecuronium and rocuronium is through the bile. Liver failure prolongs the action of pancuronium and rocuronium, but has a weaker effect on vecuronium. Atracurium and mivacurium undergo extensive extrahepatic metabolism.

D. Renal excretion.

Elimination of methocurine is almost entirely dependent on renal excretion, so this drug is contraindicated in renal insufficiency. However, methocurine is ionized, so it can be removed by hemodialysis. Tubocurarine, doxacurium, pancuronium, vecuronium, and pipecuronium are only partially eliminated by the kidneys, so renal insufficiency prolongs their action. Elimination of atracurium and mivacurium is independent of renal function.

D. Possibility of application for tracheal intubation.

Only rocuronium causes neuromuscular blockage as quickly as succinylcholine. The development of the effect of non-depolarizing muscle relaxants can be accelerated by using them in high or saturating doses. Although a high dose accelerates the onset of muscle relaxation, at the same time it exacerbates side effects and increases the duration of action.

The emergence of medium-acting drugs (atracurium, vecuronium, rocuronium) and short-acting drugs (mivacurium) led to the emergence of a method of administering muscle relaxants in two doses using a loading dose. Theoretically, the introduction of 10-15% of the standard dose for intubation 5 minutes before the induction of anesthesia causes blockade of a significant number of n-cholinergic receptors, so that subsequent injection of the remaining dose quickly causes muscle relaxation. A loading dose generally does not cause clinically significant skeletal muscle paralysis because it requires 75-80% blockade of the receptors (the neuromuscular margin of safety). However, in some cases, a loading dose blocks a sufficiently large number of receptors, which leads to shortness of breath and dysphagia. In this case, the patient must be calmed and the induction of anesthesia should be carried out quickly. In respiratory failure, a loading dose can significantly impair respiratory function and reduce the amount of oxyhemoglobin. The loading dose allows tracheal intubation 60 seconds after the main dose of rocuronium and 90 seconds after the main dose of the other medium-acting muscle relaxants. Rocuronium is the non-depolarizing muscle relaxant of choice for rapid sequential induction due to rapid onset of muscle relaxation, few side effects even at high doses, and moderate duration of action.

E. Fasciculations.

To prevent fasciculations, 10-15% of the standard dose of a non-depolarizing muscle relaxant for intubation (precurarization) is administered 5 minutes before succinylcholine. For this purpose, most non-depolarizing muscle relaxants can be used, the most effective of which is tubocurarine. Since non-depolarizing muscle relaxants are phase 1 antagonists of the depolarizing block, the dose of succinylcholine should be high (1.5 mg/kg).

G. Potentiating effect of inhalation anesthetics.

Inhalation anesthetics reduce the need for non-depolarizing muscle relaxants by at least 15%. The degree of potentiation depends both on the anesthetic used (isoflurane, sevoflurane, desflurane and enflurane > halothane > nitrous oxide/oxygen/opiate) and on the relaxant used (tubocurarine and pancuronium > vecuronium and atracurium).

Z. Potentiating effect of other non-depolarizing muscle relaxants.

The combination of some non-depolarizing muscle relaxants (for example, tubocurarine and pancuronium) does not cause an additive effect, but a potentiating one. An additional advantage of some combinations is the reduction of side effects: for example, pancuronium weakens the hypotensive effect of tubocurarine. The lack of potentiation in the interaction of muscle relaxants with a similar structure (for example, vecuronium and pancuronium) gave rise to the theory that potentiation occurs as a result of minor differences in the mechanism of action.

Influence of some parameters on the pharmacological properties of non-depolarizing muscle relaxants.

A. Temperature.

Hypothermia lengthens the neuromuscular block due to inhibition of metabolism (eg, mivacurium, atracurium) and slow excretion (tubocurarine, methocurine, pancuronium).

B. Acid-base balance.

Respiratory acidosis potentiates the action of most non-depolarizing muscle relaxants and inhibits the restoration of neuromuscular conduction by acetylcholinesterase inhibitors. Consequently, hypoventilation in the postoperative period prevents the complete restoration of neuromuscular conduction.

B. Electrolyte disorders.

Hypokalemia and hypocalcemia potentiate non-depolarizing block. The effect of hypercalcemia is unpredictable. Hypermagnesemia, which can occur during the treatment of preeclampsia with magnesium sulfate, potentiates non-depolarizing block due to competition with calcium in the skeletal muscle end plates.

D. Age.

Newborns have an increased sensitivity to muscle relaxants due to the immaturity of neuromuscular synapses. However, this hypersensitivity does not necessarily cause a decrease in the need for muscle relaxants - a large extracellular space in newborns increases the volume of distribution.

D. Interaction with drugs.

See table number 3.

E. Concomitant diseases.

Diseases of the nervous system and muscles have a profound effect on the action of muscle relaxants.

Table No. 6. Diseases in which the response to non-depolarizing muscle relaxants changes.

Liver cirrhosis and chronic renal failure often increase the volume of distribution and decrease the plasma concentration of water-soluble drugs such as muscle relaxants. At the same time, the duration of action of drugs, the metabolism of which depends on hepatic and renal excretion, increases. Thus, in case of liver cirrhosis and chronic renal failure, it is advisable to use a higher initial dose of muscle relaxants and a lower maintenance dose (compared to standard conditions).

G. The reaction of various muscle groups.

The onset of muscle relaxation and its duration varies widely in different muscle groups. This variability may be due to uneven blood flow, different distances to large vessels, and unequal fiber composition. Moreover, the relative sensitivity of muscle groups varies with different muscle relaxants. With the introduction of non-depolarizing muscle relaxants in the diaphragm, muscles of the larynx and in the circular muscle of the eye, muscle relaxation occurs and disappears faster than in the muscles of the thumb. In this case, the diaphragm can contract even in the complete absence of the reaction of the abductor thumb muscle to stimulation of the ulnar nerve. The muscles of the glottis may be resistant to the action of muscle relaxants, which is often observed during laryngoscopy.

Many factors influence the duration and depth of muscle relaxation, therefore, to assess the effect of muscle relaxants, it is desirable to monitor neuromuscular conduction. The recommended doses are indicative and require adjustment depending on individual sensitivity.

tubocurarine.

Structure.

Tubocurarine (d-tubocurarine) is a monoquaternary ammonium compound containing a tertiary amino group. The quaternary ammonium group mimics the positively charged region of the ACh molecule and is therefore responsible for binding to the receptor, while the large annular part of the molecule prevents receptor stimulation.

Metabolism and excretion.

Tubocurarine is not extensively metabolized. Elimination occurs mainly through the kidneys (50% of the drug is excreted in the first 24 hours) and, to a lesser extent, with bile (10%). The presence of renal failure prolongs the action of the drug.

Dosage.

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.

In children, the need for a loading dose is not lower, while the intervals between the administration of maintenance doses of the drug are longer. Neonatal sensitivity to tubocurarine varies considerably.

Tubocurarine is released at 3 mg in 1 ml of solution. Store at room temperature.

Side effects and application features.

Occur primarily due to the release of histamine. The effect of tubocurarine on autonomic ganglia plays a minor role.

B. Bronchospasm.

Caused by the release of histamine. Tubocurarine should not be used in bronchial asthma.

Metocurine.

Structure.

Metocurine is a bis-quaternary derivative of tubocurarine. The similarity of many pharmacological characteristics and side effects of tubocurarine and methocurine is due to structural analogy.

Metabolism and excretion.

Like tubocurarine, methocurine is not metabolized and is excreted mainly through the kidneys (50% of the drug in the first 24 hours). the presence of renal failure prolongs the action of the drug. Excretion with bile plays a minor role (<5%).

Dosage.

Intubation is possible with the introduction of the drug at a dose of 0.3 mg / kg. Slow administration over 1-2 minutes minimizes side effects. The loading dose for intraoperative muscle relaxation is 0.08 mg/kg, the maintenance dose is 0.03 mg/kg.

Features of the use of tubocurarine in pediatrics apply to the use of methocurine. Regardless of age, the power of methocurine is 2 times higher than that of tubocurarine.

Side effects and application features.

The introduction of methocurine in doses equivalent to those of tubocurarine causes the release of half the amount of histamine. Nevertheless, with the introduction of high doses, arterial hypotension, tachycardia, bronchospasm and allergic reactions occur. Allergy to iodine (which is, for example, with an allergy to fish) is a contraindication for use. Because the drug contains iodine.

Atracurium (Trakrium).

Release form.

Ampoules 2.5 ml: each ampoule contains 25 mg of atracurium besilate in the form of a clear, pale yellow solution.

Ampoules 5 ml: each ampoule contains 50 mg of atracurium besilate in the form of a clear, pale yellow solution.

Structure.

Atracurium contains a quaternary ammonium group. At the same time, the benzoquinoline structure of atracurium ensures the metabolism of the drug.

Metabolism and excretion.

The metabolism of atracurium is so intense that its pharmacokinetics does not depend on the state of liver and kidney function: less than 10% of the drug is excreted unchanged in the urine and bile. Metabolism is provided by two independent processes.

A. Hydrolysis of the ester bond.

This process is catalyzed by nonspecific esterases, and acetylcholinesterase and pseudocholinesterase are not related to it.

B. Elimination of Hoffman.

At physiological pH (about 7.40) and body temperature, atracurium undergoes spontaneous non-enzymatic chemical degradation at a constant rate, so that the half-life of the drug is about 20 minutes.

None of the resulting metabolites has the properties of a muscle relaxant, and therefore atracurium does not accumulate in the body.

Dosage and application.

Injection in adults:

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. Complete block can be prolonged by additional injections of trakrium at 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 non-muscular conduction occurs after about 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.

Use in adults as an infusion:

After an initial bolus dose of 0.3-0.6 mg/kg to maintain neuromuscular blockage during long-term surgery, atracurium can be administered by continuous infusion at a rate of 0.3-0.6 mg/kg/h (or 5-10 mcg/kg´ min). With this rate, the drug can be administered during coronary artery bypass grafting. Artificial hypothermia of the body to 25-26ºС reduces the rate of atracurium inactivation, therefore, at such low temperatures, a complete neuromuscular block can be maintained by reducing the infusion rate by about half.

Use in the intensive care unit:

After an initial dose of 0.3-0.6 mg/kg, Trakrium can be used to maintain myoplegia by continuous infusion at a rate of 11-13 µg/kg´ min (0.65-0.78 mg/kg/h). However, the doses vary greatly from patient to patient. Dose requirements may change over time. In patients of intensive care units, the rate of spontaneous recovery of neuromuscular conduction after Trakrium infusion does not depend on its duration. Trakrium is compatible with the following infusion solutions:

Infusion solution Stability period

Sodium chloride for IV administration 0.9% 24 hours

Glucose solution 5% 8 hours

Application in children:

In children older than 1 month, Trakrium is used in the same doses as in adults, based on body weight.

Use in elderly patients:

In elderly patients, Trakrium is used in standard doses. It is recommended, however, to use the lowest initial dose and to slow the rate of administration of the drug.

Side effects and application features.

A. Arterial hypotension and tachycardia.

Side effects in relation to the circulatory system are rare, provided that the dose exceeds 0.5 mg / kg. Atracurium is also capable of causing a transient decrease in peripheral vascular resistance and an increase in cardiac index independent of histamine release. It does not have a clinically significant effect on heart rate and is not contraindicated in bradycardia associated with the use of a number of anesthetics or vagal stimulation during surgery. The slow rate of administration of the drug reduces the severity of these side effects.

B. Bronchospasm.

Atracurium should not be used in bronchial asthma. Moreover, atracurium can cause severe bronchospasm even if there is no history of asthma.

B. Laudanosine toxicity.

Laudanosine is a metabolic product of atracurium resulting from Hoffman elimination. Laudanosine excites the central nervous system, which increases the need for anesthetics (MAC increases) and even provokes convulsions. The severity of these effects in the vast majority of cases does not reach clinical significance; exceptions occur when using an excessively high total dose of the drug or hepatic insufficiency (laudanosine is metabolized in the liver).

D. Sensitivity to body temperature and pH.

Hypothermia and alkalosis inhibit Hoffman elimination, which prolongs the action of atracurium.

D. Chemical incompatibility.

If atracurium is administered into an IV infusion system containing an alkaline solution (eg, thiopental), it precipitates as an acid.

Pregnancy and lactation.

Trakrium should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus. Trakrium can be used to maintain myoplegia during caesarean section, since when administered at recommended doses, it does not cross the placenta in clinically significant concentrations. It is not known if trakrium is excreted in breast milk.

Interaction with other drugs.

The neuromuscular block caused by trakrium may be aggravated by the use of inhaled anesthetics (such as halothane, isoflurane, enflurane), while the use of: antibiotics (aminoglycosides, polymyxin, tetracycline, lincomycin), antiarrhythmic drugs (propranolol, calcium channel blockers, lidocaine, procainamide, quinidine), diuretics (furosemide, mannitol, thiazide diuretics), magnesia, ketamine, lithium salts, ganglion blockers.

Additionally.

Trakrium does not affect intraocular pressure, which makes it convenient for use in eye surgery.

Hemofiltration and hemodiafiltration have minimal effect on plasma concentrations of atracurium and its metabolites, including laudanosine. The effect of hemodialysis and hemoperfusion on plasma concentrations of atracurium and its metabolites is unknown.

Cisatracurium (Nimbex).

Structure.

Cisatracurium is a non-depolarizing muscle relaxant that is an isomer of atracurium.

Metabolism and excretion.

At physiological pH and body temperature, cisatracurium, like atracurium, undergoes Hoffman elimination. As a result of this reaction, metabolites (monoquaternary acryulate and laudanosine) arise, which do not cause a neuromuscular block. Nonspecific esterases are not involved in the metabolism of cisatracurium. The presence of renal and hepatic insufficiency does not affect the metabolism and elimination of cisatracurium.

Dosage.

The dose for intubation is 0.1-0.15 mg/kg, administered over 2 minutes, which causes neuromuscular blockade of the average duration of action (25-40 minutes). Infusion at a dose of 1-2 mcg / (kg × min) allows you to maintain intraoperative muscle relaxation. Thus, cisatracurium is equally effective as vecuronium.

Cisatracurium should be stored in a refrigerator at 2-8°C. after removal from the refrigerator and storage at room temperature, the drug should be used within 21 days.

Side effects and application features.

Cisatracurium, unlike atracurium, does not cause a persistent dose-dependent increase in plasma histamine. Cisatracurium does not affect heart rate, blood pressure and the autonomic nervous system, even at a dose exceeding LD95 by 8 times.

The toxicity of laudanosine, sensitivity to body temperature and pH, and chemical incompatibility characteristic of atracurium are equally characteristic of cisatracurium.

Mivacurium (mivakron).

Structure.

Mivacurium is a benzoquinoline derivative.

Metabolism and excretion.

Mivacurium, like succinylcholine, is hydrolyzed by pseudocholinesterase. True cholinesterase takes an extremely small part in the metabolism of mivacurium. Therefore, if the concentration of pseudocholinesterase is reduced (Table No. 2) or it is represented by an atypical variant, then the duration of action of mivacurium will increase significantly. With a heterozygous defective pseudocholinesterase gene, the block lasts 2-3 times longer than usual, with a homozygous one, it can last hours. Since with a homozygous defect, pseudocholinesterase is not metabolized by mivacuria, the duration of the neuromuscular block becomes similar to that with the introduction of long-acting muscle relaxants. Unlike succinylcholine, acetylcholinesterase inhibitors eliminate the myoparalytic effect of mivacurium in the presence of at least a weak muscle response to nerve stimulation. Despite the fact that the metabolism of mivacurium does not directly depend on the state of liver or kidney function, the duration of its action in the presence of liver or kidney failure is increased due to a decrease in the concentration of pseudocholinesterase in plasma.

Dosage.

The dose required for intubation is 0.15-0.2 mg / kg; tracheal intubation can be carried out 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. Infusion in the initial dose of 4-10 mcg/(kg×min) allows for intraoperative muscle relaxation. 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.

Side effects and application features.

Mivacurium releases histamine quantitatively similar to atracurium. Slow administration of the drug (within 1 min) allows minimizing arterial hypotension and tachycardia due to the release of histamine. However, if the dose of mivacurium exceeds 0.15 mg/kg, then in heart disease, even a slow administration of the drug does not prevent a sharp decrease in blood pressure. Beginning of action 2-3 min. The main advantage of mivacurium is a short duration of action (20-30 min), which is 2-3 times longer than phase 1 of the succinylcholine block, but two times shorter than the duration of action of atracurium, vecuronium and rocuronium. In children, the drug begins to act faster and the duration is shorter than in adults.

To date, mivacurium is the muscle relaxant of choice for one-day hospital operations and endoscopic surgery. It can also be recommended for operations with unpredictable duration.

Doxacurium.

Structure.

Doxacurium is a benzoquinoline compound similar in structure to mivacurium and atracurium.

Metabolism and excretion.

This powerful long-acting muscle relaxant is only slightly hydrolyzed by plasma cholinesterase. As with other long-acting muscle relaxants, the main route of elimination is via the kidneys. In the presence of kidney disease, the duration of action of doxacurium increases. Bile excretion does not play a significant role in the elimination of doxacurium.

Dosage.

The dose required for intubation is 0.03-0.05 mg/kg. Intubation can be performed 5 minutes after injection. The loading dose for intraoperative muscle relaxation is 0.02 mg/kg, maintenance fractional doses are 0.005 mg/kg. The doses of doxacurium for children and the elderly in terms of body weight are similar to those mentioned above, although in old age doxacurium lasts longer. Doxacurium is not used in newborns, because. contains benzyl alcohol, which can cause fatal neurological complications.

Side effects and application features.

Doxacurium does not release histamine and does not affect blood circulation. It begins to act slightly slower than other long-acting non-depolarizing muscle relaxants (after 4-6 minutes), while the duration of the effect is similar to that of pancuronium (60-90 minutes).

Pancuronium (pavulon).

Release form.

The active substance of pavulon is pancuronium bromide. Each ampoule of pavulon contains 4 mg of pancuronium bromide in 2 ml of a sterile aqueous solution.

Structure.

Pancuronium consists of a steroid ring to which two modified acetylcholine molecules (a bis-quaternary ammonium compound) are attached. Pancuronium binds to the cholinergic receptor, but does not stimulate it.

Pharmacological properties.

Does not have hormonal activity.

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. The time of onset of action at a dose of 0.06 mg/kg is approximately 5 minutes, and the duration of action from the moment of administration until the restoration of 25% of muscle contractions is approximately 35 minutes, until the restoration of 90% of contractions is 73 minutes. Higher doses cause a decrease in the time of onset of action and increase the duration.

Metabolism and excretion.

Pancuronium is partially metabolized in the liver (deacetylation). One of the metabolites has about half the activity of the parent drug, which may be one of the reasons for the cumulative effect. Excretion occurs mainly through the kidneys (40%), to a lesser extent with bile (10%). Naturally, in the presence of renal insufficiency, the elimination of pancuronium slows down and the neuromuscular block lengthens. With cirrhosis of the liver, due to an increased volume of distribution, it is necessary to increase the initial dose, but the maintenance dose is reduced due to low clearance.

Dosage.

Recommended doses for intubation: 0.08-0.1 mg/kg. Good conditions for intubation are provided within 90-120 seconds after the intravenous administration of a dose of 0.1 mg/kg of body weight and within 120-150 seconds after the administration of 0.08 mg/kg of pancuronium.

When intubating with succinylcholine, it is recommended to use pancuronium at a dose of 0.04-0.06 mg/kg.

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

In children, the dose of pancuronium is 0.1 mg/kg, additional injections are 0.04 mg/kg.

Side effects and application features.

A. Arterial hypertension and tachycardia.

Pancuronium causes minor cardiovascular effects, manifested as a moderate increase in heart rate, blood pressure and cardiac output. The effect of pancuronium on blood circulation is due to blockade of the vagus nerve and the release of catecholamines from the endings of adrenergic nerves. Pancuronium should be used with caution in cases where the development of tachycardia is an increased risk factor (IHD, hypertrophic cardiomyopathy), in the case of the use of pavulon in dosages exceeding the recommended ones, when using vagolytic agents for premedication or during induction anesthesia.

B. Arrhythmias.

An increase in atrioventricular conduction and the release of catecholamines increase the likelihood of ventricular arrhythmias in patients at risk. The risk of arrhythmia is especially high with the combination of pancuronium, tricyclic antidepressants and halothane.

B. Allergic reactions.

In case of hypersensitivity to bromides, an allergy to pancuronium (pancuronium bromide) may occur.

G. Influence on intraocular pressure.

Pancuronium causes a significant (20%) decrease in normal or elevated intraocular pressure a few minutes after administration, and also causes miosis. This effect can be used to lower intraocular pressure during laryngoscopy and endotracheal intubation. The use of pancuronium in ophthalmic surgery may also be recommended.

D. Use during pregnancy and lactation.

Pancuronium is used in cesarean section operations, because. pavulon slightly penetrates the placental barrier, which is not accompanied by any clinical manifestations in newborns.

Interaction with other drugs.

Enlargement effect: anesthetics (halothane, enflurane, isoflurane, thiopental, ketamine, fentanyl, etomidate), other non-depolarizing muscle relaxants, pre-administration of succinylcholine, other drugs (antibiotics - aminoglycosides, metronidazole, penicillin, diuretics, MAO inhibitors, quinidine, protamine, a-blockers, magnesium salts).

Reducing effect: neostigmine, amidopyridine derivatives, prior long-term administration of corticosteroids, phenytoin, or carbamazepine; norepinephrine, azathioprine, theophylline, KCl, CaCl 2.

Vecuronium (norcuron).

Structure.

Vecuronium is pancuronium without a quaternary methyl group (i.e. it is a monoquaternary ammonium compound). A slight structural difference reduces the severity of side effects without affecting the potency.

Metabolism and excretion.

To a small extent, the metabolism of vecuronium occurs in the liver. One of the metabolites of vecuronium (3-OH metabolite) has pharmacological activity, and the cumulative qualities of the drug may be associated with it. Vecuronium is excreted mainly in the bile, to a lesser extent through the kidneys (25%). Vecuronium is advisable to use in renal failure, although sometimes this condition prolongs the effect of the drug. The short duration of action of vecuronium is explained by the shorter elimination half-life and faster clearance compared to pancuronium. Long-term use of vecuronium in intensive care units causes prolonged neuromuscular blocking (up to several days) in patients, possibly due to accumulation of the 3-hydroxy metabolite or due to the development of polyneuropathy. Risk factors include being female, having kidney failure, long-term use of corticosteroids, and sepsis. The action of vecuronium is prolonged in AIDS. With prolonged use, tolerance to the drug develops.

Dosage.

Vecuronium is equally effective as pancuronium. The dose required for intubation is 0.08-0.1 mg/kg; tracheal intubation can be performed in 1.5-2.5 minutes. The loading dose for intraoperative muscle relaxation is 0.04 mg/kg, the maintenance dose is 0.1 mg/kg every 15-20 minutes. Infusion at a dose of 1-2 mcg / (kg × min) also allows you to achieve good muscle relaxation. The duration of action of the drug at normal dosages is about 20-35 minutes, with repeated administration - up to 60 minutes.

Age does not affect loading dose requirements, while intervals between maintenance doses in neonates and infants should be longer. The duration of action of vecuronium increases in women who have just given birth due to changes in hepatic blood flow and absorption of the drug by the liver.

Vecuronium is packaged in 10 mg powder form, which is dissolved in preservative-free water immediately before administration. The diluted preparation can be used within 24 hours.

Side effects and application features.

A. Blood circulation.

Even at a dose of 0.28 mg/kg, vecuronium does not affect blood circulation.

B. Liver failure.

Although the elimination of vecuronium is determined by biliary excretion, the presence of hepatic insufficiency does not significantly increase the duration of action of the drug - provided that the dose does not exceed 0.15 mg / kg. In the anhepatic phase of liver transplantation, the need for vecuronium is reduced.

Pipecuronium (Arduan).

Compound.

1 bottle contains 4 mg of lyophilized pipecuronium bromide and 1 ampoule of solvent contains 2 ml of 0.9% sodium chloride.

Structure.

Pipecuronium is a bisquaternary ammonium compound with a steroid structure very similar to pancuronium.

Metabolism and excretion.

As with other long-acting non-depolarizing muscle relaxants, metabolism plays a minor role in the elimination of pipecuronium. Elimination is determined by excretion, which occurs mainly through the kidneys (70%) and bile (20%). The duration of action is increased in patients with renal but not hepatic insufficiency.

Action.

The time to the development of the maximum effect and the duration depends on the dose. Measured by a peripheral nerve stimulator, 95% blockade in 2-3 minutes after administration of succinylcholine, while without succinylcholine in 4-5 minutes. For a 95% neuromuscular blockade after the use of succinylcholine, 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.

Termination of the effect: at 80-85% blockade, the effect of pipecuronium can be quickly and reliably stopped by the administration of anticholinesterases together with atropine.

Dosage.

Pipecuronium is slightly more powerful than pancuronium. The dose for intubation is 0.04-0.08 mg/kg, the optimal conditions for intubation occur in 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 with the cumulation of the 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. In children, the need for the drug is the same. Old age has little effect on the pharmacology of pipecuronium.

Side effects and application features.

The main advantage of pipecuronium over pancuronium is the absence of side effects on blood circulation. Pipecuronium does not cause histamine release. The onset and duration of these drugs are similar.

Rocuronium (Esmeron).

Structure.

This monoquaternary steroid analogue of vecuronium has been synthesized in such a way as to provide a rapid onset of action.

Metabolism and excretion.

Rocuronium is not metabolized and is eliminated mainly in the bile and, to a lesser extent, through the kidneys. The duration of action increases in patients with hepatic insufficiency, while the presence of renal insufficiency does not have a special effect on the pharmacology of the drug.

Dosage.

The power of rocuronium is lower than that of other steroidal muscle relaxants (power is inversely proportional to the speed of onset of the effect). 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). The duration of action of rocuronium in elderly patients is significantly increased.

Side effects and application features.

Rocuronium (at a dose of 0.9-1.2 mg/kg) is the only non-depolarizing muscle relaxant that begins to act as quickly as succinylcholine, making it the drug of choice for rapid sequential induction. The average duration of action of rocuronium is similar to that of vecuronium and atracurium. Rocuronium produces a slightly more pronounced vagolytic effect than pancuronium.

Decreasing the tone of skeletal muscles with a decrease in motor activity up to complete immobilization.

Encyclopedic YouTube

1 / 3

✪ Basic pharmacology of muscle relaxants of peripheral action

✪ Muscle relaxants | Blockade of trigger points | Trigger Point Injection

✪ Anticholinergics. M and N-cholinergic blockers.

Subtitles

general characteristics

The mechanism of action - the blockade of H-cholinergic receptors in the synapses stops the supply of a nerve impulse to the skeletal muscles, and the muscles stop contracting. Relaxation goes from bottom to top, from the tips of the toes to the facial muscles. The diaphragm relaxes last. Conductivity is restored in the reverse order. The first subjective sign of the end of muscle relaxation is the patient's attempts to breathe on his own. Signs of complete decurarization: the patient can raise and hold his head for 5 seconds, hold his hand tightly and breathe on his own for 10-15 minutes without signs of hypoxia.

Objectively, the degree of exposure to muscle relaxants is determined using the following methods: electromyography, accelomyography, peripheral neurostimulation, mechanomyography.

The time of action of muscle relaxants is prolonged in the presence of such factors: hypotension, hypoxia, hypercapnia, metabolic acidosis, hypovolemia, impaired microcirculation, hypokalemia, deep anesthesia, hypothermia, the patient's advanced age.

General indications for the use of muscle relaxants

2. Ensuring muscle relaxation during surgical interventions to create optimal working conditions for the surgical team without excessive doses of drugs for general anesthesia, as well as the need for muscle relaxation during some diagnostic procedures performed under general anesthesia (for example, bronchoscopy).

3. Suppression of spontaneous breathing for the purpose of mechanical ventilation.

4. Elimination of convulsive syndrome with the ineffectiveness of anticonvulsants.

5. Blockade of protective reactions to cold in the form of muscle tremors and muscle hypertonicity during artificial hypothermia.

6. Muscle relaxation during reposition of bone fragments and reduction of dislocations in the joints, where there are powerful muscle masses.

General contraindications to the use of muscle relaxants

4. Increased pressure inside the hollow organs and cavities of the body.

5. The release of potassium into the blood can lead to hyperkalemia, and that in turn to bradycardia and cardiac arrest.

Contraindications:

1. Patients with initial hyperkalemia (renal failure, extensive burns and muscle injury).

2. Patients with heart rhythm disorders.

3. Patients at risk of complications with increased ICP, increased pressure in the hollow organs of the gastrointestinal tract. Patients with glaucoma.

Preparations:

At the moment, due to possible complications, only listenone is used in the clinic, but it is gradually being replaced by short-acting non-depolarizing muscle relaxants.

Non-depolarizing muscle relaxants- block receptors and membrane channels without opening them, without causing depolarization. The duration of action and properties depend on the drug.

Anticholinesterase drugs block cholinesterase, the amount of acetylcholine increases and it competitively displaces a non-depolarizing muscle relaxant. Prozerin is used at a dose of 0.03-0.05 mg/kg of body weight. Atropine 0.1% 0.5 ml is administered 2-3 minutes before use to level the side effects of prozerin. intravenously. Decurarization is contraindicated in deep muscle block and any disturbance of water and electrolyte balance. If the effect of prozerin ends earlier than the effect of the muscle relaxant, then recurarization- the resumption of muscle relaxation due to the activation of cholinesterase and a decrease in the amount of acetylcholine in the synaptic cleft.

In medicine, quite often there are situations when it is necessary to relax muscle fibers. For these purposes, they are introduced into the body, they block neuromuscular impulses, and the striated muscles relax.

Medicines of this group are often used in surgery, to relieve convulsions, before repositioning a dislocated joint, and even during exacerbations of osteochondrosis.

The mechanism of action of drugs

With severe pain in the muscles, a spasm may occur, as a result, movement in the joints is limited, which can lead to complete immobility. This issue is especially acute in osteochondrosis. Constant spasm interferes with the proper functioning of muscle fibers, and, accordingly, the treatment is stretched indefinitely.

To bring the patient's general well-being back to normal, muscle relaxants are prescribed. Preparations for osteochondrosis are quite capable of relaxing muscles and reducing the inflammatory process.

Given the properties of muscle relaxants, we can say that they find their application at any stage of the treatment of osteochondrosis. The following procedures are more effective in their application:

• Massage. Relaxed muscles respond best to exposure.
• Manual therapy. It's no secret that the effect of a doctor is the more effective and safer, the more relaxed the muscles.
• Physiotherapy procedures.
• The effect of painkillers is enhanced.

If you often experience or suffer from osteochondrosis, then you should not prescribe muscle relaxants on your own, drugs in this group should only be prescribed by a doctor. The fact is that they have a fairly extensive list of contraindications and side effects, so only a doctor can choose a medicine for you.

Classification of muscle relaxants

The division of drugs in this group into different categories can be considered from different points of view. If we talk about what muscle relaxants are, there are different classifications. Analyzing the mechanism of action on the human body, only two types can be distinguished:

1. Peripheral drugs.
2. Central muscle relaxants.

Medicines can have a different effect in duration, depending on this, they distinguish:

• Ultra short action.
• short.
• Medium.
• Long.

Only a doctor can know exactly which drug is best for you in each case, so do not self-medicate.

Peripheral muscle relaxants

Able to block nerve impulses that pass to muscle fibers. They are widely used: during anesthesia, with convulsions, with paralysis during tetanus.

Muscle relaxants, drugs of peripheral action, can be divided into the following groups:

All of these drugs affect cholinergic receptors in skeletal muscles, and therefore are effective for muscle spasms and pain. They act quite gently, which allows them to be used in various surgical interventions.

Central acting drugs

Muscle relaxants of this group can also be divided into the following types, given their chemical composition:

1. Derivatives of glycerin. These are Meprotan, Prenderol, Isoprotan.
2. Based on benzimidazole - "Flexin".
3. Mixed drugs, such as Mydocalm, Baclofen.

Central muscle relaxants are able to block reflexes that have many synapses in muscle tissue. They do this by reducing the activity of interneurons in the spinal cord. These drugs not only relax, but have a wider effect, which is why they are used in the treatment of various diseases that are accompanied by increased muscle tone.

These muscle relaxants have practically no effect on monosynaptic reflexes, so they can be used to remove and not turn off natural breathing.

If you are prescribed muscle relaxants (drugs), you can find the following names:

• "Metacarbamol".
• "Baclofen".
• "Tolperizon".
• "Tizanidin" and others.

It is better to start taking medications under the supervision of a doctor.

The principle of using muscle relaxants

If we talk about the use of these drugs in anesthesiology, we can note the following principles:

1. Muscle relaxants should be used only when the patient is unconscious.
2. The use of such drugs greatly facilitates artificial ventilation of the lungs.
3. It is not the most important thing to remove, the main task is to carry out comprehensive measures for the implementation of gas exchange and maintaining blood circulation.
4. If muscle relaxants are used during anesthesia, then this does not preclude the use of anesthetics.

When drugs of this group firmly entered medicine, one could safely talk about the beginning of a new era in anesthesiology. Their use allowed us to simultaneously solve several problems:

After the introduction of such drugs into practice, anesthesiology was able to become an independent industry.

Scope of muscle relaxants

Considering that substances from this group of drugs have an extensive effect on the body, they are widely used in medical practice. The following directions can be listed:

1. In the treatment of neurological diseases that are accompanied by increased tone.
2. If you use muscle relaxants (drugs), lower back pain will also recede.
3. Before surgery in the abdominal cavity.
4. During complex diagnostic procedures for certain diseases.
5. During electroconvulsive therapy.
6. When conducting anesthesiology without turning off natural breathing.
7. For the prevention of complications after injuries.
8. Muscle relaxants (drugs) for osteochondrosis are often prescribed to patients.
9. To facilitate the recovery process after
10. The presence of an intervertebral hernia is also an indication for taking muscle relaxants.

Despite such an extensive list of the use of these drugs, you should not prescribe them yourself, without consulting a doctor.

Side effects after taking

If you have been prescribed muscle relaxants (drugs), lower back pain should definitely leave you alone, only side effects can occur when taking these drugs. On some it is possible, but there are more serious ones, among them it is worth noting the following:

• Reduced concentration, which is most dangerous for people sitting behind the wheel of a car.
• Lowering blood pressure.
• Increased nervous excitability.
• Bed-wetting.
• allergic manifestations.
• Problems from the gastrointestinal tract.
• Convulsive conditions.

Especially often, all these manifestations can be diagnosed with the wrong dosage of drugs. This is especially true for antidepolarizing drugs. It is urgent to stop taking them and consult a doctor. Neostigmine solution is usually prescribed intravenously.

Depolarizing muscle relaxants are more harmless in this regard. When they are canceled, the patient's condition is normalized, and the use of medications to eliminate symptoms is not required.

You should be careful to take those muscle relaxants (drugs), the names of which are unfamiliar to you. In this case, it is better to consult a doctor.

Contraindications for use

Taking any medications should be started only after consulting a doctor, and these medications even more so. They have a whole list of contraindications, among them are:

1. They should not be taken by people who have kidney problems.
2. Contraindicated in pregnant women and nursing mothers.
3. Psychological disorders.
4. Alcoholism.
5. Epilepsy.
6. Parkinson's disease.
7. Liver failure.
8. Children's age up to 1 year.
9. Ulcer disease.
10. Myasthenia.
11. Allergic reactions to the drug and its components.

As you can see, muscle relaxants (drugs) have many contraindications, so you should not harm your health even more and start taking them at your own peril and risk.

Requirements for muscle relaxants

Modern drugs should not only be effective in relieving muscle spasm, but also meet certain requirements:

One of these drugs, which practically meets all the requirements, is Mydocalm. This is probably why it has been used in medical practice for more than 40 years, not only in our country, but also in many others.

Among the central muscle relaxants, it differs significantly from others for the better. This drug acts on several levels at once: it removes increased impulses, suppresses the formation in pain receptors, and slows down the conduction of hyperactive reflexes.

As a result of taking the drug, not only muscle tension decreases, but also its vasodilating effect is observed. This is perhaps the only drug that relieves spasm of muscle fibers, but does not cause muscle weakness, and also does not interact with alcohol.

Osteochondrosis and muscle relaxants

This disease is quite common in the modern world. Our lifestyle gradually leads to the fact that back pain appears, to which we try not to react. But there comes a point when the pain can no longer be ignored.

We turn to the doctor for help, but precious time is often lost. The question arises: "Is it possible to use muscle relaxants in diseases of the musculoskeletal system?"

Since one of the symptoms of osteochondrosis is muscle spasm, it makes sense to talk about the use of drugs to relax spasmodic muscles. During therapy, the following drugs from the group of muscle relaxants are most often used.

In therapy, it is usually not customary to take several drugs at the same time. This is provided so that you can immediately identify side effects, if any, and prescribe another medicine.

Almost all drugs are available not only in the form of tablets, but there are also injections. Most often, with severe spasm and severe pain syndrome, the second form is prescribed for emergency care, that is, in the form of injections. The active substance penetrates into the blood faster and begins its therapeutic effect.

Tablets are usually not taken on an empty stomach, so as not to harm the mucous membrane. You need to drink water. Both injections and tablets are prescribed to be taken twice a day, unless there are special recommendations.

The use of muscle relaxants will only bring the desired effect if they are used in complex therapy, a combination with physiotherapy, therapeutic exercises, and massage is mandatory.

Despite their high effectiveness, you should not take these drugs without first consulting with your doctor. You can't decide for yourself which medicine is right for you and will have the best effect.

Do not forget that there are a lot of contraindications and side effects that should not be discounted either. Only competent treatment will allow you to forget about pain and spasmodic muscles forever.

Drugs that block neuromuscular synapses cause relaxation of skeletal muscles (muscle relaxation) due to blockade of the transmission of nerve impulses from motor nerves to muscles.

Depending on the mechanism of the neuromuscular block, there are

Muscle relaxants with antidepolarizing (non-depolarizing) action

Depolarizing muscle relaxants.

Muscle relaxants of antidepolarizing (non-depolarizing) action.

Substances of this group block H-cholinergic receptors localized on the end plate of skeletal muscles and prevent their interaction with acetylcholine, as a result of which acetylcholine does not cause depolarization of the muscle fiber membrane - the muscles do not contract. This condition is called a neuromuscular block. However, with an increase in the concentration of acetylcholine in the synaptic cleft (for example, when using anticholinesterase

means) acetylcholine competitively displaces the muscle relaxant from its connection with the H-cholinergic receptor and causes depolarization of the postsynaptic membrane - neuromuscular transmission is restored. Substances that act in this way are called muscle relaxants of antidepolarizing competitive action.

Antidepolarizing muscle relaxants mainly belong to two chemical groups:

Benzylisoquinolines (tubocurarine, atracurium, mivacurium);

Aminosteroids (pipecuronium, vecuronium, rocuronium).

Depending on the duration of the neuromuscular block they cause, drugs are isolated:

Long-acting (30 minutes or more) - tubocurarine, pipecuronium;

Average duration of action (20-30 min) - atracurium, vecuronium, rocuronium;

Short-acting (10 min) - mivacurium.

Curare-like agents are used to relax skeletal muscles during surgical operations. Under the action of curare-like drugs, the muscles relax in the following sequence: first, the muscles of the face, larynx, neck, then the muscles of the limbs, torso, and lastly the respiratory muscles - breathing stops. When breathing is turned off, the patient is transferred to artificial lung ventilation.

In addition, curariform drugs are used to eliminate tonic convulsions in tetanus and in strychnine poisoning. At the same time, relaxation of the skeletal muscles helps to eliminate convulsions.

Side effects of some curare-like drugs (tubocurarine, atracurium, mivacurium) are mainly related to their ability to release histamine. It can cause hypotension, bronchospasm, reddening of the skin, and, less commonly, other anaphylactoid reactions. To a greater extent, the release of histamine is promoted by tubocurarine.

Antagonists of muscle relaxants of antidepolarizing action are anticholinesterase agents. By inhibiting the activity of acetylcholinesterase, they prevent the hydrolysis of acetylcholine and thus increase its concentration in the synaptic cleft. Acetylcholine displaces the drug from its association with H-cholinergic receptors, which leads to the restoration of neuromuscular transmission. Anticholinesterase agents (particularly neostigmine) are used to interrupt the neuromuscular block or eliminate residual effects after administration of antidepolarizing muscle relaxants.

Depolarizing muscle relaxants.

Suxamethonium causes persistent depolarization of the postsynaptic membrane of the end plate. This leads to neuromuscular

transmission and relaxation of skeletal muscles. At the same time, acetylcholine released into the synaptic cleft only enhances the depolarization of the membrane and deepens the neuromuscular block.

Suxamethonium is used for tracheal intubation, endoscopic procedures (broncho-, esophago-, cystoscopy), short-term operations (suturing the abdominal wall, reduction of dislocations, reposition of bone fragments), to eliminate tonic convulsions in tetanus.

After intravenous administration of suxamethonium, its myoparalytic effect begins after 30 s-1 min, and lasts up to 10 min. Such a short-term effect of the drug is associated with its rapid destruction by plasma pseudocholinesterase (choline and succinic acid are formed). With a genetic deficiency of this enzyme, the action of suxamethonium can last up to 2-6 hours. The muscle relaxant effect of the drug can be stopped by transfusion of fresh citrated blood, which contains active pseudocholinesterase.

Side effects: postoperative muscle pain (which is associated with muscle microtrauma during their fasciculations), respiratory depression (apnea), hyperkalemia and cardiac arrhythmias, hypertension, increased intraocular pressure, rhabdomyolysis and myoglobinemia, hyperthermia. Suxamethonium is contraindicated in glaucoma, liver dysfunction, anemia, pregnancy, malignant hyperthermia, in infancy.

adrenomimetic agents. Classification. Influence of adrenaline on the cardiovascular system, smooth muscles, metabolism. Norepinephrine and other adrenomimetics. Indications for use.

Adrenomimetics subdivided into:

a) α-agonists(means that predominantly stimulate α-adrenergic receptors);

Mezaton (a,) Naphthyzine (a 2)

Galazolin (a 2)

b) β-agonists (means that mainly stimulate β-adrenergic receptors);

Isadrin (b1, b2)

Dobutamine (b1)

Salbutamol (b2)

Fenoterol (b2)

Terbutaline (b2)

c) a-, β-adrenomimetics(drugs that stimulate α- and β-adrenergic receptors).

Adrenaline hydrochloride (or hydrogen tartrate)

Norepinephrine Hydrotartrate

By stimulating β-adrenergic receptors of the heart, adrenalin increases the strength and frequency of heart contractions and, in connection with this, the stroke and minute volume of the heart. This increases myocardial oxygen consumption. Systolic blood pressure rises. The pressor response usually causes reflex bradycardia.

Adrenaline dilates the pupils (due to contraction of the radial muscle of the iris of the eye

Adrenaline has a pronounced effect on the smooth muscles of the internal organs. By stimulating the β-adrenergic receptors of the bronchi, it relaxes the smooth muscles of the latter and eliminates bronchospasm. The tone and motility of the gastrointestinal tract under the influence of adrenaline are reduced (due to the excitation of a- and p-adrenergic receptors), sphincters are toned (a-adrenergic receptors are stimulated). The sphincter of the bladder also contracts.

With the introduction of adrenaline, the capsule of the spleen is reduced.

It has a beneficial effect on neuromuscular transmission, especially against the background of muscle fatigue. This is associated with an increase in the release of acetylcholine from the presynaptic endings, as well as with the direct action of adrenaline on the muscle.

Adrenaline increases the secretion of the salivary glands (thick, viscous saliva is released).

Adrenaline has a characteristic effect on metabolism. It stimulates glycogenolysis (hyperglycemia occurs, the content of lactic acid and potassium ions increase in the blood) and lipolysis (an increase in the content of free fatty acids in the blood plasma due to the release of fat depots).

Under the influence of adrenaline on the central nervous system, the effects of excitation predominate. It is expressed to a small extent.

When administered orally, adrenaline is destroyed (in the gastrointestinal tract and liver). In this regard, it is used parenterally (subcutaneously, intramuscularly, and sometimes intravenously) and topically. Adrenaline acts for a short time (with intravenous administration - about 5 minutes, with subcutaneous injection - up to 30 minutes), since its rapid neuronal uptake occurs, as well as enzymatic cleavage with the participation of COMT and partly MAO.

Adrenaline is used for anaphylactic shock and some other immediate allergic reactions. It is also effective as a bronchodilator for the relief of asthma attacks. It is also used for hypoglycemic coma caused by antidiabetic drugs (insulin, etc.). Sometimes it is prescribed as a pressor substance (norepinephrine and mezaton are more often used for these purposes). Adrenaline is added to anesthetic solutions (see chapter I; 1.1). Vasoconstriction in the injection area of ​​adrenaline enhances local anesthesia and reduces the resorptive and possible toxic effects of anesthetics. Adrenaline can be used to eliminate atrioventricular block, as well as in case of cardiac arrest (administered intracardially). It is used in ophthalmology for pupil dilation and in open-angle glaucoma.

Adrenaline can lead to heart rhythm disturbances. The most pronounced arrhythmias (in particular, ventricular extrasystoles) with the introduction of adrenaline with substances that sensitize the myocardium to it (for example, against the background of the action of the halothane anesthesia agent).

NORADRENALIN.

The main effect of norepinephrine is a pronounced, but short-lived (within a few minutes) increase in blood pressure associated with its effect on a-adrenergic receptors of blood vessels and an increase in peripheral resistance of the latter. Unlike adrenaline, a subsequent decrease in blood pressure is usually not observed, since norepinephrine has very little effect on B 2 -adrenergic receptors in blood vessels. Veins under the influence of norepinephrine narrow.

The rhythm of heart contractions against the background of the action of norepinephrine is reduced. Sinus bradycardia occurs as a result of reflex influences from the vascular mechanore-peptors in response to rapidly onset hypertension. The efferent pathways are the vagus nerves. In this regard, bradycardia to norepinephrine can be prevented by the administration of atropine. Reflex mechanisms largely neutralize the stimulating effect of noradrenaline on P,-adrenergic receptors of the heart. As a result, cardiac output (minute volume) remains practically unchanged or even decreases, while stroke volume increases.

On the smooth muscles of the internal organs, metabolism and the central nervous system, norepinephrine has a unidirectional effect with adrenaline, but in terms of the severity of these effects it is significantly inferior to it.

When administered orally, norepinephrine is destroyed (in the gastrointestinal tract and liver). When administered subcutaneously, it causes vasospasm at the injection site and therefore is poorly absorbed and can cause tissue necrosis. The main route is the intravenous route of its administration. After a single injection, norepinephrine acts for a short time, so it is injected into a vein by drip. The rate of intravenous infusion is determined by the increase in blood pressure to the desired level. In the body, norepinephrine is quickly inactivated due to the mechanisms already noted (neuronal uptake, enzymatic transformations). Metabolites and a small part of unchanged norepinephrine are excreted by the kidneys.

Norepinephrine is used in many conditions accompanied by an acute decrease in blood pressure (trauma, surgery).

In cardiogenic and hemorrhagic shock with severe hypotension, norepinephrine is not recommended, since the spasm of arterioles caused by it further worsens the blood supply to tissues. In these cases, a-blockers and, possibly, p-adrenomimetics can give a positive effect; blood substitutes are used to increase blood pressure.

Side effects with the use of norepinephrine are rare. Respiratory disorders, headache, cardiac arrhythmias are possible when combined with substances that increase myocardial excitability. Consideration should be given to the possibility of tissue necrosis at the injection site of norepinephrine. This is due to the ingress of the latter into the surrounding tissues and spasm of arterioles. The introduction of norepinephrine into a vein through a catheter, the use of heating pads, changing injection sites, and other measures reduce the possibility of such a complication.

Osteochondrosis is characterized by a significant overstrain of the muscles in the area where the structure of the intervertebral discs is disturbed, as well as the mixing of the vertebrae. This results in significant pain. Muscle relaxants are commonly used drugs in the treatment of osteochondrosis, which help to relax muscles.

Muscle relaxants are used in the presence of muscle spasm, as they help to immobilize damaged muscles and eliminate their excessive activity.

Muscle relaxant preparations are used only according to the doctor's indications. Similar drugs are presented in two different groups that have different effects on the patient's body. These can be drugs of peripheral and central effects. Medicamentous peripheral agents for osteochondrosis are ineffective, which is why they are often used in anesthesiology, traumatology and during surgery. These drugs blunt the conduction of nerve impulses to muscle tissue.

Important! Only the doctor determines the need for the use of a certain group of muscle relaxants, in connection with the existing indications and contraindications.

With osteochondrosis, it is imperative to quickly relieve muscle spasm and reduce pain, therefore drugs of a central effect are required.

Indication for use

Muscle relaxants are widely used in the presence of osteochondrosis for complex therapy, since such drugs themselves do not have any therapeutic effect at all. Relaxing all muscle groups, they allow you to regularly carry out other therapeutic manipulations, in particular:

• massage;
• gymnastics;
• manual therapy.

You should not use muscle relaxants for self-medication, since such drugs have many different contraindications and side effects, which is why only the attending doctor should prescribe them. Often, these types of drugs are used if, due to the course of osteochondrosis, there is a restriction in movement and intense painful manifestations. They are appointed if necessary to supplement the action of NSAIDs. If there are contraindications to the use of NSAIDs, muscle relaxants are prescribed to replace them and eliminate painful manifestations and muscle spasm for subsequent therapy.

Operating principle

In the process of ongoing pathological disorders provoked by osteochondrosis, the patient's intervertebral discs and vertebrae are destroyed and the normal functioning of muscle fibers is disrupted. In this regard, a muscle spasm appears, accompanied by acute pain and restricting the movement of a person.

That is why, during therapy, along with anti-inflammatory and analgesic drugs, muscle relaxants are widely used. These drugs help reduce muscle tension, so that it is possible to quickly eliminate pain. However, in order to fully restore the mobility of the damaged area, it is recommended to take muscle relaxants for several weeks, depending on the severity of the pathology.

The most popular names of muscle relaxants used for the treatment of osteochondrosis:

They help not only to relieve excessive muscle strain, but also further enhance the effect of ongoing physiotherapy. That is why physiotherapy procedures, carried out in combination with the use of muscle relaxants, help speed up the recovery process.

Muscle relaxants are selected only by a doctor, and their dosage is calculated according to the available indicators after a comprehensive diagnosis. Basically, the full course of therapy for osteochondrosis usually ranges from 3 to 7 days, depending on the severity of the course of the disease and the intensity of the painful syndrome that has arisen.

Mydocalm is considered one of the most popular drugs, as it is well tolerated by the patient's body and has the required therapeutic effect. It contains the active active ingredient - tolperisone, and also contains lidocaine, which helps to eliminate pain. The use of Mydocalm allows you to reduce the dosage of anti-inflammatory drugs and analgesics.

Sirdalud helps to eliminate muscle spasms and is used in acute and chronic disease. Baclofen is well tolerated by patients and the drug is used for severe pain. The use of Baclofen during complex therapy can significantly reduce the treatment time. Muscle relaxants are quite effective in complex therapy, however, their use is strictly limited due to the presence of many side effects.

Side effects

Patients suffering from osteochondrosis are prescribed muscle relaxants of central action during complex therapy. The doctor first evaluates the need for their use, taking into account the possibility of side effects. In particular, side effects include:

• muscle weakness;
• headache;
• decrease in concentration;
• dry mouth;
• convulsions;
• disorders of the nervous system;
• problems with the liver, stomach, heart.

In addition, patients may experience allergies, drowsiness, sleep disturbance, depression, hallucinations. Due to the presence of a large number of side effects, such drugs are used for therapy only in a hospital or at home, but under the constant supervision of a doctor. At the time of taking the medicine, it is necessary to exclude activities that require increased attention, and it is also forbidden to drive a car.

Muscle relaxants are not prescribed for admission for a long time, as negative reactions of the body may occur. In addition, they provoke addiction, and the patient's weight may increase slightly.

Contraindications

A feature of muscle relaxants is their almost instantaneous absorption by the stomach and intestines. Some of the drugs settle in the liver and are excreted along with the urine by the kidneys. The only exception is Baclofen, which is excreted unchanged.

The rapid absorption of muscle relaxants significantly increases the number of contraindications for their use. In particular, it is forbidden to use drugs in case of:

• renal failure;
• liver diseases;
• pregnancy;
• breastfeeding;
• allergies;
• ulcers;
• mental instability.

The use of muscle relaxants should not be interrupted abruptly, since there should be a gradual decrease in the dose of the drug taken and this happens over several weeks.