Miorolaxants like poison Kurare. Runtime funds (Miorlaxants peripheral action)
Runtime funds
Runtime funds (miorolaxanta Peripheral action) block n-cholinoreceptors of skeletal muscles and cause relaxation of skeletal muscles.
Classification
By mechanism of action They can be divided into substances:
1) antide-polarizing (competitive) type of action that block the H-cholinoreceptors of skeletal muscles prevent the interaction of n-cholinoreceptors with acetylcholine and the offensive of the muscular plate depolarization, followed by its depolarization (tubocurarine, diplocine, melkin, etc.);
2) depolarizing Type of action that cause a resistant depolarization of the muscular plate that prevents depolarization offensive (dithiline et al.);
3) mixed type Actions giving antidehaloorizing and depolarizing effects (dioxonium, etc.). Miorlaxants cause muscle relaxation in a certain sequence: the facial muscles, the muscles of the limbs, voice ligaments, torso, diaphragms and intercostal muscles.
By duration of action Miorosanta can be divided into three groups:
1) short action (5-10 minutes) - ditilin;
2) medium duration (20-40 minutes) - Tubokurarin-chloride, diplocin, etc.;
3) long action (60 minutes or more) - Anatruksonius.
In addition to the listed stripping funds in anesthesiology, Arduan, Pavlon, Norkuron, Trespan, Mellctin are used.
Brief description of the pharmacological group. The stripping means blocked H-cholinoreceptors of skeletal muscles and cause relaxation of skeletal muscles.
In our period of the rapid development of large surgery, anesthesiology, which is now largely based on muscle relaxants, which selectively affecting neuromuscular synapses, paralyzing them, are perfectly relaxing arbitrary muscles. These minelaxants were also called rapid preparations. Kurar, South American poison, extracted from Lian (Liana Chondroudenaro Tomcntosum), from the bark and the roots of Strichuos Toxifera, etc., growing in South America, especially in British Guiana. The word "Coarara" comes from the name of the river in Guiana - Kuravar or killing birds, where these plants grow. From time immemorial, the Indians with this poison poison the arrows, going to hunt, or using them in intergovernmental battles or in battle with Europeans - colonizers.
The first information about the coarara became known in Europe shortly after the opening of the Columbus of America.
Spaniards - a historian of the bed (1510-1560) and the monardess doctor (1493-1588) described by Kurar.
In 1595, he said about the same, and the first experimental work on currency with the use of antidotes of sugar and cooking salts belongs to the Frenchman Kondimenna (1745). He was confident that Kurara is contained in 30 types of plants. The Italian Fontana in 1781 established that the berare does not paralyze nerves, and destroys the excitability of the transverse muscles. In 1811, British British noted that Kurara stops his breath, it does not directly act on the heart and that an animal life can be saved with an artificial respiration. Apparently the authors of the film, which you watched, meant Brodie on the example of the revival of the donkey with an artificial respiration after the curarm poisoning.
It is known that the transfer of momentum from the nerve to the muscle is carried out using acetylcholine mediator, which is formed in the nervous end in synapse. Acetylcholine acts on the recipe substance of the myoneurological compound and thereby causes the contraction of the muscles, but it is destroyed after 1/1000 seconds. Holinesterase. Along the minor compound or postsynaptic membrane is in a state of polarization, when the inner surface of Brodi is on an example of an oxv with an artificial respiration after curarm poisoning.
French doctors of the Rule and Boussingo in 1928 allocated the active start of Kurara and called him Kurarin. Experiments with Kurare produced Claude Bernard (1844-1851), Russian scientists Pelican (1857) and Dybkovsky (1861). In convulsions, for the first time with the medical goal, Kurara was used in 1850 the Italian velli. In 1878, Gunter used Kurar at a tetanus and rabies. At the same time, Popov, Corinora, and in the consequence of the Bremer (1927), the grinding and Vesta Kurar were successfully used in tetanus, rabies, epilepsy and roaster. Sporadic cases in experiments and clinics belong to Pavlov, Kravkov, Vvedensky, Karasik and Anichkovo.
For the first time, pure pipe courier from Kurara was obtained by King in 1935, and three years later, Mc Incer and the Dutcher received intocostrin, and in the clinic it was used in 1940-41. Bennet and his staff at mental diseases To prevent convulsion with electrostrophopic therapy. A major Canadian anesthesiologist Griffith and his disciple Johnson in 1942 with surgery to relax muscles for the first time in the history of surgery applied to intocostrine. Currently, both of us and abroad have been synthesized many Miorosanta.
What is the mechanism of action of these drugs? Bernard (1851) and Pelican (1857) was installed (1857), Miorosanta blocked the transfer of the nerve shear impulse to the muscle. In 1958-59 WASSER with the help of labeled tubar and decamenia atoms determined that relaxants in the body are fixed mainly in the region of end plates of myioneral synapses.
It is known that the transfer of momentum from the nerve to the muscle is carried out using acetylcholine mediator, which is formed in the nervous end in synapse. Acetylcholine acts on the recipe substance of the myoneurological compound and thereby causes the contraction of the muscles, but it is destroyed after 1/1000 seconds. Holinesterase. Along the minor compound or postsynaptic membrane is in a state of polarization, when electrothative potassium electrostatic ions are located on its inner surface, and sodium electropositive ions on the outer surface.
Acetylcholine causes depolarization, i.e. Moves sodium ions to the inner, and potassium ions - to the outer surface of the membrane, thereby the impulse passes through the synaps and the muscle is reduced. Depending on the mechanism of action, the strip-like substances are divided into depolarizing (like acetylcholine) and non-polarizing muscle relaxants.
The first group of drugs acts like acetylcholine, causes depolarization, but a longer, muscles convulsively decrease, starting from head and ending with a diaphragm. Soon these relaxants are destroyed by pseudocholinesterase, and repolarization occurs, that is, the muscles relaxes. Non-opalarizing relaxants block the receptors of the myoneral compound, the action of acetylcholine does not appear, i.e. The depolarization does not occur, and the muscles are relaxed, breathing stops. However, when using the antidote of prozerne, which oppresses the cholinexterase, it can create conditions for accumulation of acetylcholine, which breaks through the blockade and restores its action, i.e. The muscles are re-reduced again, spontaneous breathing begins.
Ditilin, Decayatonium-iodine, Miorolaxin, Curacite, Leafenon, Miorolaxin, Skolin, Succinylcholine, Succikuran, Succietonium Bromide, Succicoran, Succimium Bromide, Succicoran, Succietonium Bromide, Succitonium-Bromide, Succitonium-Iodide, Succitonium-iodide, etc.
The nonpolarizing relaxants include: drugs from a natural true coarara - D-tubularian, Meekosostrins, Metubin and Betta Erythrosidin, as well as synthetic - diplocin, pyrolaxan (abroad analogues of Flyxedil and Gallemin), Paramyon, Milaksen, Laudolyizin, etc. You need clearly Submit dosage, duration of action and complications when using these relaxants. In more detail, physico-chemical and pharmacodynamic properties will analyze practical activities. These properties are widely used in surgery in order to reduce harmful influence Basic narcotic drug (With a minimum dose of drugs, complete relaxation occurs), conducting controlled respiration with reinforced oxygen supply (when there is a risk of bilateral pneumothorax), for removing seizures with gliotermia, tetanus rabies, before intubation, with endoscopy, fracture and dislocation.
Mioryelaxants do not cause sleep, anesthesia, so before you need to turn off consciousness. The bulk of them does not have a harmful effect on the heart, the liver, kidneys, they quickly destroy, are outlined from the body, so it is important that these organs are healthy.
It should also be remembered that some of them are capable of cumulating, so under overdose and when re-administration They can stop breathing a few hours after the restoration of spontaneous breathing, i.e. Recovernment comes. For the prevention of this complication, it is recommended to introduce prozer-antidote prozer-antidote at the end of the operation. The patient during the day since the introduction of the drug should be under observation.
In general, when using muscle relaxants, the respiratory stop is potentially possible, so you always need to be prepared for intubation and methods of artificial respiration.
The following groups of artificial respiratory methods are distinguished:
a) manual (Sylvester, Shyler, Labard)
b) hardware (semi-automatic, and automatic.)
c) system of lungs in the lungs - 1) from mouth to mouth, 2) from the mouth to
To tell you!
Kurarine is a modular poison, poorly absorbed from the gastrointestinal tract into the blood, and in the gastrointestinal tract. The action is manifested only when hitting blood, bypassing the gastrointestinal tract. At the same time acts only on the H-XP skeletal muscles, causing full or partial relaxation of skeletal muscles. Due to the main action on skeletal muscles received the second name miorosanta.
Found the main use in surgical practice to relax skeletal muscles during operations on the bodies of the chest and abdominal cavity. In addition, muscle relaxants can be used for convulsive therapy and for the treatment of spastic paralysis. High doses of muscle relaxants can cause the oppression of the respiratory center, and in particularly severe cases - the palsy of the respiratory center and death.
Functional antagonists of strip-like funds are AHE: Prezero, Fizostigmin.
Tubokuran,Tubocurarini.chloridum, list "A"
Salt alkaloid tubocuarine, in therapeutic doses blocks H - XP skeletal muscles without a significant change in the basic functions of the body. In large quantities, the H - XP of the adrenal glands and the sylocarotide zone can be blocked, which can lead to a decrease in blood pressure and inhibition of breathing. In addition, large doses of this substance can contribute to the exhaustion of the organism cells of the Histamine poison, which becomes active and can cause a spasm of bronchi.
It is applied only in hospital conditions during surgical operations.
FV - ampoules 2 and 5 ml. 1% solution.
Ditylin,Dithylinum, List "A", "Miorolaksin"
The activity is significantly inferior to tub-cancer, the action is developing with intravenous introduction after 30 seconds and lasts 3 to 7 minutes.
It is used during anesthesia for short-term relaxation of skeletal muscles, and in the overdose of this preparation, AHE does not apply, because They strengthen dithiline toxicity.
FV - AMP. 5 and 10 ml of 2% solution.
Substances with a predominant action on ar (adrenergic agents)
These are funds affecting sympathetic adrenergic innervation .
As a mediator in adrenergic synapses, norepinephrine is the most important, which excites the AR cell membranes. Norainerenalin synthesis occurs in the endings (axons) of sympathetic nerves (i.e., in postganglyonary SNS fibers). The initial substance for the synthesis of norepinephrine is the amino acid of tyrosine, which under the influence of certain enzymes undergo a number of changes: tyrosine - dioxiphenylalanine (dof) - dioxiphenylalaninamin (dofamine) - norepinephrine. This complex biochemical process occurs in adrenergic nerves, and the resulting norepinephrine deposited in the nerve endings in special entities - vesicles. During the intake of the nervous impulse, part of the norepinephrine is thrown into the synaptic slit and excites the AR. The effect of the norepinephrine mediator briefly, because Most of it (80%) after the transfer of the pulse is subjected to reverse capture by nerve endings. The part of the mediator is inactivated by special enzymes: monoamine oxidase (MAO) and catecholorthylTransferase (CT).
The α-and β-adrenoreceptors are distinguished, which is due to their different sensitivity to norepinephrine, adrenaline and a number of pharmacological substances. Quantitative ratio in organs α - and β - ar is different.
α - ar is located mainly in the vessels of the skin, mucous membranes, kidneys, in the organs of the abdominal cavity, in the lungs and muscles, in the radar muscle of the eye.
β -ar are divided by β 1 - and β 2 - ar. Mostly β 1 -ar are located in coronary vessels and conductive heart system, β 2 - in bronchi, vessels of skeletal muscles and the uterus.
Pharmacological exposure mechanismsadrenergic synapses are quite diverse. Some LV interact with the AR postsynaptic membranes, causing their excitation or oppression and corresponding changes in metabolism and cell function. The effect of other drugs is directed at the end of the sympathetic nerves and and the presynaptic membranes. At the same time, the drug may disrupt the synthesis of norepinephrine, its deposit in vesicles, isolation into the synaptic gap, reverse grip Mediator with the presynaptic endings of the nerves. Some substances oppress the processes of enzymatic inactivation of norepinephrine. The combinations of various mechanisms of action in one drug substance are possible.
Classification of adrenergic agents.
Adrenomimetics - exciting AR.
Adrenoblays - blocking AR.
Sympathomimetics (adrenomimetics indirect action) - do not affect directly on ar, but contribute to the release of norepinephrine from the presynaptic endings and therefore enhance adrenergic reactions.
Sympatholites - block sympathetic innervation at the level of ending postganglyonary sympathetic nerves.
Adrenomimetics
α - β- am direct action
A typical representative of this group
ADRENALIN- It is formed from norepinephrine in adrenal brainstab cells, according to its action and origin is steroid hormone. It is a direct stimulating effect on α, β 1, β 2 - AR. In medical practice is used as
hydrochloride adrenaline solution,Solutio.Adrenalini.hydrochloridum, List "B", 1ml.
The action on the organs is expressed by the following pharmacological effects (as in the excitation of the SNA, except P.7):.
1. Expansion of coronary vessels, skeletal vessels, brain and lungs. Under the conditions of a whole body, the vasoconductive effect of adrenaline prevails, which leads to an increase in blood pressure.
2. Strengthening the work of the heart and the increase in cardiac rhythm.
3. The narrowing of the vessels of the abdominal organs, skin and mucous membranes.
4. Relaxing the muscles of the bronchi, intestines.
5. Expanding the pupil as a result of a reduction in the radial muscle of the eye.
6. Reducing the uterus, spleen.
7. Improving the tone of the Sphinters of the tract and bladder.
8. Increasing the amount of blood sugar as a result of amplification of metabolism and gluconeogenesis stimulation.
9. Improving the operability of skeletal muscles due to an increase in glucose and improving the blood supply to skeletal muscles.
10. Improving the secretion of adrenocorticotropic hormone (ACTH).
11. Increasing the number of free fatty acids in the blood due to the stimulation of lipolysis.
12. Small excitement of the central nervous system (anxiety, tremor, etc.)
Used:
how vasoconstrictor With shock, collapse, acute hypotension. For intravenous administration 5 minutes acts at subcutaneous - 30 minutes.
With anaphylactic shock and some allergic ruggings of immediate type.
Under acute heart weakness, when the heart is stopped (in this case, adrenaline is introduced intracardiac).
To relieve attacks of suffocation at bronchial asthma (BA).
Together with local anesthetics for the narrowing of vessels, delays in the suction of anesthetics and the extension of their action.
In case of insulin overdose or under the hypoglycemic coma to restore the amount of sugar in the blood.
Externally in the eye practice, ENT practice for narrowing vessels.
Contraindications for use.
Hypertonic disease.
Atherosclerosis.
Diabetes.
Thyrotoxicosis (increase in metabolism).
Pregnancy.
With fluorotan, cyclopropane and chloroform anesthesia (arrhythmias, extrasystoles may occur).
Appointed: intravenously, subcutaneously, intramuscularly, intracardiac, externally. Inside is not prescribed, because collapsed in the gastrointestinal tract.
FV - in ampoules 1 ml of 0.1% solution, is obtained by synthetic, or isolated from adrenal cattle.
NoradrenalinNoradrenalini.hydrotartras., List "B"
Unlike adrenaline excites mainly α -Ar, slightly - β 1 - AR, therefore exhibits a stronger vasoconstrictor action. Practically does not act on bronchi, does not show hyperglycemic effect, regenerates heart rate rhythm. It is used as a vesseloring agent at shock, collapse, acute hypotension (as a result of injuries, surgical interventions). Only intravenously is introduced; Better - through the catheter, because Causes tissue necrosis due to the strong spasm of the vessels. Other injection paths are not used.
Contraindications.
Atherosclerosis.
Hypertension.
FV - in ampoules 1 ml. 0.1% - 0.2% solution.
1) means of nonpolarizing action;
2) means of depolarizing action.
Coarara, specially processed juice of the South American Plant, for a long time, was used by the Indians as a fitting poison, immobilizing animals. In the middle of the last century, it was established that the relaxation of the skeletal muscles caused by the coarara is implemented due to the cessation of excitation transmission from the motor nerves on skeletal muscles.
Basic Active Substance Kurare - Alkaloid d-tubocurarine. Currently, there are also many other strip-like drugs.
Indications for the use of all muscle relaxants:
Curampotic drugs are used at surgical operations For relaxation of skeletal muscles.
For IVL during operation
Removing dislocation, reposition of bone fragments
Causes
Nonpolarizing Miorosanta.
Tubocuarine Chloride, Pipecuronia Bromide, punchonia Bromide. These drugs during intravenous administration cause rapid relaxation of skeletal muscles, which continued 30-60 minutes. First, the muscles of the head and neck are relaxed, then the limbs, voice ligaments, torso, and, at the last stage (at large doses), respiratory (intercostal and diaphragm muscles), which leads to a stop of breathing. On Central nervous system They do not act, as the blood hematoretical barrier is bad.
Mechanism of action
Antide-polarizing muscle relaxants, binding to the H-cholinoreceptor, cover it (shielded) from the effects of synaptic acetylcholine. As a result, the nerve impulse will not cause depolarization of the muscular fiber membrane (therefore drugs are called non-compolant).
These compounds compete (competitive muscle relaxants) with acetylcholine for H-cholinoreceptors of the postsynaptic membrane: with an increase in the amount of acetylcholine in synapse (for example, with the introduction of anticholinesterase drugs), the mediator displaces the muscle relaxant from the membrane and forms a complex with a receptor, causing depolarization.
Antagonists Antide -olarizing (competitive) minelaxants are anticholinesterase agents (prozerne et al.), which, inhibiting synaptic cholinesterase (an enzyme that destroys acetylcholine), contribute to the accumulation of acetylcholine. They are used in the overdose of nonpolarizing muscle relaxants.
Indications for use
With large operational interventions For long-term muscle relaxation.
In addition, they are used to relieve seizures in patients with severe tetanus form.
Non-opalarizing drugs can cause by-effect - reduction of blood pressure, blocking H-cholinoreceptors of ganglia.
Depolarizing Miorosant
suksmethonia chloride, iodide (dintin) It is widely used in medical practice.
Mechanism of action
By virtue of large structural similarities with acetylcholine, it not only binds the H-cholinoreceptor of skeletal muscles (by analogy with a tubocrarian), but also excites it, causing depolarization of the postsynaptic membrane (like acetylcholine). Unlike acetylcholine, instantly destroyed by cholinesterase, dichiline gives a resistant depolarization: after a short (a few seconds) reduction, muscle fiber relaxes, and its H-cholinoreceptors lose sensitivity to the mediator. Dithiline's action ends after 5-10 minutes, during which it is washed out of synapse and hydrolyzed pseudocholinesterase.
Naturally, anticholinesterase agents, contributing to the accumulation of acetylcholine, lengthen and enhance the action of depolarizing muscle relaxants.
Applied Ditylin for short-term minelaxation in the intubation of the trachea, the return of dislocations, the repositions of bones during fractures, carrying the bronchoscopy, etc.
1) Muscular postoperative pain. At the beginning of depolarization, muscle fibrillar cuts appear, twitching, they are the cause of postoperative muscle pain;
2) an increase in intraocular pressure;
3) violation of the rhythm of cardiac activity. When dithiline overdose is overflowing fresh (high pseudocholineserase) blood and corrected electrolyte disorders. The use of muscle relaxants is permissible only if there are conditions for the intubation of the trachea and artificial ventilation of the lungs.
Atropine Solutio ATROPINI Sulfatis 1% for in / c, in / m or p / k admin, pills, eye drops (1%)
Application: - intestinal spasms and bile and urinary tract, pylorospasm, bradyarithmia, for premedication, poisoning with phosphorreering agents, x-ray studies Gastroy
Eye DNA Study (rarely), to create functional rest inflammatory diseases And eye injuries, ulcerative disease Stomach I. duodenal gut, bronchial asthma, Bronchitis with mucus hyperproduction.
Side effects: MIDRIAZ, accommodation paralysis, tachycardia, intestinal atony and bladder, headache, dizziness, loss of touch.
The main effect of the strip-like drugs is to relax a skeletal muscles, so they are called minelaxants peripheral action. The twin priest of this group of pharmaceuticals is curare - deadly poison made of plant bark Strychnos Toxifera.With which the aborigines of South America, for a long time, lubricated the arms for immobilization of animals.
Chemical analysis of Kurare showed that its main active substance is alkaloid d-Tubokuran. Currently, there are many other strip-like drugs in medicine.
The mechanism of action of stripping funds
The mechanism of action of stripping means is to form a complex with a H-cholinoreceptor area of \u200b\u200bthe muscle fiber membrane (postsynaptic membrane). The strip-like tools are used to relax skeletal muscles when conducting surgical interventions; Usually administered intravenously.
By mechanism of action runtime funds are divided into the following three groups:
- antide -olarizing (non-polarizing, competitive) drugs - tubocurarine, mellortion, etc.;
- depolarizing drugs - suucametonium (suucamenia chloride, suucamenia iodide, etc.);
- preparations of mixed type of action (dioxonium).
The mechanism of action of antidehaloorizing drugs is the blockade of n-cholinoreceptors of end plates of skeletal muscles, which, according to the principle of competitive antagonism, prevents the depolarizing influence of acetylcholine ⮕ impairment of neuromuscular transmission ⮕ relaxation of skeletal muscles.
The mechanism of action of depolarizing muscle relaxants, by contrast, is due to the excitation under the influence of the drugs of n-cholinoreceptors of end plates of skeletal muscles, followed by a resistant depolarization of the postsynaptic membrane and relaxation of skeletal muscles. At the same time, the neuromuscular transmission first is briefly facilitated, which is accompanied by muscle twitching - firecakes. After a short period of time, the myoparalytic effect comes.
Miorolaxants with a mixed mechanism of action first cause short-term depolarization of the end plate of the skeletal muscle, which is replaced by the non-polarizing unit.
Strip-like medicinal products relax the satellites in a certain sequence. Initially, the muscles of the face, the muscles of the neck, then the muscles of the limbs and the body and, finally, respiratory muscles are relaxed. Paralysis diaphragm is accompanied by stopping breathing.
Overdose of stripped means
The range between doses in which the stripped preparations are paralyzed by the most sensitive muscles, and the doses necessary for the complete respiratory stop, is called a latitude of myoparalytic action.
Assistance in overdosing the muscle relaxants of the antide -olarizing and depolarizing type of action is fundamentally different. For antide -olarizing (competitive) funds with active antagonists are anticholinesterase agents, the introduction of which restores neuromuscular transmission. On the contrary, with the poisoning of suucameton, anticholinesterase agents are contraindicated, since it is aggravated by the effect of this depolarizing Miorosanta. This is explained by the peculiarities of the chemical structure of suxametonia, which is two adhesive acetylcholine molecules.
On the one hand, due to the chemical similarity with acetylcholine, Suksametonius causes a resistant depolarization of muscle fiber, leading to its subsequent relaxation. On the other hand, the use in these conditions of anticholinesterase drugs aggravates the depolarization of skeletal muscles and will prolong the miorexing effect of suxametonia.
This occurs as a result of accumulation in the synaptic slit even more acetylcholine. Being an analogue of acetylcholine, suucametonius in the end for 5-10 minutes is destroyed by the enzyme acetylcholinesterase, after which neuromuscular transmission and breathing are spontaneously restored. Therefore, in the absence of cases of poisoning by Sucmametonius to restore respiration, it suffices to use artificial ventilation of light (IVL).
It should be borne in mind that persons with the genetically determined deficiency of acetylcholinesterase apnea (respiratory stop) can be maintained up to 6-8 hours. In this case, the poisoning of suucamene is eliminated by the introduction of fresh citrate blood containing plasma acetylcholineserase.
In view of some gangli-blocking activity, antide-polarizing Miorolaxans can reduce arterial pressure And provoke tachycardia. Application Subsamethonia may be accompanied by muscular pain and the heart arrhythmias due to increasing the concentration of potassium ions in extracellular fluid.
Sources:
1. Lectures on pharmacology for higher medical and pharmaceutical education / V.M. Blyukhanov, Ya.F. Zverev, V.V. Lampatov, A.Yu. Jarikov, O.S. Talalaeva - Barnaul: Publishing House, 2014.
2. Pharmacology with recipe / Gaevy MD, Petrov V.I., Gaeva L.M., Davydov V.S., - M.: ICC Mart, 2007.