Curarin is a shot poison, it is poorly absorbed from the digestive tract into the blood, and is destroyed in the digestive tract. The action is manifested only when it enters the bloodstream, bypassing the gastrointestinal tract. In this case, it acts only on the H-HR of skeletal muscles, causing complete or partial relaxation of the skeletal muscles. In connection with the main effect on skeletal muscles, they received a second name muscle relaxants.
Found the main application in surgical practice for relaxation of skeletal muscles during operations on the organs of the thoracic and abdominal cavity... In addition, muscle relaxants can be used in seizure therapy and for the treatment of spastic paralysis. High doses of muscle relaxants can cause depression of the respiratory center, and in severe cases, paralysis of the respiratory center and death.
Functional antagonists of curariform drugs are AChE: proserin, physostigmine.
TUBOCURARIN,Tubocurarinichloridum, list "A"
The salt of the alkaloid tubocurarine, in therapeutic doses, blocks Н - ХР of skeletal muscles without significant changes in the basic functions of the body. In large quantities, it can block H - ChR of the adrenal glands and carotid sinus zone, which can lead to a decrease in blood pressure and respiratory depression. In addition, large doses of this substance can promote the release of histamine poison from the cells of the body, which becomes active and can cause bronchospasm.
It is used only in a hospital environment during surgical operations.
PV - ampoules of 2 and 5 ml. 1% solution.
DITILINE,Dithylinum, list "A", "Miorelaxin"
In terms of activity, it is significantly inferior to tubocurarin, the action develops when administered intravenously after 30 seconds and lasts 3 - 7 minutes.
It is used during anesthesia for short-term relaxation of skeletal muscles, and in case of an overdose of this drug, AChE is not used, because they increase the toxicity of ditilin.
PV - amp. 5 and 10 ml of a 2% solution.
Substances with a predominant effect on AR (adrenergic drugs)
These are agents that affect sympathetic adrenergic innervation. .
As a mediator in adrenergic synapses, norepinephrine is most important, which stimulates AR of cell membranes. Synthesis of norepinephrine occurs in the endings (axons) of the sympathetic nerves (i.e., in the postganglionic fibers of the SNS). The starting material for the synthesis of norepinephrine is the amino acid tyrosine, which under the influence of certain enzymes undergoes a number of changes: tyrosine - dioxyphenylalanine (DOPA) - dioxyphenylalanine amine (dopamine) - norepinephrine. This complex biochemical process takes place in adrenergic nerves, and the ultimately formed norepinephrine is deposited in nerve endings in special formations - vesicles. During the arrival of a nerve impulse, part of the norepinephrine is released into the synaptic cleft and excites the AR. The action of the norepinephrine mediator is short-lived, because most of it (80%), after the transmission of the impulse, is re-captured by the nerve endings. Part of the mediator is inactivated by special enzymes: monoamine oxidase (MAO) and catecholortomethyltransferase (COMT).
Distinguish between α-and β-adrenergic receptors, which is due to their different sensitivity to norepinephrine, adrenaline and a number of pharmacological substances. The quantitative ratio in the organs of α - and β - AR is different.
α - AR are 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 radial muscle of the eye.
β-AR are divided into β 1 - and β 2 - AR. Predominantly β 1 -AR are located in the coronary vessels and conductive heart system, β 2 - in the bronchi, vessels of skeletal muscles and the uterus.
Mechanisms of pharmacological action at adrenergic synapses are quite diverse. Some drugs interact with AR of postsynaptic membranes, causing their excitation or depression and corresponding changes in metabolism and cell function. Other drugs act on the endings of the sympathetic nerves and presynaptic membranes. In this case, the drug can disrupt the synthesis of norepinephrine, its deposition in the vesicles, release into the synaptic cleft, reuptake of the mediator by the presynaptic nerve endings. Some substances inhibit the processes of enzymatic inactivation of norepinephrine. Combinations of different mechanisms of action in one drug substance are possible.
CLASSIFICATION of adrenergic drugs.
Adrenomimetics - excitatory AR.
Adrenoblockers - blocking AR.
Sympathomimetics (adrenomimetics indirect action) - do not directly affect AR, but promote the release of norepinephrine from the presynaptic endings and therefore enhance adrenergic reactions.
Sympatholytics - block sympathetic innervation at the level of the endings of the postganglionic sympathetic nerves.
ADRENOMYMETICS
α - β- AM of direct action
A typical representative of this group is
ADRENALIN- is formed from norepinephrine in the cells of the adrenal medulla, by its action and origin it is a steroid hormone. It has a direct stimulating effect on α, β 1, β 2 - AP. In medical practice, it is used in the form
epinephrine hydrochloride solution,SolutioAdrenalinihydrochloridum, list “B”, 1ml.
The effect on organs is expressed by the following pharmacological effects (as in the excitation of the SNS, except for item 7):
1. Expansion of coronary vessels, vessels of skeletal muscles, brain and lungs. In the conditions of the whole organism, the vasoconstrictor effect of adrenaline prevails, which leads to an increase in blood pressure.
2. Strengthening the work of the heart and increased heart rate.
3. The vasoconstriction of the abdominal organs, skin and mucous membranes.
4. Relaxation of the muscles of the bronchi, intestines.
5. Dilation of the pupil as a result of contraction of the radial muscle of the eye.
6. Contraction of the uterus, spleen.
7. Increasing the tone of the sphincters of the gastrointestinal tract and Bladder.
8. Increase in the amount of sugar in the blood as a result of increased metabolism and stimulation of gluconeogenesis.
9. Improving the performance of skeletal muscles by increasing glucose and improving the blood supply to skeletal muscles.
10. Increased secretion of adrenocorticotropic hormone (ACTH).
11. Increasing the amount of free fatty acids in the blood by stimulating lipolysis.
12. Slight excitement of the central nervous system (anxiety, tremor, etc.)
It is applied:
As a vasoconstrictor in shock, collapse, acute hypotension. With intravenous administration, it lasts 5 minutes, with subcutaneous administration - 30 minutes.
With anaphylactic shock and some immediate allergic reactions.
With acute heart weakness, with cardiac arrest (in this case, adrenaline is administered intracardiacally).
For relief of asthma attacks in bronchial asthma (BA).
Together with local anesthetics for vasoconstriction, delaying the absorption of anesthetics and prolonging their action.
In case of insulin overdose or hypoglycemic coma, to restore the amount of sugar in the blood.
Outwardly in ocular practice, ENT - practice for vasoconstriction.
Contraindications for use.
Hypertonic disease.
Atherosclerosis.
Diabetes.
Thyrotoxicosis (increased metabolism).
Pregnancy.
With fluorothane, cyclopropane and chloroform anesthesia (arrhythmia, extrasystoles may occur).
It is prescribed: intravenously, subcutaneously, intramuscularly, intracardiacally, externally. Inside is not assigned, tk. destroyed in the digestive tract.
PV - in ampoules of 1 ml 0.1% solution, it is obtained synthetically or isolated from the adrenal glands of slaughter cattle.
NORADRENALIN,Noradrenalinihydrotartras, list "B"
Unlike adrenaline, it excites mainly α - AR, insignificantly - β 1 - AR, therefore, exhibits a stronger vasoconstrictor effect. Virtually no effect on the bronchi, does not exhibit a hyperglycemic effect, slows down the heart rate. It is used as a vasoconstrictor for shock, collapse, acute hypotension (as a result of trauma, surgery). It is administered intravenously only; better - through a catheter, because causes tissue necrosis due to severe vasospasm. No other routes of injection are used.
Contraindications
Atherosclerosis.
Hypertension.
PV - in ampoules of 1 ml. 0.1% - 0.2% solution.
Curariform remedies
In this section, we will consider substances that block the conduction of excitation in neuromuscular synapses, which leads to relaxation of the striated muscles. Such substances include curare and preparations with curare-like action.
Curare is an arrow poison that the Indians prepared from some species of South American plants and used to poison arrows.
When administered parenterally, curare causes relaxation of skeletal muscles and complete immobilization of the animal. The paralyzing effect of curare on various muscle groups is carried out in a known sequence. First of all, the muscles of the head, neck, limbs are paralyzed, then the muscles of the trunk and, last of all, the diaphragm. At the same time, consciousness is preserved. Death occurs from asphyxia, since breathing stops due to paralysis of the respiratory muscles.
Muscular paralysis caused by curare is reversible and therefore temporary. At the same time, the muscles themselves remain excitable, since with their direct irritation ( electricity... potassium salts) they are reduced. With artificial respiration, animals tolerate large doses of curare and substances similar to it in action. The effect of curare on the muscle is eliminated by the administration of proserin and eserin.
The pharmacological properties of curare were studied by Claude Bernard (1851) and Pelican (1857). The works of these authors have shown that the paralysis of skeletal muscles that occurs after the introduction of curare is peripheral in nature. The experiments were carried out under the following conditions: in the frog, one of the femoral arteries was ligated to turn off the limb from the general circulation, and curare was injected into the abdominal lymphatic sac. Irritation sciatic nerve on the limb with preserved blood circulation did not cause contraction of the limb muscles, while when the stimulation was applied directly to the muscle, the latter contracted. On a limb with a ligated artery, nerve irritation was accompanied by muscle contraction of this limb. Thus, it has been proven that the paralysis caused by curare is due to a peripheral mechanism. Even more convincing results were obtained in experiments on isolated neuromuscular preparations. The experiments were set up as follows: two small cups were yelling; physiological solution was poured into one of them, and physiological solution with the addition of curare was poured into the other. Two isolated neuromuscular preparations were placed in these cups in such a way that the muscle of one of the preparations was immersed in a curare solution, and the nerve trunk - in a saline solution. For another drug, the relationship was reversed: the muscle was in saline, and the nerve was in curare. After some time, irritation of the nerve trunk of the first drug was no longer accompanied by muscle contraction. For the other drug, excitability was completely retained. Direct muscle irritation of both the first and second drugs was accompanied by a normal contractile response.
These experiments confirm that curare blocks neuromuscular transmission.
In large doses, curare inhibits the transmission of nerve impulses in the ganglia of the autonomic nervous system.
Attempts at the clinical use of curare in the treatment of tetanus, epilepsy and other convulsive conditions date back to the second half of the last century. NI Pirogov used curare in patients with tetanus. Curare was widely used by I.P. Pavlov in experiments on animals. However, due to toxic phenomena (due to the variability of the composition, sometimes, instead of a paralyzing effect on the muscles, a convulsive state occurred), curare did not find wide clinical use for a long time.
Interest in curara increased after the alkaloid d-tubocurarine was isolated from it and its structural formula was established. However, tubocurarine, simultaneously with muscle relaxation, in some cases causes a transient decrease in blood pressure by 30-40 mm Hg, which, with repeated administration of tubocurarine or with the introduction of large doses, is already long-term. The drop in blood pressure is apparently due to the fact that tubocurarine promotes the release of histamine. The negative properties of tubocurarine also include bronchospasm caused by it.
Since the synthesis of tubocurarine and its analogs turned out to be extremely difficult, a search began for compounds that would have an effect similar to curare, but were devoid of its negative properties.
The discovery of the fact that there are two quaternary ammonium groups in the tubocurarine molecule gave rise to the creation of quaternary salts of various alkaloids. The role of other chemical groups in the tubocurarine molecule in the manifestation of the active properties of the latter was also studied. Currently, clinical medicine has a number of drugs with a curariform effect.
(CH 3) 3 ≡- (CH 2) n -≡ (CH 3) 3 * 2J -
Studies have shown that the blocking effect of these compounds on neuromuscular conduction is in direct proportion to the length of the polymethylene chain between two quaternary nitrogen atoms. The most active in this series is the compound with ten methylene groups (decamethonium). A further increase in the number of methylene groups in the molecule leads to a decrease in the blocking effect on the conduction of excitation.
The same relationship between the chain length and the strength of the curariform action was found in the series of dicholine esters of aliphatic dicarboxylic acids, as well as some other compounds.
Thus, there was an idea that the most optimal for the manifestation of curariform activity is the distance between two quaternary nitrogen atoms, equal to 10 atoms. This played a positive role in the synthesis of curariform compounds.
Later it was found that some tertiary amines also have a curariform effect. These include alkaloids isolated from various types of larkspur (Delphinium): delsemin, elatin, condelfin, melliktin. These drugs are inferior to d-tubocurarine in strength of curariform action, but less toxic. They are characterized by a more pronounced ganglion-blocking action and efficacy not only for parenteral administration, but also for oral administration, as compared to tubocurarine.
To understand the mechanism of action of curare and curare-like drugs, you need to have an idea of the mechanism of muscle contraction. As you know, a nerve impulse, passing along the motor nerve, contributes to the formation of acetylcholine at the endings of the nerve. The latter, interacting with a receptive substance, causes contraction of the muscle fiber. However, acetylcholine is an unstable substance, it is rapidly hydrolyzed by the enzyme cholinesterase to form choline and acetic acid, it loses its biological activity and the muscle relaxes. A new muscle contraction occurs after it leaves the refractory period, when a new impulse can again cause the release of acetylcholine and subsequent muscle contraction.
According to the modern classification, drugs that block neuromuscular conduction are usually divided into two groups: some of them compete with the action of acetylcholine and prevent its depolarizing effect on the muscle end plates - they are called drugs with a competitive type of action (pachicurare). These include d-tubocurarine, diplacine, paramion, and alkaloids isolated from various species of larkspur. Their mechanism of action is that they reduce the physiological activity of acetylcholine, reducing the sensitivity of n-cholinergic systems to it. The antagonists of this group of substances are eserin, proserin and similar substances. Under the influence of proserin, the cholinesterase enzyme is inactivated, which contributes to the accumulation of the predominant amounts of acetylcholine in the synapse area and the restoration of neuromuscular conduction.
Substances of the second group themselves cause persistent depolarization of the motor end plate. As a result, the physiological alternation of polarization and depolarization of the end plates, carried out using the acetylcholine-cholinesterase system, becomes impossible. The representative of this group is ditylin. Neurin is not an antidote for them. On the contrary, by inactivating cholinesterase, it enhances their action. These substances are called drugs with a depolarizing type of action ("leptocurare").
The type of action of drugs is to a certain extent related to their chemical structure. It is noted that substances of the second group have a predominantly linear structure. The strength of their action depends on the length of the polymethylene chain. When heterocyclic compounds are introduced into the molecule (instead of part of the polymethylene chain), substances are formed that, according to the mechanism of action, approach alpha-tubocurarine. A similar result is observed when the methyl groups at the quaternary nitrogen atoms are replaced by ethyl, butyl, benzyl, and nitrobenzyl groups. The symmetrical structure of the molecule is typical for all bisammonium compounds with the strongest curariform action.
Practical application of drugs with curariform action was found mainly in anesthesiology. One of the essential defects of some types of anesthesia is insufficient relaxation of the skeletal muscles. Muscular tone largely depends on the functional state of the central nervous system, in particular spinal cord... The anesthetist is often forced to use significant amounts of the drug to deepen the anesthesia only in order to achieve a complete elimination of muscle tone, and this is not always possible. Only when using curariform drugs does the flow of impulses from the central nervous system to the muscles completely stop. In this regard, in last years curariform drugs are used in surgery, in combination with inhalation and non-inhalation anesthesia. In this case, on the one hand, there is an increase in their action, on the other hand, anesthesia is accompanied by complete relaxation of the muscles, which has a favorable effect on the outcome of the operation and on the course of the postoperative period. The combined use of ether with cure-like drugs leads to potentiation of the action, which allows much less ether to be consumed for the operation.
As you know, during anesthesia with nitrous oxide, there is no sufficient relaxation of the muscles. When combined with curariform drugs, this nitrous oxide deficiency is eliminated, which makes it possible to carry out long complex operations under this anesthesia.
Using curariform drugs for anesthesia, it is necessary to create all conditions for artificial respiration due to possible respiratory arrest. In most cases, these drugs are used for intubation anesthesia, when the risk of respiratory arrest is largely eliminated.
In some operations on the organs of the chest cavity (lungs, heart, esophagus), when there is a threat of bilateral pneumothorax, curariform drugs are prescribed in doses that turn off natural respiration, and the patient is transferred to "controlled artificial respiration", carried out using special equipment in the rhythm of natural respiration when oxygen and drugs are rhythmically supplied to the lungs.
In addition, curariform drugs are used in psychiatry for electroconvulsive therapy (in the treatment of schizophrenia), which makes it possible to prevent traumatic injuries in patients (fractures, dislocations) that occur under the influence of muscle contractions during the switching on of the current.
In the nervous clinic, curariform drugs are used for diseases of the central nervous system, accompanied by an increased tone of skeletal muscles (muscle hypertension).
Curariform drugs, weakening muscle tone, create favorable conditions for the implementation of motor acts.
Recently, curariform drugs have been used to treat post-traumatic tetanus in combination with other types of therapy.
Among the drugs of this group used in surgical practice is diplacin - 1,3-di-β-platinum-ethoxy) benzene dichloride.
In terms of the strength of action, diplacin is inferior to tubocurarine, but it compares favorably with it in its greater therapeutic breadth. Respiratory arrest is observed when using doses that are 2-3 times higher than doses that cause relaxation of skeletal muscles. In terms of the duration of action, diplacin is inferior to tubocurarine. The effect develops within 2-3 minutes after intravenous administration of the drug and lasts 20-25 minutes. If necessary, to cause prolonged relaxation of the muscles, diplacin is reintroduced, while the possibility of some summation of the action is not excluded. In some individuals, an increased sensitivity to diplacin has been noted, when small doses of the drug cause respiratory arrest. The introduction of diplacin is allowed if there is the possibility of immediate intubation for artificial respiration if it stops.
Meso-3,4-diphenylhexane-bis-n-trimethylammonium diiodide - is many times more potent than diplacin. The action of paramion on muscles develops in 2-3 minutes and lasts 30-60 minutes. Blood pressure under the influence of paramion rises slightly (by 5-10 mm Hg). Like other drugs in this group, paramion, with hypersensitivity to it, in some individuals can cause respiratory arrest.
Delsemin- an alkaloid isolated from various Central Asian species of larkspur (Delphinium semibarbatum, Delphiniumi rotundifolium, etc.) It, like tubocurarine, reduces the sensitivity of n-cholinergic systems of skeletal muscles to acetylcholine, being a competitive antagonist of the latter. Delsemin has a gantlioblocking effect, therefore, with its introduction, a decrease in blood pressure occurs. In this regard, ephedrine (up to 1%) is added to delsemin solutions, which has the ability to increase blood pressure.
Delsemin is mainly used for intratracheal anesthesia with ether and nitrous oxide to relax muscle tone and turn off natural breathing during surgical operations. With ether anesthesia, delsemin is consumed relatively less than with nitrous oxide anesthesia. The drug is administered intravenously in doses of 0.2-2 mg / kg, and at first about 1/3 of the total dose is administered in order to identify the patient's reaction, and then after 3-4 minutes - the rest, provided that there are no side reactions. The effect of a single dose lasts about an hour. With repeated administration of delsemin, its effect is enhanced. With the introduction of large doses, respiratory depression is possible due to a decrease in the function (up to paralysis) of the respiratory muscles (Table 2).
In case of an overdose, intravenous proserin is used in combination with atropine, artificial respiration, oxygen inhalation.
Other drugs in this group - elatin, condelfin and melliktin - are less effective, but have a more prolonged paralyzing effect on skeletal muscles. They show their effect when taken orally and are mainly used in nervous diseases. Treatment is carried out in courses. According to the mechanism of action, they belong to drugs with a competitive type of action.
Elatin- an alkaloid isolated from high larkspur (Delphinium elatum L.), inhibits neuromuscular conduction, as well as conduction of excitation in the ganglia, reducing the sensitivity to acetyl-choline of n-cholinergic systems, also has a depressing effect on the subcortical centers. The drug has some hypotensive effect. Effective when administered orally as well as parenterally. The action of elatine can be removed by its antagonist - proserin. Elatin is recommended for use mainly in neurological practice for diseases of the central nervous system, accompanied by increased muscle tone. When taking the drug, the general condition improves, muscle tension decreases and the intensity of pain in the extremities decreases. Treatment is carried out in courses in combination with other methods of treatment.
Condelfin isolated from the plant tangled larkspur (Delphinium confusum). In terms of pharmacological properties, it is close to elatin: as effective as elatin, when taken orally and when administered parenterally. Indications for use are the same as for elatin. The dosage of condel-fin and the duration of treatment are determined depending on the effect caused and the patient's tolerance of the drug.
Melliktin- iodine hydrate of methyllycaconitine - an alkaloid found in various types of larkspur. It has the same pharmacological properties as condelfin and elatin and is prescribed for the same diseases. In the event of side effects, the same measures are taken as when using other curariform drugs of this group.
Ditilin- diiodide of dicholine ester of succinic acid, refers to drugs with a depolarizing type of action and is distinguished by its short duration.
The introduction of 1-1.5 ml of a 1% solution of ditilin causes a short-term relaxation of the muscles lasting 5-7 minutes. In the body, under the influence of cholinesterase, it rapidly decomposes into choline and succinic acid... Neurin is not an antagonist of ditilin and, on the contrary, enhances its effect by blocking cholinesterase. Re-introduction of ditilin leads to an increase in its action.
In some patients, under the influence of ditilin, prolonged respiratory depression occurs, sometimes with a fatal outcome. It is possible that the reason for the latter is the low initial level of cholinesterase in the patient's blood before the administration of ditilin.
Drugs
(Diplacinum) (A). With intubation anesthesia, it is administered intravenously in doses of 0.08-0.15 g in combination with sodium thiopental (0.3-0.6 g in the form of a 2.5% solution).
For long-term operations, 50% of the initial dose of diplacin is re-administered. To turn off natural breathing, large doses are used (0.2 g or more). Produced in ampoules containing 5 ml of 2% diplacin solution.
(Paramyonum) (A). White crystalline powder, soluble in cold water up to 0.5%. When combined with nitrous oxide, 4-5 ml of a 0.1% solution is administered intravenously; if necessary, turn off active breathing, the dose is doubled. For ether anesthesia, it is used in smaller doses (1.5-2 ml of a 0.1% solution).
Delsemin(Delseminum) (A). White crystalline powder, soluble in water 1: 800. It is administered intravenously under anesthesia with nitrous oxide in doses of 0.5-2 mg / kg, to turn off natural respiration -5-6 mg / kg. With ether anesthesia, the dose of the drug is reduced. When mixing solutions of barbiturates with solutions of delsemin, a precipitate forms.
Elatin(Elatinum) (A). White crystalline powder, slightly soluble in water. Administered orally in powders and tablets 3-5 times a day, 0.01 g; the course of treatment is 20-30 days. The effect develops in 1-7 days. During treatment, close medical supervision is necessary.
Condelfin(Condelphinum) (A). Fine crystalline white powder, insoluble in water. It is administered orally at a dose of 0.025 g once a day, in the future, the number of doses, depending on the tolerance of the drug, can be increased to three. The course of treatment is 10-12 days.
Melliktin(Mellictinum) (A). White crystalline powder. Apply orally 0.02 g 1-5 times a day. The course of treatment is from 3 weeks to 2 months.
Ditilin(Ditilinum) (A). White crystalline powder, readily soluble in water. It is used for anesthesia with nitrous oxide, ether, sodium thiopental intravenously, 1-1.5 ml of a 1% solution. If necessary, a longer effect and in the presence of artificial respiration, ditilin is re-injected with 10-20 ml of 1 or 2% solution. With respiratory depression, artificial respiration, blood or erythrocyte mass transfusion are performed.
Long-acting ganglion blockers.
Short-acting ganglion blockers.
Gigronium (Hygronium).
Application: in anesthesiology to create artificial hypotension. Enter in / in (drip) 0.01% solution in isotonic sodium chloride solution or 5% glucose solution.
Side effects: severe hypotension.
Release form: powder of 0.1 g in an ampoule with a capacity of 10 ml No. 10. List B.
Benzohexonium (Benzohezonium).
Application: peripheral vascular spasm, hypertension, hypertensive crises, bronchial asthma, gastric ulcer and duodenum... Assign inside 0.1–0.2 g 2-3 times a day, s / c, i / m - 1–1.5 ml of a 2.5% solution. VRD - inside 0.3 g; V.S.D. - 0.9 g; s / c one-time - 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: are similar to benzohexonium.
Release form: in ampoules of 1 and 2 ml of a 5% solution.
Pachikarpina hydroiodide (Pachycarpini hydroiodidum).
Application: with spasms of peripheral vessels and to stimulate labor, to reduce bleeding in the postpartum period. Assign inside, s / c, i / m.
Contraindications: pregnancy, severe hypotension, liver and kidney disease.
Release form: Available in 0.1 g tablets, 2 ml ampoules of a 3% solution. It is dispensed only with a doctor's prescription. List B. This group includes pirylene tablets ( Pirilenum) and temekhin ( Temechinum) by 0.005 g.
Curariform substances block the n-cholinergic receptors of skeletal muscles and cause relaxation of skeletal muscles (muscle relaxants). According to the mechanism of action, they are divided into substances:
1) antidepolarizing (competitive) type of action (tubocurarine, diplacin, meliktin);
2) depolarizing type of action (ditilin);
3) mixed type of action (dioxonium).
According to the duration of action, muscle relaxants are divided into three groups:
1) short-acting (5-10 min) - ditilin;
2) medium duration (20–40 min) - tubocurarine chloride, diplacin;
3) long-acting (60 minutes or more) - anatruxonium.
Tubocurarine-chloride (Tubocurarini-chloridum).
It is a curariform drug with an anti-depolarizing effect.
Application: in anesthesiology for muscle relaxation. Injected intravenously at 0.4-0.5 mg / kg. During the operation, the dose is up to 45 mg.
Side effects: respiratory arrest is possible. To weaken the effect of the drug, proserin is administered.
Contraindications: myasthenia gravis, severe kidney and liver disorders, old age.
Release form: in ampoules of 1.5 ml, containing 15 mg of preparation No. 25.
Ditilin (Dithylinum), listenone (Lysthenon).
Short-acting synthetic 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: respiratory depression is possible.
Contraindications: glaucoma. Ditilin solutions should not be mixed with barbiturates and donated blood.
Release form: ampoules of 5 ml of 2% solution No. 10.
In anesthetic practice, other drugs are also used: arduan ( Arduan), pavulon ( Pavulon), norkuron ( Norcuron), trarium ( Tracrium), melliktin ( Mellictin). M-, n-cholinolytics have a blocking effect on m- and n-cholinergic receptors. Among them there are substances that block mainly peripheral m- and n-cholinergic receptors (peripheral m-, n-cholinolytics, or antispasmodics) and have an antispasmodic effect. These are spasmolitin, typhene, etc. There are also drugs that penetrate the blood-brain barrier and block the m- and n-cholinergic receptors of the central nervous system, used to treat mainly Parkinson's disease (cyclodol, dinesin). In addition, there are drugs with a central and peripheral m- and n-anticholinergic effect, such as aprofen.
Spasmolitin (Spasmolythinum).
Peripheral m-, n-anticholinergic, which has an antispasmodic effect.
Application: endarteritis, pylorospasm, spastic colic, gastric ulcer and duodenal ulcer. Assign inside, 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 that requires a quick mental and physical reaction.
Release form: powder.
1) means of non-depolarizing action;
2) means of depolarizing action.
Curare, a specially processed sap of a South American plant, has long been used by the 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 due to the cessation of the transmission of excitation from the motor nerves to the skeletal muscles.
The main active substance curare - alkaloid d-tubocurarine. At present, many other curariform preparations are also known.
Indications for the use of all muscle relaxants:
Curariform drugs are used for surgical operations to relax skeletal muscles.
For mechanical ventilation during surgery
Reduction of dislocations, reduction of bone fragments
Convulsions
NON-DEPOLARIZING MIORELAXANTS.
Tubocurarine chloride, pipcuronium bromide, pancuronium bromide. These drugs, when administered intravenously, cause rapid relaxation of the skeletal muscles, lasting 30-60 minutes. First, the muscles of the head and neck are relaxed, then the limbs, vocal cords, trunk and, last of all (at high doses), respiratory (intercostal and diaphragm muscles), which leads to respiratory arrest. They do not act on the central nervous system, since they poorly pass the blood-brain barrier.
Mechanism of action
Antidepolarizing muscle relaxants, by binding to the H-cholinergic receptor, cover (screen) it from the effects of synaptic acetylcholine. As a result, the nerve impulse will not cause depolarization of the muscle fiber membrane (therefore, drugs are called non-depolarizing).
These compounds compete (competitive muscle relaxants) with acetylcholine for H-cholinergic receptors of the postsynaptic membrane: with an increase in the amount of acetylcholine in the synapse (for example, with the introduction of anticholinesterase drugs), the mediator displaces the muscle relaxant from the connection with the membrane and itself forms a complex with the receptor, causing depolarization.
Antagonists antidepolarizing (competitive) muscle relaxants are anticholinesterase agents (proserin, etc.), which, by inhibiting synaptic cholinesterase (an enzyme that breaks down acetylcholine), contribute to the accumulation of acetylcholine. They are used for overdose of non-depolarizing muscle relaxants.
Indications for use
For major surgical interventions for long-term relaxation of the muscles.
In addition, they are used to relieve seizures in patients with severe tetanus.
Non-depolarizing drugs can cause side effect- lowering blood pressure by blocking the H-cholinergic receptors of the ganglia.
DEPOLARIZING MYORELAXANT
suxamethonium chloride, iodide (ditilin) is widely used in medical practice.
Mechanism of action
Due to its great structural similarity with acetylcholine, it not only binds the H-cholinergic receptor of skeletal muscle (by analogy with tubocurarine), but also excites it, causing depolarization of the postsynaptic membrane (like acetylcholine). Unlike acetylcholine, which is instantly destroyed by cholinesterase, ditilin gives persistent depolarization: after a short (several seconds) contraction, the muscle fiber relaxes, and its H-cholinergic receptors lose sensitivity to the mediator. The action of ditilin ends in 5-10 minutes, during which it is washed out from the synapse and hydrolyzed by pseudocholinesterase.
Naturally, anticholinesterase agents, promoting the accumulation of acetylcholine, lengthen and enhance the effect of depolarizing muscle relaxants.
Applicable ditilin for short-term muscle relaxation during tracheal intubation, reduction of dislocations, bone reposition in fractures, bronchoscopy, etc.
Side effects:
1) postoperative muscle pain. At the beginning of depolarization, muscle fibrillar contractions, twitching appear, they are the cause of postoperative muscle pain;
2) increased intraocular pressure;
3) violation of the rhythm of cardiac activity. In case of an overdose of ditilin, fresh (high pseudocholinesterase activity) blood is transfused and electrolyte disturbances are corrected. The use of muscle relaxants is permissible only if there are conditions for tracheal intubation and mechanical ventilation.
ATROPINE Solutio Atropini sulfatis 1%for i / v, i / m or n / a introduction, tablets, eye drops (1%)
Application: - spasms of the intestines and bile and urinary tract, pylorospasm, bradyarrhythmias, for premedication, poisoning with phosphorus-poisoning agents, during X-ray studies of the gastrointestinal tract,
Examination of the fundus (rare) to create functional rest at inflammatory diseases and eye injuries, gastric ulcer and duodenal ulcer, bronchial asthma, bronchitis with mucus hyperproduction.
Side effects: mydriasis, accommodation paralysis, tachycardia, intestinal and bladder atony, headache, dizziness, loss of touch.
This name was given to a group of drugs that, due to the suppression of neuromuscular transmission, like curara poison, cause paralysis of skeletal muscles.Curare venom is a mixture of alkaloids found in plants of the Strychnos and Chondrodendron families.
In their composition, these alkaloids have a quaternary or tertiary ammonium group. The main representative of the alkaloids contained in curar is D-tubocurarine. The beginning of the clinical use of curare dates back to 1932, when highly purified curare fractions were used for the relief of tetanus seizures and the treatment of spastic disorders, and later it was used as an adjuvant medication in shock therapy of mental disorders.
For the first time, curare as a means of causing muscle relaxation during general anesthesia was used by G. Griffiths and E. Johnson in 1942. Since then, surgery has become the main field of application of peripheral muscle relaxants in medical practice. Later, a dimethylated tubocurarine derivative was introduced into clinical practice, which exceeded its predecessor by 3 times in muscle relaxant properties.
According to the mechanism of formation of the neuromuscular block, peripheral muscle relaxants can be divided into non-depolarizing agents (tubocurarine, atracurium, vecuronium, mivacurium, pancuronium, pypecuronium, rocuronium, tolpirezol, prestonal) and depolarizing agents (mice> rabbits>> cats
anticholinesterase drugs for blockade
excitation
However, the selectivity in relation to muscle n-cholinergic receptors in curariform drugs is not absolute, some of them are active against ganglionic receptors, although they differ in their ability to block autonomic ganglia. Tubocurarine causes a small blockade of the ganglia and chromaffin cells of the adrenal medulla, which can cause a decrease in blood pressure.
Depolarizing curariform drugs have a similar property. Suxamethonium selectively blocks the cardiac branch of the vagus, which can cause the development of sinus tachycardia, arrhythmias and increased blood pressure. Pancuronium and pipcuronium in doses used in the clinic have practically no effect on the ganglia.
Some curariform drugs (tubocurarine, decametonium) are capable of provoking the release of histamine from mast cells, which causes hypotension, bronchospasm, hypersecretion of the bronchial and salivary glands. Histamine is released due to degranulation of mast cells, therefore, along with histamine, heparin is released from them, which leads to a decrease in blood clotting. The histamine-releasing effect of curariform drugs is not associated with their n-anticholinergic properties, but is due to the fact that representatives of this group are bases.
Increased histamine levels and blockade of autonomic ganglia are seen as the main cause. side effects curariform funds. But a decrease in blood pressure with the rapid introduction of these drugs can be the result of muscle relaxation and, as a result, deterioration of venous outflow from them.
More severe complications can occur with the use of depolarizing muscle relaxants. Persistent depolarization of the muscle cell membrane leads to the release of K + from it and, as a consequence, to an increase in its concentration in plasma. This can have adverse consequences in trauma patients, especially in burns and wounds when muscle innervation is impaired. Denervation causes an increase in the number of n-cholinergic receptors in the muscle (not only in the end plate region), therefore, large surfaces of the muscle fiber membrane become sensitive to suxamethonium. Hyperkalemia, in turn, can cause ventricular arrhythmias and even cardiac arrest.
Moreover, if usually the action of suxamethonium lasts 5 minutes (it is rapidly destroyed by blood esterases), then in patients with esterase deficiency, muscle paralysis can be significantly prolonged. The reasons for the deficiency of this group of enzymes are different: in newborns or patients with liver diseases, the synthesis of esterases is not intensive enough, in addition, their absence can be genetically determined.
The introduction of suxamethonium (sometimes other curariform drugs) can provoke the development of malignant hyperthermia, which is also due to hereditary factors - mutation of Ca 2+ - channels of the sarcoplasmic reticulum. The release of Ca 2+ from the depot causes severe muscle spasm and an increase in temperature. The mortality rate from such hyperthermia reaches 65%. In these cases, it is necessary to introduce dantrolene, which prevents the release of Ca 2+ from the depot and thereby contributes to muscle relaxation.
Antagonists of non-depolarizing agents are anticholinesterase agents (neostigmine). The action of depolarizing muscle relaxants can be stopped or reduced by the administration of fresh citrated blood containing pseudocholinesterase, which accelerates their hydrolysis.
Curariform drugs are poorly absorbed from the gastrointestinal tract, so they are usually administered intravenously. They are used to achieve muscle relaxation in anesthesiology during operations, during broncho-, laryngo- and esophagoscopy, in case of poisoning with convulsive poisons, for the relief of acute convulsions in tetanus and epilepsy, as well as for diagnostic purposes for the differentiation of muscle spasm and dysfunction of the osteoarticular apparatus.
Below are the individual curariform drugs that are used in the clinic.
Atracuria besilate (Atracurium besilate). Relaxation of the muscles during surgery, endotracheal intubation, mechanical ventilation (as an addition to general anesthesia).
Vecuronium bromide (Vecuronium bromide). Muscle relaxation during mechanical ventilation during general anesthesia and intensive care (tetanus, acute respiratory failure).
Isociuronium bromide (Isociuronium bromide). Muscle relaxation during mechanical ventilation during general anesthesia and intensive care (tetanus, acute respiratory failure).
Mivacuria chloride (Mivacurium chloride). Relaxation of skeletal muscles during general anesthesia to facilitate tracheal intubation and mechanical ventilation.
Pancuronium bromide (Pancuronium bromide). The need for muscle relaxation when carrying out various kinds of surgical interventions using a ventilator.
Pipecuronium bromide (Pipecuronium bromide). Muscle relaxation during surgery, endotracheal intubation.
Suxamethonium chloride. Relaxation of muscles during surgical interventions: reduction of dislocations, reposition of bone fragments; electro-impulse therapy.
Tolperisone (Tolperisone). Conditions accompanied by hypertonicity of skeletal muscles against the background of organic neurological damage (damage to the pyramidal tract, multiple sclerosis, myelopathy, encephalomyelitis, muscle spasm, muscle hypertonicity, muscle contractures, spinal automatism), extrapyramidal disorders (atherencephalic vascular disease) obliterating vascular diseases (obliterating atherosclerosis of the vessels of the extremities, obliterating endarteritis, systemic scleroderma, obliterating thromboangiitis, diabetic angiopathy, Raynaud's syndrome), including against the background of vascular innervation disorders, post-thrombotic disorders of blood and lymph circulation; in pediatrics - Little's disease (infantile spastic paralysis).
Cisatracurium besilate (Cisatracurium besilate). Maintaining relaxation of skeletal muscles and carrying out tracheal intubation during operations and mechanical ventilation in intensive care units.