Cholinomimetic agents. M- and N-cholinomimetics (anticholinesterase drugs) Agents affecting efferent innervation
CHOLINERGICS
In cholinergic synapses (parasympathetic nerves, preganglionic sympathetic fibers, ganglia, all somatic) the transmission of excitation is carried out by the mediator acetylcholine. Acetylcholine is formed from choline and acetylchoenzyme A in the cytoplasm of the endings of cholinergic nerves.
Cholinergic receptors excited by acetylcholine have unequal sensitivity to certain pharmacological agents. This is the basis for the identification of the so-called: 1) muscarine-sensitive and 2) nicotine-sensitive cholinergic receptors, that is, M- and N-cholinergic receptors. M-cholinergic receptors are located in the postsynaptic membrane of effector organ cells at the endings of postganglionic cholinergic (parasympathetic) fibers, as well as in the central nervous system (cortex, reticular formation). H-cholinergic receptors are located in the postsynaptic membrane of ganglion cells at the endings of all preganglionic fibers (in the sympathetic and parasympathetic ganglia), the adrenal medulla, the sinocarotid zone, the end plates of skeletal muscles and the central nervous system (in the neurohypophysis, Renshaw cells, etc.). The sensitivity of different H-cholinergic receptors to pharmacological substances is not the same, which makes it possible to distinguish H-cholinergic receptors of ganglia and H-cholinergic receptors of skeletal muscles.
MECHANISM OF ACETYLCHOLINE By interacting with cholinergic receptors and changing their conformation, tylcholine changes the permeability of the postsynaptic membrane. With the excitatory effect of acetylcholine, Na ions penetrate into the cell, leading to depolarization of the postsynaptic membrane. This is manifested by a local synaptic potential, which, having reached a certain value, generates an action potential. Local excitation, limited to the synaptic region, spreads throughout the cell membrane (second messenger - cyclic guanosine monophosphate - cGMP).
The action of acetylcholine is very short-lived; it is destroyed (hydrolyzed) by the enzyme acetylcholinesterase.
Drugs can affect the following stages of synaptic transmission:
1) synthesis of acetylcholine;
2) the process of releasing the mediator;
3) interaction of acetylcholine with cholinergic receptors;
4) enzymatic hydrolysis of acetylcholine;
5) capture by presynapric endings of choline formed during the hydrolysis of acetylcholine.
CLASSIFICATION OF CHOLINERGIC DRUGS
I. M-, N-cholinomimetic agents
Acetylcholine
Carbocholine
II. M-cholinomimetic agents (anticholinesterase agents, AChE) a) reversible action
Prozerin - galantamine
Physostigmine - oxazil
Edrophonium - pyridostigmine b) irreversible action
Phosphacol - Armin
Insecticides (chlorophos, karbofos, dichlorvos)
Fungicides (pesticides, defoliants)
Chemical warfare agents (sarin, zaman, tabun)
III. M-cholinomimetics
Pilocarpine
Aceclidine
Muscarine
IV. M-cholinergic blockers (drugs of the atropine group) a) not
lective
Atropine - scopolamine
Platiphylline - metacin
b) selective (M-one - anticholinergics)
Pirenzipine (gastrocepin)
V. N-cholinomimetics
Cititon
Lobelin
Nicotine
VI. N-anticholinergics
a) ganglion blockers
Benzohexonium - pyrylene
Gigroniy - harfonade
Pentamin
b) muscle relaxants
Tubocurarine - pancuronium
Anatruxonium - ditilin
Let's look at a group of drugs related to M-, N-cholinomimetics. Drugs that directly stimulate M- and H-cholinergic receptors (M-, H-cholinomimetics) include acetylcholine and its analogues (carbacholine). Acetylcholine, a mediator in cholinergic synapses, is an ester of choline and acetic acid and belongs to monoquaternary ammonium compounds.
It is practically not used as a medicine, since it acts sharply, quickly, almost with lightning speed, and for a very short time (minutes). When taken orally, it is ineffective as it hydrolyzes. In the form of acetylcholine chloride, it is used in experimental physiology and pharmacology.
Acetylcholine has a direct stimulating effect on M- and H-cholinergic receptors. With the systemic action of acetylcholine (iv administration is unacceptable, since blood pressure sharply decreases), M-cholinomimetic effects predominate: bradycardia, vasodilation, increased tone and contractile activity of the muscles of the bronchi and gastrointestinal tract. The listed effects are similar to those observed when the corresponding cholinergic (parasympathetic) nerves are irritated. The stimulating effect of acetylcholine on N-cholinergic receptors of the autonomic ganglia also occurs, but it is masked by the M-cholinomimetic effect. Acetylchline also causes a stimulating effect on H-cholinergic receptors in skeletal muscles.
In connection with the above, in the future we will focus on anticholinesterase drugs. Anticholinesterase drugs (AChE) are drugs that exert their effect by inhibiting, blocking acetylcholinesterase. Inhibition of the enzyme is accompanied by the accumulation of the mediator acetylcholine in the area of the synapse, that is, in the area of cholinoreactive receptors. Under the influence of anticholinesterase drugs, the rate of destruction of acetylcholine slows down, which exhibits a longer-lasting effect on Mi N-cholinergic receptors. Thus, these drugs act similarly to M, N-cholinomimetics, but the effect of anticholinesterase drugs is mediated through endogenous (own) acetylcholine. This is the main mechanism of action of anticholinesterase drugs. It should be added that these drugs also have some direct stimulating effect on M, N-cholinergic receptors.
Based on the persistence of the interaction of anticholinesterase drugs with acetylcholinesterase, they are divided into 2 groups:
1) AChE agents of reversible action. Their effect lasts 2-10 hours. These include: physostigmine, proserine, galantamine and others.
2) AChE agents of irreversible action. These drugs bind very powerfully to acetylcholinesterase for many days, even months. However, gradually, after about 2 weeks, enzyme activity can be restored. These agents include: armin, phosphakol and other anticholinesterase agents from the group of organophosphorus compounds (insecticides, fungicides, herbicides, BOV).
The reference agent of the group of reversibly acting AChE agents is PHYSOSTIGMINE (it was used for a long time as a weapon and as a means of justice, since according to legend, only the truly guilty person dies from the poison), which is a natural alkaloid from Calabar beans, i.e. dried mature seeds of Western -African climbing tree Physotigma venenosum. In our country, PROSERIN is more often used (tablets of 0.015; ampoules of 1 ml 0.05%, in ophthalmic practice - 0.5%; Proserinum), which, like other drugs in this group (galantamine, oxazil, edrophonium, etc. .), a synthetic compound. Prozerin's chemical structure is a simplified analogue of physostigmine, containing a quaternary ammonium group. This distinguishes it from physostigmine. Due to the unidirectional action of all of these drugs, they will have almost common effects.
Of significant practical interest is the influence of AChE agents, both natural and synthetic, on certain functions:
2) tone and motility of the gastrointestinal tract;
3) neuromuscular transmission;
4) bladder;
First of all, we will analyze the effects of proserin associated with its effect on M-cholinergic receptors. Anticholinesterase drugs, in particular proserin, affect the eye as follows:
a) cause constriction of the pupil (miosis - from the Greek - myosis - closure), which is associated with co-mediated excitation of M-cholinergic receptors of the circular muscle of the iris (m. sphincter purillae) and contraction of this muscle;
b) reduce intraocular pressure, which is the result of miosis. At the same time, the iris becomes thinner, the angles of the anterior chamber of the eye open to a greater extent, and therefore the outflow (reabsorption) of intraocular fluid through the Fontan spaces and Schlemm’s canal improves.
c) proserin, like all AChEs, causes a spasm of accommodation (adaptation). In this case, the drugs indirectly stimulate the M-cholinergic receptors of the ciliary muscle (m. ciliaris), which has only cholinergic innervation. Contraction of this muscle relaxes the ligament of Zinn and, accordingly, increases the curvature of the lens. The lens becomes more convex, and the eye is set to the near point of vision (distance vision is poor). Based on the above, it becomes clear why prozerin is sometimes used in ophthalmic practice. In this regard, prozerin is indicated for open-angle glaucoma (0.5% solution, 1-2 drops 1-4 times a day).
Prozerin has a stimulating effect on the tone and motor activity (peristalsis) of the gastrointestinal tract, thereby improving the movement of contents, enhancing the tone of the bronchi (causing bronchospasm), as well as the tone and contractile activity of the ureters. In a word, AChE, in particular proserin, enhance the tone of all smooth muscle organs. In addition, prozerin enhances the secretory activity of the exocrine glands (salivary, bronchial, intestinal, sweat) due to acetylcholine.
THE CARDIOVASCULAR SYSTEM. Proserine usually reduces heart rate and tends to lower blood pressure.
The use of prozerin in clinical practice is associated with its listed pharmacological effects. Due to its tonic effect on the tone and contractile activity of the intestines and bladder, the drug is used to eliminate postoperative atony of the intestines and bladder. It is prescribed in the form of tablets or injections under the skin.
EFFECTS OF PROSERIN (AChE) WHEN EFFECTING ON N-CHOLINORECEPTORS (NICOTINE-LIKE EFFECTS). Nicotine-like effects of prozerin are manifested in relief:
1) neuromuscular transmission
2) transmission of excitation in the autonomic ganglia. As a result, prozerin causes a significant increase in the force of contraction of skeletal muscles, and due to this it is indicated for use in patients with myasthenia gravis. Miasthenia gravis is a neuromuscular disease with two characteristic processes occurring in parallel:
a) damage to muscle tissue such as polymyositis (autoimmune disorders);
b) damage to synaptic conduction, synaptic block (less synthesis of Acetylcholine, difficulty in its release, insufficient sensitivity of receptors). Clinic: muscle weakness and severe fatigue. In addition, the drug is used in neurological practice for paralysis, paresis that occurs after mechanical injuries, after polio (residual effects), encephalitis, optic neuritis, and neuritis. Due to the fact that prozerin facilitates the transmission of excitation in the autonomic ganglia, it is indicated for poisoning with ganglion blockers. In addition, prozerin is effective in case of overdose of muscle relaxants (muscle weakness, respiratory depression) with antidepolarizing action (iv up to 10-12 ml of 0.05% solution), for example d-tubocurarine. Sometimes prozerin is prescribed for weak labor (used to be more common, now very rarely). As you can see, the drug has a wide range of activities, and therefore there are side reactions.
Side effects: the effect of a single dose of proserin appears after 10 minutes and lasts up to 3-4 hours. In case of overdose or hypersensitivity, there may be such undesirable reactions as increased intestinal tone (even diarrhea), bradycardia, bronchospasm (especially in people prone to this).
The choice of AChE drugs is determined by their activity, ability to penetrate tissue barriers, duration of action, presence of irritant properties, and toxicity. For glaucoma, prozerin, physostigmine, and phosphakol are used. It should be emphasized that galantamine is not used for this purpose, as it is irritating and causes swelling of the conjunctiva. GALANTAMINE - an alkaloid of the Caucasian snowdrop - has almost the same indications for use as prozerin. Due to the fact that it penetrates the BBB better (tertiary amine, not quaternary, like proserine), it is more indicated in the treatment of residual effects after polio.
For resorptive action, PYRIDOSTIGMINE and OXAZIL are prescribed (that is, actions after absorption), the effect of which is longer than that of proserine. Contraindications: epilepsy, hyperkinesis, bronchial asthma, angina pectoris, atherosclerosis, in patients with swallowing and breathing disorders.
SECOND GROUP OF AChE DRUGS - AChE means of “irreversible” type of action. Here, in essence, there is one medicine, an organophosphorus compound - an organic ester of phosphoric acid - PHOSPHAKOL. Phosphacolum - 10 ml bottles of 0.013% and 0.02% solutions. The drug is characterized by the highest toxicity, therefore it is used only topically in ophthalmic practice. Hence the indications for use:
1) acute and chronic glaucoma;
2) when the cornea is perforated; loss of the lens (artificial lens, long-term miosis is needed). The pharmacological effects are the same as those of prozerin in relation to the eye. It should be said that in ophthalmology, solutions of proserin and phosphakol are currently rarely used.
The second drug is Armin (Arminum) - an ester of ethylphosphonic acid, FOS is included in the group of potent, long-lasting drugs. Other FOS are of significant interest to the doctor. It has high toxicity (hyperactivation of cent-ac insecticides, fungicides, herbicides, as it is essential for the oral and peripheral cholinergic systems). In small cases, the number of poisonings with these substances has come to an end. concentrations is used as a local miotic and antiglaucomatous Pharmacological effects of organic phosphorus compounds drug. Available in the form of eye drops (0.01% solution, 1-2 drops, accumulation of endogenous (own) acetylcholine in the tissue 2-3 times a day). a consequence of persistent inhibition of acetylcholinesterase. Acute Other OPs, such as insecticides, fungicides, and herbicides, are of significant interest to the doctor, since the number of poisonings with these substances has increased significantly.
The pharmacological effects of organic phosphorus compounds are due to the accumulation of endogenous (total) acetylcholine in tissues due to persistent inhibition of acetylcholinesterase. Acute OP poisoning requires immediate assistance.
SIGNS OF POISONING BY PHOS AND ACHE SUBSTANCES IN GENERAL. OPC poisoning has a very characteristic clinical picture. The patient's condition is usually serious. Muscarinic and nicotine-type effects are noted. First of all, the patient is found to have:
1) pupillary spasm (miosis);
2) severe spasm of the gastrointestinal tract (tenesmus, abdominal pain, diarrhea, vomiting, nausea);
3) severe bronchospasm, suffocation;
4) hypersecretion of all glands (salivation, pulmonary edema - gurgling, wheezing, feeling of tightness in the chest, shortness of breath);
5) the skin is wet, cold, sticky.
All of these effects are associated with stimulation of M-cholinergic receptors (muscarinic effects) and correspond to the clinical picture of poisoning with mushrooms (fly agarics) containing muscarine.
Nicotine effects are manifested by convulsions, twitching of muscle fibers, contractions of individual muscle groups, general weakness and paralysis due to depolarization. On the part of the heart, both tachycardia and (more often) bradycardia can be observed.
The central effects of OP poisoning are dizziness, agitation, confusion, hypotension, respiratory depression, and coma. Death usually occurs due to respiratory failure.
What to do? What measures should be taken and in what order? According to WHO recommendations, “treatment should be started immediately.” At the same time, assistance measures must be complete and comprehensive.
First of all, FOS should be removed from the injection site. FOS should be washed off the skin and mucous membranes with a 3-5% solution of SODIUM HYDROCARBONATE or simply with soap and water. In case of intoxication due to ingestion of substances, it is necessary to lavage the stomach, prescribe adsorbents and laxatives, and use high siphon enemas. These events are carried out repeatedly. If FOS enters the blood, its excretion in the urine is accelerated (forced diuresis). The use of hemosorption, hemodialysis and peritoneal dialysis is effective.
The most important component of the treatment of acute OP poisoning is drug therapy. If overexcitation of M-cholinergic receptors is observed during FOS poisoning, then it is logical to use antagonists - M-cholinergic blockers. First of all, ATROPINE should be administered intravenously in large doses (10-20-30 ml in total). Doses of atropine are increased depending on the degree of intoxication. The airway is monitored and, if necessary, intubation and artificial respiration are performed. Guidelines for additional administration of atropine are the state of breathing, convulsive reaction, blood pressure, pulse rate, salivation (salivation). The administration of atropine at a dose of several hundred milligrams per day is described in the literature. In this case, the pulse rate should not exceed 120 beats per minute.
In addition, in case of FOS poisoning, it is necessary to use specific antidotes - acetylcholinesterase reactivators. The latter include a number of compounds containing an OXYME group (-NOH) in the molecule: dipyroxime - a quaternary amine, as well as isonitrosine - a tertiary amine; (amp., 15% - 1 ml). The reaction follows the scheme: AChE - P = NOH. Dipiroxime interacts with FOS residues associated with acetylcholinesterase, releasing the enzyme. The phosphorus atom in AChE compounds is tightly bound, but the P = NOH bond, that is, phosphorus with the oxime group, is even stronger. In this way, the enzyme is released and restores its physiological activity. But the action of cholinesterase reactivators does not develop quickly enough, so it is most advisable to use AChE reactivators together with M-anticholinergic blockers. Dipyroxine is prescribed parenterally (1-3 ml subcutaneously and only in particularly severe cases intravenously).
M-cholinomimetics have a direct stimulating effect on Mcholinergic receptors. The standard for such substances is the alkaloid muscarine, which has a selective effect on M-cholinergic receptors. Muscarine is not a medicine, and the poison contained in fly agaric mushrooms can cause acute poisoning.
Muscarine poisoning produces the same clinical picture and pharmacological effects as AChE agents. There is only one difference - here the effect on M-receptors is direct. The same basic symptoms are noted: diarrhea, difficulty breathing, abdominal pain, salivation, constriction of the pupil (miosis - the circular muscle of the pupil contracts), decreased intraocular pressure, a spasm of accommodation (near point of vision), confusion, convulsions, coma.
Of the M-cholinomimetics, the most widely used in medical practice are: PILOCARINA HYDROCHLORIDE (Pilocarpini hydrochloridum) powder; eye drops 1-2% solution in bottles of 5 and 10 ml, eye ointment - 1% and 2%, eye films containing 2.7 mg of pilocarpine), ACECLIDINE (Aceclidinum) - amp. - 1 and 2 ml of 0.2% solution; 3% and 5% - eye ointment.
Pilocarpine is an alkaloid from the shrub Pilocarpus microphyllus, (South America). Currently obtained synthetically. Has a direct M-cholinomimetic effect.
By stimulating effector organs that receive cholinergic innervation, M-cholinomimetics cause effects similar to those observed when irritating autonomic colinergic nerves. Pilocarpine especially strongly increases the secretion of glands. But pilocarpine, being a very strong and toxic drug, is used only in ophthalmic practice for glaucoma. In addition, pilocarpine is used for thrombosis of retinal vessels. Use topically, in the form of eye drops (1-2% solution) and eye ointment (1 and 2%) and in the form of eye films. It constricts the pupil (3 to 24 hours) and reduces intraocular pressure. In addition, it causes a spasm of accommodation. The main difference from AChE agents is that pilocarpine has a direct effect on M-cholinergic receptors of the eye muscles, and AChE agents have an indirect effect.
ACECLIDINE (Aceclidinum) is a synthetic direct-acting M-cholinomimetic. Less toxic. They are used for local and resorptive action, that is, they are used both in ophthalmic practice and for general effects. Aceclidine is prescribed for glaucoma (slightly irritates the conjunctiva), as well as for atomy of the gastrointestinal tract (in the postoperative period), bladder and uterus. When administered parenterally, there may be side effects: diarrhea, sweating, salivation. Contraindications: bronchial asthma, pregnancy, atherosclerosis.
DRUGS THAT BLOCK M-CHOLINORECEPTORS (M-CHOLINORECEPTORS, ATROPINE-LIKE DRUGS)
M-CHOLINOBLOCKERS OR M-CHOLINOLYTICS, DRUGS OF THE ATROPINE GROUP - these are drugs that block M-cholinergic receptors. A typical and most well-studied representative of this group is ATROPINE - hence the group is called atropine-like drugs. M-cholinergic blockers block peripheral Mcholinergic receptors located on the membrane of effector cells at the endings of postganglionic cholinergic fibers, that is, they block PARASYMPATHIC, cholinergic innervation. By blocking the predominantly muscarinic effects of acetylcholine, the effect of atropine on the autonomic ganglia and neuromuscular synapses does not extend.
Most atropine-like drugs block M-cholinergic receptors in the central nervous system.
An M-anticholinergic blocker with high selectivity of action is ATROPINE (Atropini sulfas; tablets 0.0005; ampoules 0.1% - 1 ml; 1% eye ointment).
ATROPINE is an alkaloid found in plants of the nightshade family. Atropine and related alkaloids are found in a number of plants:
Belladonna (Atropa belladonna);
Belene (Hyoscyamus niger);
Datura stramonium.
Atropine is currently obtained synthetically, that is, chemically. The name Atropa Belladonna is paradoxical, since the term "Atropos" means "three fates leading to an inglorious end of life", and "Belladonna" means "charming woman" (donna is a woman, Bella is a female name in Romance languages). This term is due to the fact that the extract from this plant, instilled into the eyes of the beauties of the Venetian court, gave them a “shine” - dilated the pupils.
The mechanism of action of atropine and other drugs in this group is that by blocking M-cholinergic receptors, competing with acetylcholine, they prevent the mediator from interacting with them.
The drugs do not affect the synthesis, release and hydrolysis of acetylcholine. Acetylcholine is released, but does not interact with receptors, since atropine has a greater affinity (affinity) for the receptor. Atropine, like all M-cholinergic blockers, reduces or eliminates the effects of irritation of cholinergic (parasympathetic) nerves and the effect of substances with M-cholinomimetic activity (acetylcholine and its analogues, AChE agents, M-cholinomimetics). In particular, atropine reduces the effects of irritation n. vagus The antagonism between acetylcholine and atropine is competitive, therefore, when the concentration of acetylcholine increases, the effect of atropine at the point of application of muscarine is eliminated.
MAIN PHARMACOLOGICAL EFFECTS OF ATROPINE
1. Atropine has especially pronounced antispasmodic properties. By blocking M-cholinergic receptors, atropine eliminates the stimulating effect of parasympathetic nerves on smooth muscle organs. The tone of the muscles of the gastrointestinal tract, bile ducts and gallbladder, bronchi, ureters, and bladder decreases.
2. Atropine also affects the tone of the eye muscles. Let's look at the effects of atropine on the eye:
a) when atropine is administered, especially when applied topically, due to a block of M-cholinergic receptors in the circular muscle of the iris, pupil dilation is noted - mydriasis. Mydriasis also intensifies as a result of the preservation of the sympathetic innervation of m. dilatator pupillae. Therefore, atropine acts on the eye for a long time in this regard - up to 7 days;
b) under the influence of atropine, the ciliary muscle loses its tone, it becomes flattened, which is accompanied by tension in the ligament of Zinn, which supports the lens. As a result, the lens also flattens, and the focal length of such a lens lengthens. The lens sets vision to the far point of vision, so nearby objects are not clearly perceived by the patient. Since the sphincter is in a state of paralysis, it is not able to constrict the pupil when viewing nearby objects, and photophobia (photophobia) occurs in bright light. This condition is called ACCOMMODATION PARALYSIS or CYCLOPLEGIA. Thus, atropine is both a mydriatic and a cycloplegic. Local application of a 1% atropine solution causes a maximum mydriatic effect within 30-40 minutes, and complete restoration of function occurs on average after 3-4 days (sometimes up to 7-10 days). Paralysis of accommodation occurs within 1-3 hours and lasts up to 8-12 days (approximately 7 days);
c) relaxation of the ciliary muscle and displacement of the lens into the anterior chamber of the eye is accompanied by a violation of the outflow of intraocular fluid from the anterior chamber. In this regard, atropine either does not change intraocular pressure in healthy individuals, or in individuals with a shallow anterior chamber and in patients with narrow-angle glaucoma, it may even increase, that is, lead to an exacerbation of an attack of glaucoma.
INDICATIONS FOR THE USE OF ATROPINE IN OPHTHALMOLOGY
1) In ophthalmology, atropine is used as a mydriatic to cause cycloplegia (paralysis of accommodation). Mydriasis is necessary when examining the fundus of the eye and in the treatment of patients with iritis, iridocyclitis and keratitis. In the latter case, atropine is used as an immobilization agent that promotes functional rest of the eye.
2) To determine the true refractive power of the lens when selecting glasses.
3) Atropine is the drug of choice if it is necessary to achieve maximum cycloplegia (paralysis of accommodation), for example, when correcting accommodative strabismus.
3. INFLUENCE OF ATROPINE ON ORGANS WITH SMOOTH MUSCLE. Atropine reduces the tone and motor activity (peristalsis) of all parts of the gastrointestinal tract. Atropine also reduces peristalsis of the ureters and the bottom of the bladder. In addition, atropine relaxes the smooth muscles of the bronchi and bronchioles. In relation to the biliary tract, the antispasmodic effect of atropine is weak. It should be emphasized that the antispasmodic effect of atropine is especially pronounced against the background of a previous spasm. Thus, atropine has an antispasmodic effect, that is, atropine acts in this case as an antispasmodic. And only in this sense can atropine act as a “painkiller”.
4. INFLUENCE OF ATROPINE ON THE ENDOCRECTION GLANDS. Atropine sharply weakens the secretion of all exocrine glands, with the exception of mammary glands. In this case, atropine blocks the secretion of liquid watery saliva caused by stimulation of the parasympathetic part of the autonomic nervous system, causing dry mouth. Tear production decreases. Atropine reduces the volume and overall acidity of gastric juice. In this case, suppression and weakening of the secretion of these glands can be up to their complete shutdown. Atropine reduces the secretory function of glands in the cavities of the nose, mouth, pharynx and bronchi. The secretion of the bronchial glands becomes viscous. Atropine, even in small doses, inhibits the secretion of SWEAT GLANDS.
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M- and N-CHOLINOMIMETICS
Direct acting M- and N-cholinomimetics
M-, N-cholinomimetics include drugs that excite both M- and N-cholinergic receptors. Based on their effect on cholinergic receptors, M- and N-cholinomimetics can be divided into substances of direct and indirect action (anticholinesterase agents). Direct-acting drugs themselves cause excitation of M- and N-cholinergic receptors. Direct-acting M-, N-cholinomimetics include acetylcholine, which excites M- and N-cholinergic receptors and causes a number of changes in the body associated with the predominance of excitation of M-cholinergic receptors: vasodilation, decreasedblood pressure, slowing of heart contractions, increased contractions of smooth muscles of internal organs, increased secretion of glands, constriction of the pupil. Since acetylcholine is quickly destroyed by the enzyme cholinesterase, its effect is short-lived, so it is rarely used for therapeutic purposes (for spasms of peripheral vessels, narrowing of the retinal arteries, etc.). Acetylcholine chloride is used in medical practice.
ACETYLCHOLINE CHLORIDE . Release form acetylcholine chloride: 0.2 g of dry matter in ampoules with a capacity of 5 ml. List B.
Example of a recipe for acetylcholine chloride in Latin:
Rp.: Acetylcholini chloridi 0.2
D.t. d. N. 10 in ampull.
S. Dissolve in 2-5 ml of water for injection, inject subcutaneously or intramuscularly.
M-, N-CHOLINOMIMETICS OF INDIRECT ACTION (ANTICHOLINESTERASE DRUGS)
These drugs block the action of cholinesterase, an enzyme that destroys acetylcholine, resulting in the accumulation of acetylcholine, which has a long-term effect on M- and H-cholinergic receptors. There are reversible anticholinesterase agents that temporarily inactivate the cholinesterase enzyme: physostigmine, proserine, oxazil, galantamine, etc. A few hours after the administration of these drugs, cholinesterase activity is completely restored. Another group of substances - anticholinesterase agents of irreversible action: paraxon, armin, etc. - causes a longer blockade of cholinesterase; they are more toxic. This group also includes some insecticides (chlorophos, karbofos, etc.) and toxic substances. Anticholinesterase drugs are used to treat glaucoma (M-cholinomimetic effect), eliminate postoperative atony of the intestines and bladder (M-cholinomimetic effect), myasthenia gravis, residual effects of poliomyelitis, disorders of neuromuscular transmission (N-cholinomimetic effect), and are also used in case of overdose muscle relaxants with antidepolarizing action (N-cholinomimetic effect). Side effects of anticholinesterase drugs: bradycardia, decreased blood pressure, increased secretion of glands, increased tone of skeletal muscles, nausea, vomiting. Contraindications to the use of anticholinesterase drugs: epilepsy, bronchial asthma, organic heart disease.
PHYSOSTIGMINE SALICYLATE - used mainly in ophthalmic practice for glaucoma (lowers intraocular pressure), a combination of solutions of physostigmine salicylate (0.25%) and pilocarpine hydrochloride (1%) gives a good therapeutic effect. Physostigmine salicylate is used in the form of eye drops, 0.25-1% solution. List A.
Example of a recipe for physostigmine salicylate in Latin:
Rp.: Sol. Physostigmini salicylatis 1% 5 ml
M. D. in vitro nigro
S. Eye drops, l-2 drops 3-4 times a day.
Rp.: Pilocarpini hydrochloridi 0.1
Physostigmini salicylatis 0.025
Aq. destill. 10 ml
M. D. in vitro nigro
S. Eye drops. 1-2 drops 4-6 times a day.
PROZERIN(pharmacological analogues: neostigmine) - used for myasthenia gravis, paralysis, paresis, residual effects of poliomyelitis, glaucoma, intestinal atony, bladder. Prozerin is used as an antagonist of muscle relaxants of a competitive (antidepolarizing) type of action. Side effects of prozerin and contraindications for use are characteristic of this entire group of drugs. Prozerin release form: powder; tablets 0.015 g; ampoules of 1 ml of 0.05% solution; granules 60 g per package. List A.
An example of a proserine recipe in Latin:
Rp.: Sol. Proserini 0.5% 5 ml
D.S. Eye drops.
Rp.: Tab. Proserini 0.015 N. 20
D.S. 1 tablet 2 times a day.
Rp.: Sol. Proserini 0.05% 1 ml
D.t. d. N. 10 in ampull.
S. 0.5-1 ml subcutaneously 1-2 times a day.
Cholinomimetics
Cholinomimetics- see Cholinomimetic drugs.
M-cholinomimetics- see M-cholinomimetic drugs.
N-cholinomimetics- see N-cholinomimetic drugs.
Cholinomimetic agents
Cholinomimetic agents - I
drugs that reproduce the effects of stimulation of cholinergic receptors by their natural ligand - acetylcholine. The cholinergic effect can be enhanced both by direct interaction of Ch. with a certain type of cholinergic receptor (direct-acting cholinergic), and the preservation of excess acetylcholine in the synapse by inhibiting cholinesterase that destroys it (indirect-acting cholinergic). In the second case, excitation of all types of cholinergic receptors is initiated, incl. localized in the central nervous system and at neuromuscular junctions of skeletal muscles. H. s. indirect action form an independent group of anticholinesterase drugs (Anticholinesterase drugs).
H. s. direct action in accordance with the classification of cholinergic receptors (see Receptors) are divided into m-, n- and n+m-cholinomimetics.
m-cholinomimetics- aceclidine and pilocarpine - cause local (when applied topically) or general effects of stimulation of m-cholinergic receptors: miosis, accommodation spasm, decrease in intraocular pressure; bradycardia, slowing of atrioventricular conduction; bronchospasm, increased tone and motility of the gastrointestinal tract, bladder, uterus; secretion of liquid saliva, increased secretion of bronchial, gastric and other exocrine glands. All these effects are prevented or eliminated by the use of atropine and other m-cholinergic drugs (see Anticholinergic drugs), which are always used in cases of overdose of m-cholinomimetics, poisoning with substances with a similar or anticholinesterase effect.
Indications for the use of m-cholinomimetics: glaucoma, thrombosis of the central retinal vein; atony of the stomach, intestines, bladder, uterus, postpartum uterine bleeding. General contraindications to their use are bronchial asthma, angina pectoris, myocardial damage, intra-atrial and atrioventricular blockade, gastrointestinal bleeding, peritonitis (before surgery), hyperkinesis, epilepsy, normal pregnancy.
Aceclidine- powder (for the preparation of eye drops in the form of 2%, 3% and 5% aqueous solutions) and 0.2% solution in ampoules of 1 and 2 ml for subcutaneous injections. For glaucoma, instillation into the eye is carried out from 2 to 6 times a day. In case of acute atony of the bladder, 1-2 ml of 0.2% solution is administered subcutaneously; in the absence of the expected result, the injections are repeated 2-3 times with an interval of half an hour, unless undesirable effects are expressed (hypersalivation, bronchospasm, bradycardia, etc.).
Pilocarpine hydrochloride used mainly in ophthalmological practice. Its main forms of release: 1% and 2% solutions in bottles of 5 and 10 ml; 1% solution in dropper tubes; 1% solution with methylcellulose in bottles of 5 and 10 ml; eye films (2.7 mg of pilocarpine hydrochloride each); 1% and 2% eye ointment. Most often, 1% and 2% solutions are used, instilling them into the eye 2 to 4 times a day.
n-cholinomimetics- alkaloids lobeline and cytisine - excite postsynaptic cholinergic receptors in the ganglia of the sympathetic and parasympathetic nervous system, in the carotid glomeruli and in the chromaffin tissue of the adrenal glands (increased adrenaline secretion). As a result, both adrenergic and cholinergic influences on the executive organs are activated. At the same time, the action of cytisine (the drug Cititon) is dominated by adrenergic peripheral effects (increased blood pressure, increased heart contractions), while the action of lobeline is dominated by cholinergic effects (bradycardia, decreased blood pressure are possible). Both alkaloids reflexively (from the receptors of the carotid reflex zone) excite the respiratory center and are used mainly as respiratory analeptics in cases of acute respiratory arrest (against the background of long-term depression of the respiratory center, the effect is unstable). Their nicotine-like effect became a prerequisite for the use of lobeline (Lobesil tablets) and cytisine (Tabex films and tablets) to facilitate smoking cessation. Their use for this purpose is contraindicated in case of organic diseases of the cardiovascular system, persistent arterial hypertension, angina pectoris, gastric and duodenal ulcers, bleeding.
Lobeline hydrochloride- 1% solution in ampoules of 1 ml; tablets 2 mg (drug "Lobesil"). In case of acute respiratory arrest in adults, 0.3-0.5 ml (for children 0.1-0.3 ml depending on age) is administered intramuscularly or intravenously slowly (over 1-2 minutes), because rapid administration threatens collapse and cardiac arrest. In case of overdose, vomiting, convulsions, severe bradycardia, and profound respiratory depression are also possible. During the period of quitting smoking, Lobesil is prescribed in the first week, 1 tablet up to 5 times a day, then the frequency of doses is reduced until withdrawal (20-30 days). In case of poor tolerability (dizziness, weakness, nausea), the drug is discontinued.
Cititon- 0.15% cytisine solution in ampoules of 1 ml; Tabex tablets and films for cheek (or gum) application, 1.5 mg each. Due to its pressor effect, it is used more often than lobeline, because acute respiratory depression often occurs against the background of collapse or shock. Adults are administered intravenously or intramuscularly 0.5-1 ml (children under 1 year - 0.1 ml). For those who quit smoking, the general scheme for using Tabex tablets is the same as Lobesil tablets; The films are changed 4-8 times in the first three days, then 3 times a day, from the 13th to the 15th day 1 film is used, then discarded.
n+m-cholinomimetics are represented by acetylcholine (a drug), which is practically not used in medical practice, and carbacholine, which is similar in chemical structure.
Carbacholine is not destroyed by cholinesterase and has a longer lasting and more pronounced cholinergic effect than acetylcholine. The overall effect is dominated by the effects of excitation of m-cholinergic receptors, and only against the background of their blockade do n-cholinergic effects clearly appear. At the same time, carbocholine has no advantages over drugs from the m-cholinomimetics group, therefore, of the previously known forms of its release, only eye drops (in the form of 0.75%, 1.5%, 2.25% and 3% p -carbacholine) for the treatment of glaucoma. During eye surgeries, sometimes 0.5 ml of 0.01% carbacholine solution is injected into the anterior chamber of the eye to narrow the pupil.
cholinergic drugs with different mechanisms of action, causing effects characteristic of excitation of cholinergic receptors.
M-cholinomimetic drugs(syn.: M-cholinomimetics, M-cholinergic drugs) - X. s., stimulating or promoting the excitation of M-cholinergic receptors (pilocarpine, aceclidine, etc.)
N-cholinomimetic drugs(syn.: H-cholinomimetics, H-cholinergic drugs) - X. s., stimulating or promoting the excitation of H-cholinergic receptors (lobeline, cytisine, etc.).
Encyclopedic Dictionary of Medical Terms M. SE-1982-84, PMP: BRE-94, MME: ME.91-96.
Effects of M-cholinomimetics (=excitation of M-cholinergic receptors):
Effect on the eyes. Excitation of M-cholinergic receptors of the circular muscle of the iris leads to its contraction, and the pupil narrows (miosis). Constriction of the pupil and flattening of the iris helps to open the angles of the anterior chamber of the eye and improve the outflow of intraocular fluid, which reduces intraocular pressure. M-cholinomimetics increase the curvature of the lens, causing a spasm of accommodation. The eye is set to near vision (myopia). Side effect “Disturbance of accommodation”
Effect on the exocrine glands. The secretion of saliva increases, as well as lacrimation and sweating
Effect on the bronchi: stimulate contraction of the circulatory muscles of the bronchi (tone increases to bronchospasm), mucus secretion in the bronchi increases.
Effect on the heart: slow down the heart rate (bradycardia), inhibit the conduction of impulses along
conduction system of the heart.
Effect on the gastrointestinal tract: increase the secretion of the glands of the gastrointestinal tract, increase peristalsis, and the tone of the sphincters of the digestive tract (and bladder), on the contrary, decreases.
Effect on the bladder: increased tone bladder, possible urinary incontinence
Indications for the use of M-cholinomimetics:
1) glaucoma, to reduce intraocular pressure (symptomatic therapy).
2) When atony of the intestines and bladder: drugs increase tone while simultaneously relaxing the sphincters, increasing contraction (peristalsis) of these smooth muscle organs, facilitating their emptying.
Clinical picture of poisoning M-cholinomimetics, as well as fly agaric mushroom(contains muscarine)
severe bradycardia, bronchospasm, painful increased peristalsis (diarrhea), sudden sweating, salivation, constriction of the pupils and spasm of accommodation occur, and convulsions are possible. All these symptoms are eliminated
M-cholinergic blockers (atropine and others are antidotes).
Pilocarpine(Pilocarpinum). Synonyms: Pilokarpinum hydrochloridum
Pharmaceutical group: M-cholinomimetic
Mechanism of action: Pilocarpine excites peripheral m-cholinergic receptors, causes constriction of the pupil, reduces intraocular pressure and improves trophism of eye tissue. When instilled into the conjunctival sac of the eye, it is poorly absorbed in normal concentrations and does not have a pronounced systemic effect. When taken orally, pilocarpine is quickly absorbed, but it does not exist per os. are prescribed.
Indications for use: - glaucoma!!!
To improve the trophism of the eye in case of thrombosis of the central retinal vein, acute obstruction of the retinal artery, with atrophy of the optic nerve, with hemorrhages into the vitreous body.
To stop the mydriatic effect after using atropine, homatropine, scopolamine or other anticholinergic substances to dilate the pupil during ophthalmological examinations.
Side effects:
Headache (in the temporal or periorbital areas), pain in the eye area; myopia; decreased vision, especially in the dark, due to the development of persistent miosis and spasm of accommodation; lacrimation, rhinorrhea, superficial keratitis; allergic reactions. With prolonged use, the development of conjunctivitis and eyelid dermatitis is possible; when using systems with prolonged release of the drug - the development of tolerance
Contraindications:
Hypersensitivity, iritis, cyclitis, iridocyclitis, keratitis, condition after ophthalmological operations and other eye diseases in which constriction of the pupil is undesirable. Caution in patients with a history of retinal detachment and in young patients with high myopia.
Release forms: 1% solutions in bottles of 5 and 10 ml; 1% solution in dropper tubes of 1.5 ml; Now there is no -1% and 2% eye ointment; eye films
Drugs that stimulate H-cholinergic receptors (H-cholinomimetics)
Effects:
1) reflex excitation of the respiratory center of the medulla oblongata through activation of cholinergic receptors of the sinocarotid zone
2) increase blood pressure due to stimulation of cells of the adrenal medulla and sympathetic ganglia (the release of adrenaline and norepinephrine increases).
3) facilitate the conduction of impulses to skeletal muscles (in case of overdose - convulsions)
N-cholinomimetics penetrate well into the central nervous system, especially lobeline, and can cause bradycardia and a decrease in blood pressure (activation of the vagal center), vomiting (excitation of the vomiting center), convulsions (excitation of cells of the anterior central gyrus and anterior horns of the spinal cord).
Indications for use of AChE agents:
1) in case of respiratory arrest associated with carbon monoxide poisoning, drowning, brain injury, electrical injury, or inhalation of irritating substances. They are effective only if the reflex excitability of the respiratory center is maintained.
2) to facilitate smoking cessation.
Cytisine (Cytisinum) is an alkaloid found in the seeds of the Russian broom and Thermopsis lanceolifolia plants, both from the legume family. As a respiratory analeptic, it is available in the form of a 0.15% solution called “Cytitonum” in 1 ml ampoules. As a means of quitting smoking - in the form of Tabex tablets.
Cititon. Mechanism of action: excites H-cholinergic receptors in the carotid zone, which reflexively leads to excitation of the respiratory center. Simultaneous stimulation of the sympathetic nodes and adrenal glands leads to an increase in blood pressure.
The effect of cititon (cytisine solution) on breathing is of a short-term “push-like” nature, but in some cases, especially with reflex stops of breathing, the use of cititon can lead to a permanent restoration of breathing and blood circulation.
It is used for reflex cessation of breathing (during operations, injuries, etc.) It has a pressor effect (which distinguishes it from lobeline). Therefore, cititon can be used in shock and collaptoid conditions, in respiratory and circulatory depression in patients with infectious diseases, etc. Cititon is administered intravenously or intramuscularly.
Cititon is contraindicated (due to its ability to increase blood pressure) in cases of severe atherosclerosis and hypertension, bleeding from large vessels, and pulmonary edema.
"Tabex"- tablets to ease smoking cessation. Mechanism of action: excites the same H-cholinergic receptors as nicotine. Reduces the need for the number of cigarettes smoked, facilitates temporary abstinence from smoking, and alleviates withdrawal symptoms that occur when quitting smoking completely.
Drugs that stimulate M and H cholinergic receptors
Cholinomimetics are drugs that increase excitation in the area of cholinergic nerve endings.
Classification
They are divided into direct cholinomimetics, which cause stimulation of cholinergic receptors, and indirect anticholinesterase elements, which inactivate cholinesterase. The direct type is usually further divided into M- and N-cholinomimetics in pharmacology.
M-cholinomimetics are able to excite predominantly central interneuron synapses or peripheral neuro-effector areas of executive organs. They contain M-cholinergic receptors. These include Pilocarpine and Aceclidine.
H-cholinomimetics are drugs that cause stimulation of H-cholinergic receptors. They are considered innervated neurons. At the same time, their bodies are located in the central and, in addition, in the sympathetic and parasympathetic nodes. They are also found in the adrenal medulla and in the carotid glomerulus. These include the drugs “Cititon” along with “Lobeline”. M- and N-cholinomimetics that excite cholinergic receptors include Carbacholine.
We will consider the use of cholinomimetics in this article.
Operating principle
Anticholinesterase drugs block absolutely all active catalytic regions of acetylcholinesterase. Such processes lead to the accumulation of acetylcholine in the area of the synaptic cleft. As part of the classification of processes according to the mechanism of influence, they are divided into groups such as irreversible and reversible influence.
When a direct type of cholinomimetics is administered in the body, the effects associated with the excitation of parasympathetic nerves can significantly predominate. For example, this will be expressed in the form of a slowdown in heart rate, a decrease in the intensity of heart contractions.
Changes
In addition, the following changes occur:
- Intraocular pressure decreases.
- Spasms of accommodation occur.
- The pupils narrow.
- Intestinal motility increases.
- The tone of all internal organs increases, especially the condition of smooth muscles improves.
- Urination increases.
- Vessels dilate.
- There is a decrease in blood pressure along with relaxation of the sphincters.
Thus, they are agents that accelerate the mechanism of action of cholinergic nerves.
Cholinomimetics are substances that imitate the effects of acetylcholine and have an effect on the functioning of a particular organ similar to irritation of cholinergic nerves. Some cholinomimetic agents, for example nicotinomimetic substances, may act primarily on nicotine-sensitive cholinergic receptors. These include the following components: nicotine, anabasine, lobelia, cytisine and subecholine. As for muscarine-sensitive cholinergic receptors, substances such as muscarine, arecoline, pilocarpine, benzamon, aceclidine and carbacholine act on them. The effects of cholinomimetics are unique.
Their mechanism of action is identical to the mechanism of acetylcholine, which is released in the endings of cholinergic nerves. It can also be introduced externally. Like acetylcholine, these drugs have a positively charged nitrogen atom in their molecule.
Let us consider in more detail the mechanism of action of cholinomimetics for each type.
N-cholinomimetics
N-cholinomimetics are substances that excite n-cholinergic receptors. Such elements are also called nicotine-sensitive receptors. N-cholinergic receptors are associated with channels of cell membranes. When H-cholinergic receptors are excited, the channels open and membrane depolarization occurs, which causes an energetic effect. Cholinomimetics have been used in pharmacology for a long time.
H-cholinergic receptors predominate in the neurons of the parasympathetic and sympathetic ganglia, as well as in the chromaffin cells of the adrenal medulla and in the area of the carotid tangles. In addition, H-cholinergic receptors can be found in the central nervous system, especially in cells that have an inhibitory effect on motor neurons in the spinal cord.
N-cholinergic receptors are localized in neuromuscular synapses, that is, in the area of the end plates of skeletal muscles. If they are stimulated, contraction of skeletal structures may occur.
M-cholinomimetics
We will consider the drugs below. M-cholinomimetic substances can enhance the secretion of sweat, digestive, and bronchial glands. In addition, due to their effects, the following reactions of the body are observed:
It is worth noting that M-cholinomimetic drugs are used primarily for the treatment of glaucoma. The constriction of the pupils, which is caused by these components, leads to a decrease in intraocular pressure. What is the mechanism of cholinomimetics?
The effects of substances that excite M- and N-cholinergic receptors are mainly similar to the effects of M-cholinomimetic drugs. This is accomplished due to the stimulation of H-cholinergic receptors. Among the substances that belong to the M- and N-cholinomimetics, only anticholinesterase drugs are widely used.
The mechanism of action of M-cholinomimetics is of interest to many.
Drug poisoning
Poisoning with these drugs may be accompanied by the following body reactions:
- There is a sharp increase in the secretion of saliva, as well as sweat.
- Diarrhea.
- Constriction of the pupils.
- Slowing heart rate. It should be noted that in case of poisoning with anticholinesterase drugs, the pulse, on the contrary, increases.
- Fall in blood pressure.
- Asthmatic breathing.
Treatment of poisoning in this situation should be limited to administering Atropine or other anticholinergic drugs to the patient.
Application
Cholinomimetics are substances that excite cholinergic receptors. They are typically used in ophthalmic medicine as a miotic agent that can lower intraocular pressure. Within this framework, tertiary amines, which are well absorbed by the conjunctiva, are preferentially used, especially drugs such as Pilocarpine and Aceclidine.
How to explain the constriction of the pupils
Constriction of the pupils under the influence of M-cholinomimetics can be explained by contraction of the orbicularis muscles of the iris, which receives the cholinergic innervation provided to it. This orbicularis muscle contains M-cholinergic receptors. In parallel, due to the process of contraction of the ciliary muscle, which has a similar innervation, spasms of accommodation occur, that is, an adjustment to the curvature of the lens for near vision.
Decreased intraocular pressure
Along with pupil constriction, M-cholinomimetics, as part of their effect on the eye, can cause another very important clinical effect, namely, a decrease in intraocular pressure. It is this process that is used to treat glaucoma.
This effect can be explained by the fact that during the constriction of the pupil, the iris thickens, due to which the lymphatic slits located in the corner of the anterior chamber of the visual organ widen. Due to this, there is an increase in the outflow of fluid from the inner regions of the eye, which, in fact, causes a decrease in intraocular pressure. True, such a mechanism is not considered the only reason for the decrease in intraocular pressure caused by M-cholinomimetics, due to the fact that there is no strict correlation between the miotic effects they provoke and the decrease in intraocular pressure.
Miotic effect
The miotic effect of M-cholinomimetics, when alternating them with mydriatic drugs, can also be used to break adhesions that interfere with the regulation of pupil width. The resorptive effect of substances that excite M-cholinergic receptors is used for intestinal and bladder atony.
In order to avoid the wasteful process of excitation of the ganglia, it is preferable to selectively use active M-cholinomimetics, such as Mecholin or Bethanechol. They are administered subcutaneously to ensure rapid action as well as dosage accuracy. Considering that this route is not associated with absorption through the mucosa, solutions of quaternary amines, including Carbacholin, Mecholin or Bethanechol, are injected subcutaneously. The effect of cholinomimetics has not been fully studied.
Components that block cholinergic receptors and their use
Substances that block M-cholinergic receptors have wider therapeutic applications compared to M-cholinomimetics. In the clinic of diseases of the visual organs, selectively influencing M-anticholinergics are used to dilate the pupils, which causes relaxation of the circular muscles of the iris. They are also used for a temporary nature, during which the ciliary muscles relax. Most often, a solution of “Atropine” in the form of eye drops is used for such purposes. Cholinomimetic drugs are presented below.
Relaxation of the circular and ciliary muscles of the iris creates complete peace of the intraocular state, which is used for inflammatory processes, and also for eye injuries. The dilation of the pupils caused by M-anticholinergics, along with paralysis of accommodation, is also used as part of the study of refractive error. For these purposes, instead of Atropine, they prefer to use short-acting M-anticholinergics, usually they are drugs such as Amizil, Homatropin, Euphthalmin and "Metamisil." Their solutions are prescribed in the form of eye drops.
Where is Atropine used?
The main purpose for the resorptive use of selective M-anticholinergics is spasms of smooth muscle organs. Such organs are the stomach, intestines, bile ducts, and the like. For this, “Atropine” is used directly, as well as plants that contain it, for example, belladonna and others. In addition, numerous synthetic M-anticholinergics may be suitable.
An important reason for the use of M-anticholinergics is their central effect. Selective M-anticholinergics with central action include drugs such as Amizil, Benzacin, Metamizil and other amino alcohol esters, which contain tertiary nitrogen along with aromatic acids, including hydroxyl. As part of blocking central M-cholinergic receptors, they potentiate the effect of sleeping pills, as well as narcotic and analgesic drugs, preventing overexcitation of the hypothalamic centers, which manage the pituitary-adrenal system.
Conclusion
Thus, cholinomimetic drugs are substances that can excite cholinergic receptors, that is, the biochemical systems of the body. They cannot be homogeneous. They are selectively sensitive to nicotine and are located in the ganglia of the sympathetic and, in addition, parasympathetic nerves. They can also be observed in the adrenal medulla along with carotid tangles and in the endings of the motor elements of the central nervous system. Cholinergic receptors may also exhibit selective sensitivity to the alkaloid muscarine.
We reviewed the classification of cholinomimetics.
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