Long-acting ganglion blockers.
Ganglioblockers short acting.
Hygronia (Hygronium).
Application: in anesthesiology to create artificial hypotension. A 0.01% solution in an isotonic sodium chloride solution or a 5% glucose solution is administered intravenously (dropwise).
Side effects: severe hypotension.
Release form: powder 0.1 g in 10 ml ampoule No. 10. List B.
Benzohexonium (Benzohezonium).
Application: spasm peripheral vessels, hypertonic disease, hypertensive crises, bronchial asthma, peptic ulcer stomach and duodenum. Prescribed orally 0.1–0.2 g 2–3 times a day, subcutaneously, intramuscularly – 1–1.5 ml of a 2.5% solution. V.R.D. – orally 0.3 g; V.S.D. – 0.9 g; subcutaneous single dose – 0.075 g, daily – 0.3 g.
Side effects: general weakness, dizziness, palpitations, orthostatic collapse, dry mouth, bladder atony.
Contraindications: hypotension, severe liver and kidney damage, thrombophlebitis, severe changes in the central nervous system.
Release form: tablets of 0.1 g No. 20, ampoules of 1 ml of 2.5% solution No. 10.
Pentamin (Pentaminum).
Indications for use, side effects and contraindications: similar to benzohexonium.
Release form: in ampoules of 1 and 2 ml of 5% solution.
Pachycarpine hydroiodide (Pachycarpini hydroiodidum).
Application: for spasms of peripheral vessels and to stimulate labor, to reduce bleeding in postpartum period. Prescribed orally, subcutaneously, intramuscularly.
Contraindications: pregnancy, severe hypotension, liver and kidney diseases.
Release form: Available in tablets of 0.1 g, ampoules of 2 ml of 3% solution. Dispensed only with a doctor's prescription. List B. This group also includes pyrylene tablets ( Pirilenum) and temekhin ( Temechinum) 0.005 g.
Curare-like substances block n-cholinergic receptors of skeletal muscles and cause relaxation of skeletal muscles (muscle relaxants). According to their mechanism of action, they are divided into substances:
1) antidepolarizing (competitive) type of action (tubocurarine, diplacin, melictin);
2) depolarizing type of action (ditilin);
3) mixed type action (dioxonium).
According to the duration of action, muscle relaxants are divided into three groups:
1) short-acting (5–10 min) – dithilin;
2) medium duration (20–40 min) – tubocurarine chloride, diplacin;
3) long-acting (60 minutes or more) – anatruxonium.
Tubocurarine chloride (Tubocurarini‑chloridum).
This is a curare-like drug with an antidepolarizing effect.
Application: in anesthesiology to relax muscles. Administered intravenously at 0.4–0.5 mg/kg. During surgery, the dose is up to 45 mg.
Side effects: respiratory arrest is possible. To weaken the effect of the drug, prozerin is administered.
Contraindications: myasthenia gravis, pronounced violations kidneys and liver, old age.
Release form: in ampoules of 1.5 ml containing 15 mg of drug No. 25.
Ditilin (Dithylinum), listenone (Lysthenon).
Synthetic short-acting depolarizing muscle relaxants.
Application: tracheal intubation, surgical interventions, reduction of dislocations. It is administered intravenously at the rate of 1–1.7 mg/kg of the patient’s body weight.
Side effects: Possible respiratory depression.
Contraindications: glaucoma. Dithiline solutions cannot be mixed with barbiturates and donor blood.
Release form: ampoules of 5 ml of 2% solution No. 10.
Other drugs are also used in anesthesiological practice: Ardoin ( Arduan), pavulon ( Pavulon), norkuron ( Norcuron), tracrium ( Tracrium), melliktin ( Mellictin). M‑, n‑cholinergic drugs have a blocking effect on m‑ and n‑cholinergic receptors. Among them there are substances that block predominantly peripheral m- and n-cholinergic receptors (peripheral m-, n-cholinergic, or antispasmodics) and have an antispasmodic effect. These are spasmolitin, typhen, etc. There are also drugs that penetrate the blood-brain barrier and block m- and n-cholinergic receptors of the central nervous system, used mainly to treat Parkinson’s disease (cyclodol, dynesin). In addition, there are drugs that have central and peripheral m- and n-anticholinergic effects, for example aprofen.
Spasmolitin (Spasmolythinum).
Peripheral m‑, n‑cholinergic, having an antispasmodic effect.
Application: endarteritis, pylorospasm, spastic colic, peptic ulcer of the stomach and duodenum. Prescribed orally, after meals, 0.05–0.1 2–4 times a day, intramuscularly – 5–10 ml of a 1% solution.
Side effects: dry mouth, headache, dizziness, epigastric pain, local anesthesia.
Contraindications: glaucoma, work requiring quick mental and physical reactions.
Release form: powder.
The main effect of this group pharmacological agents is relaxation of skeletal muscles, that's why they are called muscle relaxants(from three, mys - muscle, and lat. relaxatio - weakening) peripheral type of action. It should be noted that many people have the ability to reduce the tone of skeletal muscles. medicinal substances, affecting the central nervous system(central muscle relaxants), such as tranquilizers.
IN this section Only those drugs that block neuromuscular transmission were considered.
The ancestor of this group of drugs is curare, an arrow poison that the South American Indians used to smear arrowheads. When entering the body of an animal or person when wounded by a poisoned arrow, curare causes paralysis of skeletal muscles. The meat of animals killed by curare is edible because the poison is poorly absorbed in the gastrointestinal tract. Chemical analysis curare showed that its main active principle is an alkaloid d-tubocurarip. contained in plants growing in South America plants of various species of Strychnos, etc.
For a long time, curare was used only in experimental medicine to immobilize animals during experiments. In the clinic medicinal product curare was first used in 1942 to relax muscles during surgery. After this, doctors appreciated the properties of curare and began to use its preparations for surgical operations, with tetanus convulsions and poisoning with convulsive poisons. To date, a number of compounds with curarium-like properties have been synthesized.
At intravenous administration solutions of curare-like agents, relaxation of the neck muscles immediately occurs, then the muscles of the limbs and torso. Lastly, the respiratory muscles relax and breathing stops. If breathing is not supported artificially, then death occurs from asphyxia, therefore, in cases where muscle relaxants are used, breathing is supported by artificial pulmonary ventilation.
According to the mechanism of action of muscle relaxants peripheral action are divided into two groups: anti-depolarizing and depolarizing. The difference between them is that anti-depolarizing muscle relaxants (the main representative of which is tubo-curarine chloride)block n-cholinergic receptors of skeletal muscles. After such a blockade, acetylcholine released from the endings motor nerves, no longer causes depolarization of muscle cell membranes, without which muscle contraction itself is impossible.
It should be noted that the depolarization process is only a starting point complex mechanism muscle contraction, and in order for the muscle to be able to produce repeated contraction, the rapid disappearance of depolarization phenomena and restoration of the original state (repolarization) is necessary. IN normal conditions This alternation of depolarization and repolarization phenomena occurs in neuromuscular synapses due to the release of small “portions” of acetylcholine during the transmission of nerve impulses and the rapid destruction of these same “portions” of acetylcholine by the enzyme ai network l chol and 11 etherase.
By combining with skeletal muscle cholinoreceptors, tubocurarine chloride prevents the effects of acetylcholine on them, g.e. depolarization. However, if the amount of acetylcholine is increased using anticholinesterase drugs, then neuromuscular transmission and muscle contractility are restored. Therefore, anticholinesterase agents (eg, proserine) are tubocurarine antagonists and are used to reverse the effects of curare.
Has a similar mechanism of action diplacin, Anatruxonium, qualidol. Thin to the Cyclops. arduan(nipecurium bromide), pan-curopius(pavulon). All of them are administered intravenously.
Muscle relaxants with a depolarizing effect include ditilin (listenone), which is similar in chemical structure to acetylcholine and, like acetylcholine, causes depolarization of muscle cell membranes and their short-term reduction (fibrillation). However, unlike acetylcholine, dithiline causes a relatively prolonged depolarization (from 3 to 10 minutes), during which the muscles do not respond to the next nerve impulses and relax. As cholinesterase blood ditnlin is destroyed, depolarization gradually fades and muscle contractility is restored. Anticholinesterase substances do not weaken, but, on the contrary, enhance the effect of ditilin and similar drugs, therefore proserin is not used as an antagonist of ditilin. IN Lately Alkaloids have been isolated from some plants (larkspur, etc.) melliktin And Condolphin, which reduce skeletal muscle tone. According to the mechanism of action, these alkaloids are close to tubocurarine, but unlike tubocurarine, they are absorbed from gastrointestinal tract. Millictin and condelfin are prescribed orally to reduce muscle tone in some cases. nervous diseases accompanied by an excessive increase in skeletal muscle tone.
DRUGS -
Tubocurarini chloridum
Administered intravenously at the rate of 0.00025-0.0005 g/kg (0.25-0.5 mg/kg). 11are mainly used by anesthesiologists and surgeons to relax skeletal muscles during surgical operations, when reducing dislocations and repositioning bone fragments in fractures.
Release forms: ampoules of 2 and 5 ml \% solution.
Storage: list A.
Dithylinum
Administered intravenously at the rate of 0.0005-0.0015 g/kg (0.5-1.5 mg/kg). Indications for use are basically the same. as for tubocurarine. Release forms: powder and ampoules of 10 ml of 2% solution.
Storage: list L. Powder - in well-sealed dark glass jars in a cool place protected from light: ampoules - in a place protected from light at a temperature not higher than +5 "C (freezing is not allowed).
Curare-like remedies.
Muscle relaxants - used to relieve muscle tone. For the first time in surgical and anesthesiological practice, muscle relaxants were used by Griffith (American) in 1942, which had great value in the development of surgery: since when using muscle relaxants, the dose of the narcotic substance can be significantly reduced (there is no need to put the patient into the third stage of anesthesia; in order to achieve muscle relaxation, you can operate at stages 1-2, since muscle relaxants will relax the muscles of the abdominal wall). According to the mechanism of action, muscle relaxants are divided into:
1. drugs of a depolarizing type of action (ditilin). The drug excites n-cholinergic receptors and causes depolarization of the postsynaptic membrane, causing short-term muscle spasms. After a short period of time, a myoparalytic effect occurs. The drugs are used to reduce dislocations. In case of overdose, ditilin should not be administered under any circumstances. anticholinesterase drugs(for example, proserine), since ditilin causes depolarization and accumulating acetylcholine causes depolarization and blocking effects occur that are cumulative. In case of an overdose of ditilin, fresh citrated blood containing cholinesterase is injected, which breaks down ditilin. The duration of action of the drug is no more than 15 minutes (which is very convenient to use in anesthesiological practice for intubation).
2. Antidepolarizing drugs - block n-cholinergic receptors, preventing the action of acetylcholine (d-tubocurarine, anatruxonium, etc.) these are curare-like drugs (curare is an Indian poison with which arrows were impregnated). Their duration of action is up to 4 hours. Used in anesthesiological practice in conjunction with anesthesia. After the operation, proserin is administered, which in this case is their antagonist.
CENTRAL N-CHOLINOLYTICS
(pedifen, argenal) have a tranquilizing effect, have good effect for itchy dermatoses).
ATRACURIUM (Atracurium).
Synonyms: Tracrium, Tracrium.
It is a non-depolarizing muscle relaxant. The nature of the action is similar to other drugs in this group. It has a quick, easily reversible muscle-relaxing effect. Has a low ability to cumulate.
After intravenous administration at a dose of 0.5 - 0.6 mg/kg for 90 seconds, intubation is possible. The drug can also be administered as an infusion.
The effect of the drug is removed by the administration of proserin (with atropine) or other anticholinesterase drugs.
Usually, the administration of the drug is well tolerated, changes in of cardio-vascular system not visible. Due to the possibility of histamine release, slight skin hyperemia and, in rare cases, bronchospasm and anaphylactic reactions may be observed.
Contraindications and general precautions are the same as for other non-depolarizing muscle relaxants.
ARDUAN (Arduanum). 2 b, 16 b-bis (4-Dimethyl-1-piperazino)- 3 a, 17 b-diacetoxy-5- a -androstane dibromide.
Synonyms: Pipecurium bromide, Pipecuronium bromide, Pipecuronii bromide, RGH 1106.
Ardouane is a non-depolarizing muscle relaxant. By chemical structure and the action is close to pancuronium (synonyms: Pavulon, Pancuronium, Pancuronii bromidum, Pavulon), which received in last years widely used as a curare-like drug. Both drugs are steroid compounds, but do not have hormonal activity. The curare-like effect is associated with the presence of two quaternary ammonium (onium) groups in these compounds with an optical distance between them approximately equal to the distance between the onium groups in d-tubocurarine.
Under experimental conditions, arduan has a muscle-relaxing effect in doses 2-3 times lower than doses of pancuronium, and acts 2 times longer than pancuronium.
Arduan in usual doses does not cause significant changes in the activity of the cardiovascular system. Only in large doses does it have a weak ganglion-blocking effect; does not cause histamine release.
The muscle relaxant effect of Arduan is removed by proserin.
Ardoin is used for muscle relaxation during surgical interventions different types, including during heart surgery, as well as during obstetric and gynecological operations.
Arduan is administered intravenously.
Ardoin can be used with different types of anesthesia (fluorothane, ether, nitrous oxide, etc.) and must be used during endotracheal intubation of the patient.
Thiobarbiturates (sodium thiopental) prolong muscle relaxation time.
The injection solution is prepared using the supplied solvent immediately before use.
If it is necessary to stop the action of Ardoin, 1 - 3 mg of proserine is administered after preliminary intravenous administration of 0.25 - 0.5 mg of atropine.
The drug is contraindicated in myasthenia gravis and early dates pregnancy. Caution is required when violating excretory function kidneys, since the drug is partially excreted by the kidneys.
DITHILIN (Dithylinum). b-Dimethylaminoethyl succinic acid ester diiodomethylate.
Synonyms: Suxamethonii iodidum, Sukhamethonium iodide.
Similar dichlorides and dibromides are produced under the names: Listenone [Name of the drug (suxamethonium chloride) from Hafslund Nycomed Pharma AG], Miorelaxin, Anectine, Вrevidil M., Celocaine, Celocurin, Сhlorsuccilin, Сuraсholin, Сracit, Сuralest, Diacetylcholine, Lрtosuccin (Yu )), Lysthenon, Myo-Relaxin, Pantolax, Quelicin chloride, Scoline, Succinylcholini chloridum, Sucostrin, Suhamethonii chloridum, Suxinyl, Syncuror, etc.
According to its chemical structure, the dithiline molecule can be considered as a doubled molecule of acetylcholine (diacetylcholine). It is the main representative of depolarizing muscle relaxants. When administered intravenously, it disrupts the conduction of neuromuscular excitation and causes relaxation of skeletal muscles.
Ditylin is destroyed by pseudocholinesterase and breaks down into choline and succinic acid. The drug has a quick and short-term effect; does not have a cumulative effect. For long-term muscle relaxation, repeated administration of the drug is necessary. Fast attack effect and subsequent rapid restoration of muscle tone allow you to create controlled and controlled muscle relaxation.
The main indications for the use of ditilin (listenone) are tracheal intubation, endoscopic procedures(broncho- and esophagoscopy, cystoscopy, etc.), short-term operations (suturing abdominal wall, reduction of dislocations, etc.). With an appropriate dose and repeated administration, ditilin (listenone) can be used for more long operations, however, for long-term muscle relaxation, antidepolarizing muscle relaxants are usually used, which are administered after preliminary tracheal intubation against the background of ditilin. The drug can also be used to relieve seizures due to tetanus.
Ditilin is administered intravenously. Repeated doses of ditilin last longer.
Complications when using ditilin are usually not observed. It should, however, be taken into account that in some cases there may be increased sensitivity to dithiline with prolonged respiratory depression, which may be associated with a genetically determined disorder in the formation of cholinesterase. The reason for the prolonged action of the drug may also be hypokalemia.
Ditylin can be used for various types anesthesia (ether, nitrous oxide, fluorotane, barbiturates). In all cases, the administration of ditilin in large doses is allowed only after the patient is transferred to artificial (controlled) respiration. When using small doses, spontaneous breathing may persist. However, even in these cases it is necessary to have all the devices ready for artificial ventilation lungs.
Prozerin and other anticholinesterase substances are not antagonists with respect to the depolarizing effect of ditilin; on the contrary, by suppressing the activity of cholinesterase, they prolong and enhance its effect.
In case of complications due to the use of ditilin (long-term respiratory depression), resort to artificial respiration, and if necessary, blood is transfused, thus introducing the cholinesterase it contains.
It should be borne in mind that in large doses, ditilin can cause a “double block”, when an antidepolarizing effect develops after a depolarizing effect. Therefore, if after the last injection of ditilin muscle relaxation does not last for a long time (within 25 - 30 minutes) and breathing is not completely restored, resort to intravenous administration of proserin or galantamine (see) after preliminary administration of atropine (0.5 -0.7 ml 0.1% solution).
One of possible complications when using ditilin are muscle pain, occurring 10-12 hours after administration of the drug. The introduction of 3 - 4 mg of d-tubocurarine or 10 - 15 mg of diplacin 1 minute before ditilin almost completely prevents fibrillary twitching and subsequent muscle pain.
Ditilin is contraindicated for children infancy and with glaucoma (a sharp increase in intraocular pressure).
Ditilin should be used with caution when serious illnesses liver, anemia, cachexia, during pregnancy (the drug passes through the placental barrier).
The pharmacological properties of ditilin make it possible to use it in patients with myasthenia gravis.
Do not mix dithiline solutions with barbiturate solutions (a precipitate forms) or with blood (hydrolysis occurs).
2.1 Mechanism of action and main pharmacodynamic effects
Back in the middle of the last century, it was established that the immobility caused by curare depends on the cessation of the transmission of excitation from the motor nerves to the muscles (Claude Bernard, E.V. Pelikan). Currently, this effect of curare is considered to be the result of blocking n-cholinergic receptors in skeletal muscles. This deprives them of the opportunity to interact with acetylcholine, which is a neurotransmitter of nervous excitation formed in the endings of motor nerves. Synthetic compounds, alkaloids and their derivatives are also used as muscle relaxants.
Different muscle relaxants have different mechanisms of action, and due to the peculiarities of their influence on the process of synaptic transmission, they are divided into two main groups.
A. Non-depolarizing (antidepolarizing) muscle relaxants (pachycurare).
These include d-tubocurarine, diplacin, qualidil, anatruxonium and other drugs that are acetylcholine antagonists. They paralyze neuromuscular transmission due to the fact that they reduce the sensitivity of n-cholinergic receptors of the synaptic region to acetylcholine and thereby eliminate the possibility of depolarization of the end plate and excitation of the muscle fiber. Compounds of this group are true curare-like substances.
The pharmacological antagonists of these compounds are anticholinesterase substances: by inhibiting the activity of cholinesterase in appropriate doses, they lead to the accumulation of acetylcholine in the area of synapses, which, with increasing concentration, weakens the interaction of curare-like substances with n-cholinergic receptors and restores neuromuscular conduction.
B. Depolarizing drugs (leptocurare) cause muscle relaxation, providing a cholinomimetic effect, accompanied by persistent depolarization, that is, acting in a similar way to how excess amounts of acetylcholine act, which also disrupts the conduction of excitation from the nerve to the muscle. Drugs in this group are hydrolyzed relatively quickly by cholinesterase and have a short-term effect when administered once. A representative of this group is ditilin. Some muscle relaxants may have mixed antidepolarizing and depolarizing effects.
2.2 Indications for the use of curare-like drugs
Diplacin, tubocurarine and other antidepolarizing muscle relaxants are used mainly in anesthesiology as a muscle relaxant, causing long-term muscle relaxation during surgery and stopping voluntary breathing.
Sometimes used in orthopedics tubocurarine to relax muscles during reposition of fragments, reduction of complex dislocations, etc. In psychiatric practice, tubocurarine is sometimes used to prevent traumatic injuries in convulsive therapy of schizophrenia. Diplacin can be used to reduce or relieve seizures during complex therapy tetanus.
Melliktin, unlike other antidepolarizing muscle relaxants, it has a blocking effect on neuromuscular conduction when taken orally. In this regard, the drug is used to reduce muscle tone when pyramidal insufficiency vascular and inflammatory origin, postencephalitic parkinsonism and Parkinson's disease, Little's disease, arachnoencephalitis and spinal arachnoiditis, as well as other diseases of a pyramidal and extrapyramidal nature, accompanied by increased muscle tone and motor function disorders.
Ditilin, which is a depolarizing muscle relaxant, when administered, allows you to create controlled and controlled muscle relaxation. Due to its properties, the main indications for the use of this drug are tracheal intubation, endoscopic procedures (bronchoscopy, esophagoscopy, cystoscopy), short-term operations (suturing the abdominal wall, reducing bone fragments and dislocations, etc.). With an appropriate dose and repeated administration, ditilin can be used for longer operations, however, for long-term muscle relaxation, antidepolarizing muscle relaxants are usually used, which are administered after preliminary tracheal intubation against the background of ditilin. In addition, the drug can also be used to eliminate seizures due to tetanus.
2.3 Pharmacokinetics and dosage regimen of drugs
By chemical structure d-Tubocurarine, diplacin, ditilin and others are quaternary ammonium compounds ; They are characterized by the presence of two onium groups. In the process of searching for curare-like substances, it was found that curare-like activity may also have tertiary amines. From plants different types Larkspur (Delphinium), fam. buttercups (Ranunculaceae) alkaloids are isolated ( condelfin, methyllycaconitine etc.), which are tertiary bases , but with pronounced curare-like properties.
The main representative of the group non-depolarizing muscle relaxants is tubocurarine chloride (Tubocurarini chloridum) . Available in ampoules of 1.5 ml of 1% solution for intravenous administration, it belongs to list A. The effect of the drug develops gradually; Usually muscle relaxation begins after 1 - 1½ minutes, and the maximum effect occurs after 3 - 4 minutes. Doses of tubocurarine, as well as other muscle relaxants, depend on the anesthesia used. When using nitrous oxide, intravenous administration at a dose of 0.4 - 0.5 mg/kg causes complete muscle relaxation and apnea lasting 20 - 25 minutes. Satisfactory muscle relaxation abdominals and limbs continues for 20 - 30 minutes after the appearance of spontaneous breathing. If a longer effect is required, tubocurarine is administered repeatedly, and due to the ability to cumulate, each subsequent dose should be 1/2 - 2 times less than the previous one. Typically, for an operation lasting 2 - 2½ hours, 40 - 45 mg of the drug is consumed. For ether anesthesia, the initial dose of tubocurarine is 0.25 - 0.4 mg/kg.
Diplacinum - an antidepolarizing muscle relaxant, similar in its mechanism of action to tubocurarine. It belongs to list A and is available in ampoules of 5 ml of 2% solution, which is administered intravenously. When administered at a dose of 1.5 - 2 mg/kg, it relaxes the muscles of the limbs and abdominals without stopping spontaneous breathing. At a dose of 4 - 5 mg/kg, it causes complete muscle relaxation and apnea lasting 20 - 30 minutes in 4 - 5 minutes. After spontaneous breathing is restored, relaxation of the abdominal muscles and limbs continues for some time. If it is necessary to prolong the effect, diplacin is reintroduced, reducing the dose to? - ½ original. In total, during an operation lasting 1½ - 2 hours, 400 - 700 mg of the drug is consumed (20 - 35 ml of a 2% solution). During ether and fluorotane anesthesia, the dose of diplacin can be increased.
Qualidil (Qualidilum) belongs to list A and is available in ampoules of 1; 2 and 5 ml of 2% solution. The drug is administered intravenously. At a dose of 1 mg/kg, the drug causes muscle relaxation, lasting about 10 minutes, with some respiratory depression. Doses of 1.2 - 1.5 mg/kg cause muscle relaxation lasting 15 - 20 minutes, while in some patients apnea occurs for 4 - 5 minutes. Typically this dose is used in cases where tracheal intubation is performed using dithiline. Complete muscle relaxation occurs at doses of 1.8 - 2 mg/kg; apnea lasts an average of 17 - 25 minutes. At a dose of 2 mg/kg, muscles begin to relax after 1½ - 2 minutes, and apnea and complete muscle relaxation occur after 2½ - 4 minutes. The exit from the state of curarization occurs gradually: after the appearance of independent breathing, muscle relaxation persists for 15 - 20 minutes; After 25-30 minutes, muscle tone and breathing are usually completely restored. If it is necessary to lengthen the effect of qualidil, it is reintroduced, reducing subsequent doses by 1/2 - 2 times. In total, 20 - 220 mg of the drug is consumed for an operation lasting 1½ - 2 hours.
Melliktinum according to its chemical structure, it belongs to tertiary bases, is available in tablets of 0.02 g (20 mg) and belongs to list A. This is one of the few curare-like drugs prescribed orally. Take it 0.02 g starting from 1 time and up to 5 times a day. The course of treatment is from 3 weeks to 2 months. After a 3-4 month break, the course of treatment is repeated.
As already noted to depolarizing muscle relaxants applies Dithylinum The drug belongs to list A and is available in the form of a 2% solution in ampoules of 5 or 10 ml. Similar dichlorides and dibromides are available under the names: Listenon, Myo-relaxin, Brevidil M, Succinal, etc. . According to its chemical structure, dithiline can be considered a double acetylcholine molecule (diacetylcholine). It is the main representative of depolarizing muscle relaxants. When administered intravenously, it disrupts the conduction of neuromuscular excitation and causes relaxation of skeletal muscles. The drug has a quick and short-term effect; does not have a cumulative effect. For long-term muscle relaxation, repeated administration of the drug is necessary. The rapid onset of the effect and the subsequent rapid restoration of muscle tone allow you to create controlled and controlled muscle relaxation. Ditilin is given intravenously. For intubation and for complete relaxation of skeletal and respiratory muscles during surgery, the drug is administered at a dose of 1.5 - 2 mg/kg. For long-term muscle relaxation during the entire operation, the drug can be administered fractionally every 5-7 minutes at 0.5-1 μ/kg. Repeated doses of ditilin last longer.
2.4 Contraindications and side effects
An absolute contraindication for the use of muscle relaxants is myasthenia gravis. The exception is ditilin, pharmacological properties which allows its use in such patients.
The use of ditilin is contraindicated in infants and glaucoma(a sharp increase in intraocular pressure is possible).
Almost all drugs in this group should be used with caution when liver and kidney diseases, cachexia, pregnancy(drugs penetrate the placental barrier), as well as in the elderly and old age . Some drugs (qualidil, melliktin, anatruxonium) should be used with caution in patients with cardiovascular disorders.
It must be remembered that the use of muscle relaxants is permissible only if there are conditions for tracheal intubation and artificial ventilation of the lungs. When ditilin is used in small doses, spontaneous breathing can usually be maintained, however, even in these cases it is necessary to have all the devices for artificial respiration ready. In addition, it should be taken into account that in some cases there may be increased sensitivity to dithiline with prolonged respiratory depression, which may be associated with a genetically determined disorder in the formation of cholinesterase. Hypokalemia may also be a reason for prolonged action of the drug.
Antagonists anti-depolarizing muscle relaxants are proserin and galantamine, which are administered together with atropine. For complications associated with hypersensitivity to the drug or an overdose of the drug, oxygen should be prescribed and 0.5 - 1 ml of a 0.05% solution of proserine together with atropine (0.5 - 1 ml of a 0.1% solution) should be slowly injected into a vein. With regard to the depolarizing effect of ditilin, prozerin and other anticholinesterase drugs are not antagonists, but on the contrary, by suppressing the activity of cholinesterase, they prolong and enhance its effect. In this regard, in case of complications with the administration of ditilin (long-term respiratory depression), artificial respiration is resorted to, and, if necessary, blood is transfused, thus introducing the cholinesterase contained in it. In addition, a peculiarity is that in large doses, ditilin can cause a “double block” when, after a depolarizing effect, an antidepolarizing effect develops. Therefore, if after the last injection of ditilin muscle relaxation does not go away for a long time (within 25 - 30 minutes) and breathing is not completely restored, they resort to the administration of proserin along with the preliminary administration of atropine (see above).
Thus, curare-like drugs belong to the group potent substances and have strictly limited use in anesthesiological practice.
Curare-like drugs are used during surgical operations to relax skeletal muscles.
Curare, a specially processed juice of a South American plant, has long been used by Indians as an arrow poison that immobilizes animals. In the middle of the last century, it was established that the relaxation of skeletal muscles caused by curare is realized by stopping the transmission of excitation from motor nerves to skeletal muscles.
Basics active substance curare is an alkaloid d-tubocurarine. Currently, many other curare-like drugs are known. The mechanism of action of these drugs is the formation of a complex with the H-cholinergic receptor site of the muscle fiber membrane (postsynaptic membrane). Depending on the functional properties of the resulting complex, muscle relaxants are divided into groups:
1) means of anti-depolarizing (non-depolarizing) action;
2) means of depolarizing action.
Depolarizing muscle relaxant suxamethonium chloride (ditilin) is widely used in medical practice. Unlike acetylcholine, which is instantly destroyed by cholinesterase, dithiline produces persistent depolarization: after a short (several seconds) contraction, muscle fiber relaxes, and its N-cholinergic receptors lose sensitivity to the mediator. The effect of ditilin ends after 5-10 minutes, during which it is washed out of the synapse and hydrolyzed by pseudocholinesterase.
Naturally, anticholinesterase drugs, promoting the accumulation of acetylcholine, prolong and enhance the effect of depolarizing muscle relaxants.
Ditilin is used for short-term muscle relaxation during tracheal intubation, reduction of dislocations, reposition of bones in fractures, bronchoscopy, etc. Complications:
1) muscle postoperative pain. At the beginning of depolarization, muscle fibrillar contractions and twitching appear; they are the cause of postoperative muscle pain;
2) increased intraocular pressure;
3) disturbance of the rhythm of cardiac activity. In case of an overdose of ditilin, fresh blood (high pseudocholinesterase activity) is transfused and electrolyte disturbances are corrected. The use of muscle relaxants is permissible only if there are conditions for tracheal intubation and artificial ventilation.
Loading...