Local muscle relaxants. Poisoning with N-anticholinergics (curare-like) drugs

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

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

Mechanism of action of drugs

When severe pain occurs in the muscles, a spasm may occur, which ultimately limits movement in the joints, 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, treatment is extended indefinitely.

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

Considering the properties of muscle relaxants, we can say that they find their use at any stage of the treatment of osteochondrosis. The following procedures are more effective when using them:

Massage. Relaxed muscles respond best to stimulation.
Manual therapy. It's no secret that the doctor's influence is more effective and safer, the more relaxed the muscles are.
Physiotherapeutic procedures.
The effect of painkillers is enhanced.

If you often experience or suffer from osteochondrosis, then you should not prescribe muscle relaxants for yourself; 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 viewed from different points of view. If we talk about what muscle relaxants there are, there are different classifications. Analyzing the mechanism of action on the human body, we can distinguish only two types:

Peripheral acting drugs.
Central muscle relaxants.

Medicines can have effects of varying duration, depending on this they are:

Ultra-short action.
Short.
Average.
Long lasting.

Only a doctor can know exactly which drug is best for you in each specific 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, during convulsions, during paralysis during tetanus.

Muscle relaxants, peripherally acting drugs, can be divided into the following groups:

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

Centrally acting drugs

Muscle relaxants in this group can also be divided into the following types, taking into account their chemical composition:

Glycerol derivatives. These are Meprotan, Prenderol, Isoprotan.
Based on benzimidazole - "Flexin".
Mixed drugs, for example "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 medications not only relax, but have a broader effect, which is why they are used in the treatment of various diseases that are accompanied by increased muscle tone.

These muscle relaxants have virtually no effect on monosynaptic reflexes, so they can be used for relief without stopping natural breathing.

If you are prescribed muscle relaxants (drugs), you may come across the following names:

"Metacarbamol".
"Baclofen."
"Tolperisone".
"Tizanidine" 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:

Muscle relaxants should only be used when the patient is unconscious.
The use of such drugs significantly facilitates artificial ventilation.
Removing is not the most important thing, the main task is to carry out comprehensive measures to carry out gas exchange and maintain blood circulation.
If muscle relaxants are used during anesthesia, this does not exclude the use of anesthetics.

When drugs from this group became firmly established in medicine, we could safely talk about the beginning of a new era in anesthesiology. Their use made it possible to simultaneously solve several problems:

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

Area of application of muscle relaxants

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

In the treatment of neurological diseases that are accompanied by increased tone.
If you use muscle relaxants (drugs), the lower back pain will also subside.
Before surgery in the abdominal cavity.
During complex diagnostic procedures for certain diseases.
During electroconvulsive therapy.
When performing anesthesiology without stopping natural breathing.
To prevent complications after injuries.
Muscle relaxants (drugs) for osteochondrosis are often prescribed to patients.
To facilitate the recovery process after
The presence of an intervertebral hernia is also an indication for taking muscle relaxants.

Despite such an extensive list of uses for 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 may occur when taking these medications. Some are possible, but there are also more serious ones, among them the following are worth noting:

Decreased concentration, which is most dangerous for people driving a car.
Decreased blood pressure.
Increased nervous excitability.
Bed-wetting.
Allergic manifestations.
Problems with the gastrointestinal tract.
Convulsive states.

Especially often, all these manifestations can be diagnosed with the wrong dosage of drugs. This is especially true for anti-depolarizing 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 normalizes, and the use of medications to eliminate symptoms is not required.

You should be careful when taking muscle relaxants (drugs) whose names are unfamiliar to you. In this case, it is better to consult a doctor.

Contraindications for use

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

They should not be taken by people who have kidney problems.
Contraindicated for pregnant women and nursing mothers.
Psychological disorders.
Alcoholism.
Epilepsy.
Parkinson's disease.
Liver failure.
Children under 1 year of age.
Peptic ulcer disease.
Myasthenia.
Allergic reactions to the drug and its components.

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

Requirements for muscle relaxants

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

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

As a result of taking the drug, not only muscle tension is reduced, but its vasodilating effect is also observed. This is perhaps the only medicine 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 back pain, to which we try not to react. But there comes a time when the pain can no longer be ignored.

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

Since one of the symptoms of osteochondrosis is muscle spasm, it makes sense to talk about using 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 side effects, if any, can be immediately identified and a different medicine can be prescribed.

Almost all drugs are produced not only in the form of tablets, but there are also injections. Most often, in case of severe spasm and severe pain, the second form is prescribed for emergency assistance, that is, in the form of injections. The active substance penetrates 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, necessarily in combination with physiotherapeutic procedures, therapeutic exercises, and massage.

Despite their high effectiveness, you should not take these drugs without first consulting your doctor. You cannot independently determine which medicine is suitable for your case and will bring greater effect.

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

Drugs in this group primarily block the transmission of nerve impulses at the level of neuromuscular synapses of striated muscles. These include: tubocurarine chloride, diplacin, cyclobutonium, qualidil, anatruxonium, dioxonium, ditilin (listenone, myorelaxin), melliktin, condelfin. All of these are synthetic substances, with the exception of melliktin and condelfin - alkaloids from various types of larkspur.

There are drugs with depolarizing (ditilin) and competitive, anti-depolarizing (all other drugs) actions. Under the action of depolarizing curare-like agents, persistent depolarization of the end plates occurs, followed by relaxation of the skeletal muscles.

Antidepolarizing curare-like drugs block n-cholinergic receptors at neuromuscular synapses and thereby eliminate

the mediator functions of acetylcholine, which transfers excitation from the motor neuron to the skeletal muscle, which leads to relaxation of the latter.

Pathogenesis of poisoning. Ingestion of toxic doses of muscle relaxants, their overdose or increased sensitivity to them, including hereditary ones, cause paralysis of the respiratory intercostal muscles and diaphragm, resulting in asphyxia. Therefore, muscle relaxants during surgery are used only under intubation anesthesia and the presence of all the conditions necessary for controlled breathing. Inhalation drugs (ether, fluorotane), antibiotics (neomycin, streptomycin sulfate) can cause neuromuscular blockade, which should be taken into account when used together with muscle relaxants. The relaxing effect of the latter is enhanced by complications associated with drug overdose (anoxia, hypercapnia, acidosis), electrolyte imbalance (hypokalemia, hypocalcemia) and blood loss during anesthesia. Circulatory failure in the case of toxic effects of curare-like drugs is associated with hypotension and is usually secondary in nature due to developing respiratory depression. Curare-like drugs of antidepolarizing type of action are also characterized by a ganglion-blocking effect and the release of histamine from tissues, which in case of overdose can be an additional cause of a hypotonic state.

Depending on the relaxation mechanism, the approach to the treatment of poisoning with curare-like drugs is different. In case of overdose of antidepolarizing agents, the use of anticholinesterase agents, which increase the concentration of acetylcholine in the area of the end plates, is a method of antidote therapy. In case of poisoning with depolarizing agents, the use of the same drugs can increase the phenomena of depolarization and lead to a deepening of the neuromuscular block.

Diplacin. In relatively large quantities it does not interfere with blood circulation. When administered intravenously in doses of 3-4 mc/kg, the drug causes complete muscle relaxation and apnea within 5-6 minutes. The duration of the last one is 20-25 minutes. After breathing is restored, muscle relaxation lasts for a long time. With repeated administration, the effect increases, so the dose should be reduced by 1/3-1/2 of the original. The antidote for diplacin, although not always quite effective, is prozerin.

Ditilin- a short-term muscle relaxant, as it is easily hydrolyzed in the body by the enzyme butyrylcholine sterase in the blood serum. In case of malignant diseases and liver diseases, accompanied by a decrease in the production of this enzyme, with often occurring congenital hypocholine-esterasemia, increased sensitivity to dithiline is noted. This is also observed in kidney diseases, which impairs the release of dithiline.

With a single intravenous administration of the drug at a dose of 0.2-0.3 mg/kg body weight (1-2 ml of 1% solution) after 1-1.5 minutes the maximum effect can occur (without stopping breathing) lasting up to 3-7 minutes . If ditilin is administered in doses of 1-1.7 mg/kg, complete muscle relaxation and apnea lasting 5-7 minutes occurs. To obtain longer-term muscle relaxation, you can use drip or fractional administration. In this case, the mechanism of action may change - the depolarization block is replaced by a competitive one. As a result, in case of an overdose of dithiline after prolonged or repeated use, nroserine can be used cautiously as an antagonist.

Symptoms of poisoning are: heaviness of the eyelids, diplopia, difficulty speaking and swallowing, paralytic condition of the muscles of the limbs, neck, intercostal and, last of all, the diaphragm. Breathing is shallow, intermittent, rapid, with a pause after exhalation and inhalation. In case of overdose, severe bradycardia may occur with a sharp decrease in blood pressure.

First aid and treatment. When breathing is switched off, controlled breathing with oxygen must be used immediately. For the purpose of decurarization, when prescribing antidepolarizing agents (diplacin, etc.), 3 ml of a 0.05% solution of proserin is administered intravenously against a background of 0.5-1 ml of a 0.1% solution of atropine sulfate. The latter is prescribed to limit stimulation by proserin of n-cholinergic receptors in muscles and autonomic nodes. The decurarizing effect of prozerin is enhanced by the intravenous administration of calcium chloride or gluconate (5-10 ml of a 5% solution).

Persistent hypotension is eliminated by intravenous administration of sympathomimetic amines (ephedrine hydrochloride, norepinephrine hydrotartrate).

If ditilin is overdosed, a transfusion of fresh blood or plasma is recommended to replenish butyrylcholinesterase reserves, as well as plasma replacement drugs. When repeated administration of large doses of a drug that has an antidepolarizing effect, some authors consider it advisable to use proserin.

Treatment of acute poisoning, 1982

N.V. ORGANON (Netherlands)

ATX: V03AB35 (Sugammadex)

Antidote for muscle relaxants

ICD: T48 Poisoning with drugs acting primarily on smooth and skeletal muscles and the respiratory system

Selective antidote for the muscle relaxants rocuronium bromide and vecuronium bromide. Sugammadex is a modified gamma-cyclodextrin, which is a compound that selectively binds rocuronium bromide and vecuronium bromide. It forms a complex with them in the blood plasma, which leads to a decrease in the concentration of the muscle relaxant that binds to nicotinic receptors at the neuromuscular synapse. This results in reversal of the neuromuscular blockade caused by rocuronium bromide or vecuronium bromide.
There was a clear dependence of the effect on the dose of sugammadex, which was administered at different periods of time and at different depths of neuromuscular conduction block. Sugammadex was administered in doses of 0.5 to 16 mg/kg both after a single administration of rocuronium bromide in doses of 0.6, 0.9, 1 and 1.2 mg/kg, or after administration of vecuronium bromide in a dose of 0.1 mg/kg, and after administration of maintenance doses of these muscle relaxants .
Sugammadex can be used at various times after administration of rocuronium bromide or vecuronium bromide.
Kidney failure. Two open-label clinical studies compared the efficacy and safety of sugammadex in patients with or without severe renal impairment undergoing surgery. In one study, sugammadex was administered to reverse blockade caused by rocuronium bromide in the presence of 1-2 post-tetanic responses (4 mg/kg; n =68); in another study, sugammadex was administered at the onset of the second response at T2 (2 mg/kg; n=30). Recovery of neuromuscular conduction after blockade was not significantly longer in patients with severe renal failure compared to patients without renal failure. There were no cases of residual neuromuscular blockade or its resumption in patients with severe renal failure in these studies.
Effect on QTc interval. In three clinical studies of sugammadex used alone or in combination with rocuronium bromide or vecuronium bromide, or in combination with propofol or sevoflurane, no clinically significant increase in the QT/QTc interval was observed.

Indications

The pharmacokinetic parameters of sugammadex are calculated based on the summation of the concentrations of free sugammadex and sugammadex as part of the sugammadex-muscle relaxant complex. Pharmacokinetic parameters such as clearance and Vd are considered the same...

Contraindications

- severe renal failure (KK - severe liver failure;
- pregnancy;
- period of breastfeeding;
- children under 2 years of age;
- hypersensitivity to the components of the drug.

Dosage

Sugammadex should only be administered by or under the direction of an anesthesiologist. To monitor the degree of neuromuscular blockade and restoration of neuromuscular conduction, it is recommended to use an appropriate monitoring method. According to generally accepted...

Overdose

To date, there has been one report of an accidental overdose of the drug at a dose of 40 mg/kg. There were no significant side effects. Sugammadex is well tolerated in doses up to 96 mg/kg with the absence of any side effects...

Drug interactions

Interaction by binding type (hormonal contraceptives)
Due to the administration of sugammadex, the effectiveness of some drugs may be reduced due to a decrease in their (free) plasma concentration. In such a situation it is necessary...

Side effect

The following adverse reactions are most often (≥1/100 to 1/100) associated with the use of sugammadex.
Body system
Frequency of occurrence
Adverse reactions
Immune system disorder
Rarely (from ≥1/...

During pregnancy and breastfeeding

The use of sugammadex during pregnancy is not recommended due to insufficient data.
The excretion of sugammadex into milk in women during lactation has not been studied, but based on data from preclinical studies, this probability is not...

Use for liver dysfunction

Contraindicated in severe liver failure.

Use for renal impairment

Contraindicated in severe renal failure (CC Use in children Contraindicated in children under 2 years of age.

Use in elderly patients

Elderly patients: after the administration of sugammadex in the presence of 2 responses in the TOF stimulation mode against the background of blockade caused by rocuronium bromide, the full time of recovery of neuromuscular conduction (T4/T1 ratio up to 0.9) in adult patients...

Special instructions

Monitoring respiratory function during restoration of neuromuscular conduction
It is necessary to carry out mechanical ventilation until adequate spontaneous breathing is fully restored after elimination of the neuromuscular blockade. Even if there was a complete recovery...

Special conditions of admission

contraindicated in pregnancy, used with caution when breastfeeding, contraindicated in patients with impaired liver function, contraindicated in patients with impaired renal function, contraindicated in children, used with caution in elderly patients

Pharmacokinetics

Conditions for dispensing from pharmacies

The drug is available with a prescription.

Storage conditions

The drug should be stored out of the reach of children, protected from light, at a temperature of 2° to 8°C. Do not freeze. Shelf life - 3 years.

Release form

The solution for intravenous administration is transparent, colorless to light yellow.
1 ml
sugammadex sodium
108.8 mg,
which corresponds to the content of sugammadex
100 mg
Excipients: hydrochloric acid - q.s. up to pH 7....

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Muscle relaxants-medicines that reduce the tone of skeletal muscles with a decrease in motor activity up to complete immobility.

Mechanism of action - blockade of H-cholinergic receptors at synapses stops the supply of nerve impulses to skeletal muscles, and the muscles stop contracting. Relaxation comes from top to bottom, from facial muscles to the tips of the toes. The last thing to relax is the diaphragm. Conductivity restoration proceeds 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, tightly squeeze his hand and breathe independently for 10-15 minutes without signs of hypoxia. Objectively, the degree of influence of muscle relaxants is determined using the following methods: electromyography, accelomyography, peripheral neurostimulation, mechanomyography.

The duration of action of muscle relaxants is prolonged in the presence of the following factors: hypotension, hypoxia, hypercapnia, metabolic acidosis, hypovolemia, impaired microcirculation, hypokalemia, deep anesthesia, hypothermia, and elderly patient. The effect on M-cholinergic receptors of the heart, smooth muscle and vagus nerve depends on the drug and dose. Some muscle relaxants can trigger the release of histamine. They do not pass through the BBB. Passage through PB depends on the drug and dose. Insoluble in fats. Binding to blood proteins depends on the drug. The main route of administration is intravenous. They have no effect when taken as food, as they are highly polar.

1. Providing conditions for tracheal intubation. 2. Providing 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 when anticonvulsants are ineffective. 5. Blockade of protective reactions to cold in the form of muscle tremors and muscle hypertonicity during artificial hypothermia. 6. Myorelaxation during reposition of bone fragments and reduction of dislocations in joints where there are powerful muscle masses.

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

Substances of this group block H-cholinergic receptors located 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 neuromuscular block.

Classification:

1 - Muscle relaxants with antidepolarizing competitive action- substances that increase the concentration of ACh in the synaptic cleft, which competitively displaces the muscle relaxant from its connection with HX receptors and causes depolarization of the postsynaptic membrane, thereby restoring neuromuscular transmission. (alkaloid tubocurarine; drugs - curare-like)

a) benzylisoquinolines (tubocurarine, atracurium, mivacurium)

b) aminosteroids (pipecuronium, vecuronium, rocuronium)

Curare-like drugs are used to relax skeletal muscles during surgical operations. Under the influence 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 stops, the patient is transferred to artificial ventilation.

In addition, it is used to eliminate tonic convulsions in tetanus and strychnine poisoning. At the same time, relaxation of skeletal muscles helps eliminate cramps.

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

2 – Depolarizing muscle relaxants- Suxamethonium iodide (Ditylin, Lystenon, Miorelaxin) Suxamethonium iodide in its chemical structure is a double acetylcholine molecule.

Suxamethonium interacts with H-cholinergic receptors localized on the end plate of skeletal muscles, like acetylcholine, and causes depolarization of the postsynaptic membrane. At the same time, the muscle fibers contract, which manifests itself in the form of individual twitching of skeletal muscles - fasciculations. However, unlike acetylcholine, suxamethonium is resistant to acetylcholinesterase and therefore is practically not destroyed in the synaptic cleft. As a result, suxamethonium causes persistent depolarization of the postsynaptic endplate membrane.

Side effects: postoperative muscle pain (which is associated with microtrauma of the muscles during their fasciculations), respiratory depression (apnea), hyperkalemia and cardiac arrhythmias, hypertension, increased intraocular pressure, rhabdomyolysis and myoglobinemia, hyperthermia.

3 – Agents that reduce the release of ACh - Botox is a botulinum toxin type A drug that interferes with the release of ACh from the endings of cholinergic nerve fibers. The heavy chain of botulinum toxin has the ability to bind to specific receptors on nerve cell membranes. After binding to the presynaptic membrane of the nerve ending, botulinum toxin penetrates into the neuron by endocytosis.

Due to the fact that Botox prevents the release of ACh from the endings of sympathetic cholinergic fibers that innervate the sweat glands, the drug is used for hyperhidrosis to reduce the secretion of eccrine sweat glands (armpits, palms, feet). Injected intradermally. The effect lasts 6-8 months.

The drug is concentrated at the injection site for some time, and then enters the systemic circulation, does not penetrate the BBB and is quickly metabolized.

Side effects include pain and microhematomas at the injection site, slight general weakness for 1 week