M cholinomimetics characteristic development history. Cholinomimetics. Classification. M-cholinomimetics and N-cholinomimetics. Mechanism of action. pharmacological effects. Application. Side effects. Influence on the structures of the eye

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M- and N-cholinomimetics of direct action. This group of drugs mimics the effects of the endogenous mediator acetylcholine. Acetylcholine chloride is of limited use because it is rapidly degraded by cholinesterase. It is prescribed in the muscle or under the skin with spasm of peripheral vessels (spasm of the arteries of the retina, endarteritis, trophic disorders in the stumps, etc.). When injected into a vein, the drug causes cardiac arrest and a drop in blood pressure (collapse). The drug is contraindicated in bronchial asthma, atherosclerosis, epilepsy, angina pectoris.

Carbacholine has a longer duration of action (it is not destroyed by cholinesterase). In addition to direct action on receptors, the drug causes stimulation of the release of ACh. Carbacholin is used for postoperative atony of the intestines and bladder, with obliterating endarteritis, with glaucoma (in the form of eye drops). Contraindications and possible complications of carbachol are the same as those of acetylcholine chloride.

M- and N-cholinomimetics of indirect action. The mechanism of action of this group of drugs is associated with the inactivation of cholinesterase, which leads to the accumulation of endogenous ACh, enhancing its effect on organs and tissues. In addition, anticholinesterase agents have a direct effect on cholinergic receptors. Cholinesterase inhibition can be reversible (this is how, in particular, prozerin acts). In this case, the effect of the drugs is short-lived. In the formation of covalent bonds of the drug with the enzyme, its irreversible inhibition (phosphorylation) occurs, while the effect of the drug is long. Anticholinesterase drugs of the tertiary structure easily penetrate the BBB, restore the conduction of impulses in the central nervous system, including increasing the activity of the respiratory center, so they can be used in case of poisoning with substances that depress the central nervous system, with residual effects after poliomyelitis, and with cerebral palsy. Quaternary compounds (prozerin) do not penetrate into the central nervous system, therefore they have a predominantly peripheral effect. Indications for use: residual effects after poliomyelitis, cerebral hemorrhage, myasthenia gravis, glaucoma, atony of the intestines, bladder, uterus, as antagonists of antidepolarizing muscle relaxants.

Preparations irreversible action(Armin) due to its high toxicity, it is used only for glaucoma in the form of eye drops. Complications: hypersalivation, bradycardia, miosis, diarrhea, frequent urination, twitching of the muscles of the tongue and skeletal muscles.

Contraindicated anticholinesterase drugs with a tendency to convulsions, bronchial asthma, angina pectoris, severe atherosclerosis, pregnancy.

M-cholinomimetics (M-XM)

M-cholinomimetics stimulate M-ChR of various localizations like acetylcholine.

Influence on the cardiovascular system. Cardiac branches of the vagus innervate mainly the sinus node of the heart (the myocardium is not supplied with parasympathetic fibers), under the influence of M-XM, the frequency of generation of impulses of the sinus node decreases. Bradycardia develops, blood pressure and minute volume decrease. This leads to a decrease in myocardial oxygen demand with an increase in the utilization of glucose and organic acids. There is also a decrease in the conductivity and automatism of the heart.

Mechanisms for the development of hypotension:

1. Slowdown of the heart;

2. Stimulation of M-XR vessels of skeletal muscles, which leads to their expansion;

3. Stimulation of M-XR sweat glands, which, through a series of chemical reactions, causes an increased formation of bradykinin (an endogenous vasodilator);

4. Expansion of the vessels of the brain, heart, genital organs.

Influence on the bronchi. M-XM significantly increase the tone of the bronchi, increase the secretion of the bronchial glands, which can cause an asthma attack.

Action on the gastrointestinal tract. Under the influence of M-cholinomimetics, the motility of the gastrointestinal tract (especially the small intestine) and the secretion of the gastric and intestinal glands, including the pancreas, increase. The sphincters of the alimentary canal relax. The rate of evacuation of food masses increases, intestinal atony and constipation are eliminated. Therefore, drugs of this group are used for postoperative intestinal atony.

Action on salivary and sweat glands. The secretion of the salivary glands increases, which can be used in dentistry (1% solution of pilocarpine hydrochloride in drops inside). Due to the strong diaphoretic effect of M-XM (up to 10-14 liters of sweat per day), it is sometimes used in acute renal failure, when it is not possible to use a hemodialysis machine.

Influence on the structures of the eye.

1. Constriction of the pupil is the result of stimulation of M=XR of the circular muscle of the iris.

2. Decrease in intraocular pressure - contraction of the circular muscles leads to the opening of the corner of the eye (iris root), which leads to the expansion of the fountain spaces located at the base of the root, and an increase in the outflow of fluid through them into the canal of Schlemm and the venous sinus of the sclera.

3. Spasm of accommodation - the result of contraction of the ciliary muscle due to stimulation of M-ChR in it. This leads to relaxation of the ligament of zon, which is attached to the belly of the muscle. In this case, the lens, due to its elasticity, becomes more convex, and vision is set to near vision.

4. Lachrymation is the result of M-XR stimulation of the lacrimal glands.

Action on the CNS. M-XM, stimulating the corresponding receptors of subcortical and stem formations, can cause hyperkinesias like parkinsonism, especially with a tendency to convulsions.

Testimony for the use of M-XM are: glaucoma (eye drops, ointment, films), atony of the intestines and bladder, hypotension of the uterus.

Contraindicated drugs for bronchial asthma, bradyarrhythmias, pregnancy, a tendency to convulsions, severe organic heart disease.

Cholinomimetics I Cholinomimetic agents (cholino [Receptors] + Greek mimētikos, imitating, reproducing; synonyms:)

drugs that reproduce the effects of stimulation of cholinergic receptors by their natural ligand - acetylcholine. The cholinergic effect can be enhanced as a direct interaction of H. with. with a cholinergic receptor of a certain type (H. with direct action), and with the preservation of an excess of acetylcholine in the synapse by inhibiting its destroying (H. with. indirect action). In the second case, all types of cholinergic receptors are initiated, incl. localized in the c.n.s. and at neuromuscular junctions of skeletal muscles. H. s. indirect action form an independent group of anticholinesterase agents (anticholinesterase agents).

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- aceclidin and pilocarpine - cause local (when applied topically) or general effects of excitation of m-cholinergic receptors: accommodation spasm, decrease in intraocular pressure; , slowing atrioventricular conduction; , increased tone and motility of the gastrointestinal tract, bladder, uterus; 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-anticholinergics (see anticholinergic agents), which are always used in case of an overdose of m-cholinomimetics, poisoning with substances with a similar or anticholinesterase effect.

Indications for the use of m-cholinomimetics: thrombosis of the central retinal vein; stomach, intestines, bladder, uterus, postpartum. General contraindications to their use are angina pectoris, myocardial damage, intra-atrial and atrioventricular, gastrointestinal bleeding, (before surgery), epilepsy, normally proceeding.

Aceclidine- (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. With glaucoma, instillations are made 2 to 6 times a day. In acute atony of the bladder, 1-2 ml 0.2% solution; in the absence of the expected result, the injections are repeated 2-3 times with an interval of half an hour, if undesirable effects are not expressed (, bronchospasm, bradycardia, etc.).

Pilocarpine hydrochloride mainly used in ophthalmic practice. Its main forms of release: 1% and 2% solutions in vials of 5 and 10 ml; 1% solution in dropper tubes; 1% solution with methylcellulose in vials of 5 and 10 ml; eye films (2.7 mg pilocarpine hydrochloride each); 1% and 2% ophthalmic. Most often, 1% and 2% solutions are used, instilled into the eye from 2 to 4 times a day.

n-cholinomimetics- lobelin and cytisine - excite postsynaptic in the ganglia of the sympathetic and parasympathetic nervous system, in the carotid glomeruli and in the chromaffin tissue of the adrenal glands (increased secretion of adrenaline). As a result, both adrenergic and cholinergic influences on the executive organs are activated. At the same time, adrenergic peripheral effects (increase, increased heart contractions) predominate in the action of cytisine (cytiton), and cholinergic effects (possible bradycardia, lowering blood pressure) in the action of lobelin. Both alkaloids reflexively (from the receptors of the carotid reflex zone) excite the respiratory and are used mainly as respiratory in cases of acute respiratory arrest (against the background of prolonged depression of the respiratory center, the effect is unstable). Their nicotine-like action has become a prerequisite for the use of lobelin (Lobesil tablets) and cytisine (Tabex films and tablets) to facilitate smoking cessation. Their use for this purpose is contraindicated in organic diseases of the cardiovascular system, persistent arterial hypertension, angina pectoris, peptic ulcer of the stomach and duodenum, bleeding.

Lobeline hydrochloride- 1% solution in ampoules of 1 ml; tablets 2 mg(drug "Lobesil"). In acute respiratory arrest in adults, 0.3-0.5 ml(children 0.1-0.3 ml depending on age) intramuscularly or intravenously slowly (for 1-2 min), because rapid introduction threatens with collapse and cardiac arrest. In case of an overdose, convulsions, severe bradycardia, and deep respiratory depression are also possible. Lobesil in the period of weaning from smoking is prescribed in the first week, 1 tablet up to 5 times a day, then the frequency of intake is reduced until it is canceled (20-30 days). With poor tolerance (, weakness,), the drug is canceled.

Cititon- 0.15% solution of cytisine in ampoules of 1 ml; Tabex tablets and films for buccal (or gum) applications 1.5 each mg. In connection with the pressor action, it is used more often than lobelin, because. acute respiratory depression often occurs against the background of collapse, shock. Adults intravenously or intramuscularly administered 0.5-1 ml(children up to 1 G ode - 0.1 each ml). For those who quit smoking, the general scheme for using Tabex tablets is the same as for Lobesil tablets; 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 canceled.

n+m-cholinomimetics are represented by acetylcholine (a drug), which is practically not used in medical practice, and carbacholine, which is close to it in chemical structure.

carbacholin is not destroyed by cholinesterase and has a longer lasting and more pronounced cholinergic effect. In the total action, the effects of excitation of m-cholinergic receptors predominate, and only against the background of their blockade, n-cholinergic effects are clearly manifested. At the same time, carbocholine has no advantages over drugs of the m-cholinomimetics group, therefore, of the previously known forms of its release, only ophthalmic ones have been left and are practically used (in the form of 0.75%, 1.5%, 2.25% and 3% p- moat of carbachol) for the treatment of glaucoma. During eye operations, sometimes 0.5 ml 0.01% solution of carbachol.

1. Small medical encyclopedia. - M.: Medical Encyclopedia. 1991-96 2. First aid. - M.: Great Russian Encyclopedia. 1994 3. Encyclopedic dictionary of medical terms. - M.: Soviet Encyclopedia. - 1982-1984.

See what "cholinomimetic agents" are in other dictionaries:

Medicinal substances, the action of which is similar to the effect of excitation of cholinergic receptors of the biochemical systems of the body, with which acetylcholine reacts (for example, pilocarpine) ... Big Encyclopedic Dictionary

Pharmacological substances of various chemical structures, the action of which basically coincides with the effects of excitation of cholinergic nerve fibers (See Cholinergic nerve fibers) or the mediator Acetylcholine. By ... ... - (cholinomimetica; choline + Greek mimetikos capable of imitating, imitating; synonym: cholinomimetics, cholinergic drugs) cholinergic drugs with a different mechanism of action, causing effects characteristic of arousal ... ... Big Medical Dictionary

CHOLINOMIMETIC DRUGS- cholinomimetics, drugs. substances that act like acetylcholine on the cholinergic systems of synapses. According to the ability to act on muscarino or nicotine-sensitive synapses X. s. subdivided into m cholinomimetics (arecoline hydrobromide ... Veterinary Encyclopedic Dictionary

- (syn.: M cholinomimetics, M anticholinergics) X. s., stimulating or stimulating the excitation of M cholinergic receptors (pilocarpine, aceclidin, etc.) ... Big Medical Dictionary

- (syn.: N cholinomimetics, N anticholinergics) X. s., stimulating or facilitating the excitation of N cholinergic receptors (lobelia, cytisine, etc.) ... Big Medical Dictionary

Anticholinergics, pharmacological substances that block the transmission of excitation from cholinergic nerve fibers (See Cholinergic nerve fibers), acetylcholine mediator antagonists. They belong to different groups... Great Soviet Encyclopedia

- (anticholinergic, anticholinergic, anticholinergics), lek. in va, warning, weakening and stopping the interaction. neurotransmitter acetylcholine and cholinomimetic. funds with cholinergic receptors. Due to the presence in the central and peripheral ... ... Chemical Encyclopedia

Preparations of this group carry out an exciting effect on various types of cholinergic receptors.

Pharmacomarketing

Classification and preparations

Depending on what type of cholinergic receptors the action is manifested, all cholinomimetics are divided into:

M-cholinomimetics;

N-cholinomimetics;

M-N-cholinomimetics;

Rice. fourteen

mechanism of action

Cholinergic receptors - these are genetically determined mobile lipoprotein, protein or glycoprotein molecules. Cholinergic receptors are constantly destroyed and re-synthesized. The duration of the existence of the cholinergic receptor is about seven days. In addition to the two main types, muscarinic and nicotine, there are several subtypes. Intracellular mediators (messengers) in the formation of the reaction to the excitation of the cholinergic receptor are cGMP, Ca 2+ , Na + , K + . They are closely associated with adenylate cyclase, calcium, sodium or potassium channels.

M-hopinomimetics excite M-cholinergic receptors; H hopinomimetics - N-cholinergic receptors, while M-N-hapinomimetics excite both M and H-cholinergic receptors. In the contractile mechanism of smooth muscle fibers during excitation of cholinergic receptors, the activation of bound intracellular Ca 2+, membrane guanylate cyclase and an increase in the amount of intracellular mediator - cyclic 3,5 guanosine monophosphate (cGMP) play a role.

Rice. fifteen

The cholinergic receptor acts by increasing the concentration of cGMP (cyclic guanidine monophosphate).

When the cholinergic receptor is excited, it binds to the G protein, which consists of 3 subunits (α, β, γ).

The α-subunit is released, which activates guanylate cyclase (GC). HC breaks down guanidine triphosphate (GTP) into cGMP.

Pharmacological

Rice. 16

When they are introduced into the body, the effect associated with the excitation of parasympathetic nerves prevails. Of greatest practical interest is the effect of M-chodinomimetics on the eye. Due to their local action on the eye, they reduce intraocular pressure, cause miosis and spasm of accommodation. (Fig. I).

The mechanism of these changes is the excitation of hopioreceptors and the contraction of the internal muscles of the eye, which receive parasympathetic innervation. So, due to the contraction of the iris muscle, the pupil narrows (miosis). The outflow of fluid from the anterior chamber is improved due to the opening of the fountains of space, which underlies the iris and scutum canal.

Rice. 17

The internal pressure of the eye is reduced strongly and for a long time. The contraction of the ciliary muscle of the eye is accompanied by its thickening and the movement of the belly of the muscle (to which the Qing connection is attached) closer to the lens. Due to the relaxation of the Qing connection, the lens capsule does not stretch, and due to its elasticity, it acquires a more convex shape. The eye is set to close vision (spasm of accommodation).

As a result of the resorptive action of cholinomimetics, bronchospasm, bradycardia (there may even be cardiac arrest), an increase in the tone of the undisturbed muscles of the gastrointestinal tract, uterus, gallbladder and bladder, increase the secretion of the salivary, bronchial, gastrointestinal and sweat glands.

Acetylcholine also has a metabolic function as a local hormone, for example, in non-innervated structures of the placenta and in ciliary epithelial cells.

In this way, M-cholinomimetics increase the tone of the intestines, muscles of the bladder, uterus, bronchi, reduce intraocular pressure, dilate peripheral vessels.

N-cholinomimetics reflexively stimulate the respiratory center. There is tachycardia and arterial hypertension as signs of excitation by acetylcholine of H-cholinergic receptors of sympathetic nodes, chromaffin cells of the adrenal medulla and chemoreceptors of the carotid glomerulus.

Indications for use and interchangeability

In glaucoma, carbacholine and all M-cholinomimetics (local action) are used.

With atony of the intestines, bladder, M-N-cholinomimetics, acecpidin are taken.

With reflex respiratory arrest, N-hopinomimetics are used.

With weakness of labor, aceclidine is prescribed.

With endarteritis, acetylcholine is sometimes used.

For X-ray diagnostics of diseases of the stomach, intestines, aceclidin, acetylcholine are used.

Side effect

At high doses of cholinomimetics, bradycardia, a decrease in blood pressure, increased salivation, and bronchospasm can be observed.

When using carbacholin, thirst, salivation, and nausea sometimes appear.

With the introduction aceclidine solution into the conjunctival sac may cause slight irritation of the conjunctiva.

Contraindications

M-cholinomimetics are contraindicated in bronchial asthma, severe heart disease, pregnancy, epilepsy, hyperkinesis.

Pharmacosecurity

Cholinomimetics are incompatible with antiparkinsonian, anticonvulsant, antidepressants, antiarrhythmics, antipsychotics, antihistamines, β-adrenergic blockers, glucocorticosteroids, aminoglycosis, idama, local anesthetics.

Acetylcholine is incompatible with mezaton.

Introduction to the vein acetylcholine is impossible because there may be a sharp decrease in blood pressure and cardiac arrest.

Comparative characteristics of drugs

M-N-hodynomshetics

Acetylcholine is not stable and is rapidly absorbed in tissues due to the action of cholinesterase. Its rapid destruction is of great physiological importance, since this ensures the flexibility of the nervous regulation of organ functions.

As a drug, acetylcholine is not widely used. When taken orally, the drug is ineffective due to the fact that it is rapidly hydrolyzed by acetylcholinesterase. When administered parenterally, it gives a quick, sharp, but short-lived effect. Like other quaternary compounds, acetylcholine does not penetrate well through the blood-brain barrier and does not have a significant effect on the central nervous system. Acetylcholine is sometimes used as a vasodilator for spasms of peripheral vessels.

carbacholin in terms of chemical structure and pharmacological properties, it is close to acetylcholine, but is more active and exhibits a longer effect, since it is not hydrolyzed by cholinesterase. The stability of the drug allows it to be used not only for parenteral administration, but also for oral administration.

M-cholinomimetics

Pilocarpine - an alkaloid derived from Pilocarpus laborandi, which grows in Brazil. Only local action is used - for glaucoma.

Aceclidine stimulates predominantly M-cholinergic receptors of the intestine, bladder, uterus. Miosis and a decrease in intraocular pressure are more pronounced than after the administration of pilocarpine. In surgical and obstetric-gynecological practice, it is used to prevent and eliminate postoperative atony of the muscles of the gastrointestinal tract and bladder, with a decrease in the tone and subinvolution of the uterus, to stop hemorrhages in the postpartum period. Aceclidine is a valuable pharmacological agent for X-ray examination of the esophagus, stomach and duodenum.

N-chalinamimetics

lobelin and cytiton according to the mechanism of action, they belong to this group, and according to pharmacodynamics, they belong to reflex respiratory analeptics.

Only their ability to excite H cholinergic receptors of the carotid sinuses and thus reflexively stimulate the respiratory center is not used. Their gimulyuvalny effect is very strong, but short-lived (2-5 minutes when administered intravenously). The main indications for the use of lobelin and cytiton are carbon monoxide poisoning, morphine, and neonatal asphyxia.

list of drugs

Classification: M-HMPolocarpine hydrochloride, Aceclidine

N-HM Respiratory analeptics: Lobeline hydrochloride, Cititon

For the treatment of nicotine addiction: Anabasine chloride, Tabex

M and H-XMAcetylcholine, Carbacholin

Mechanism d-I: Cholinergic agents are structurally or spatially similar to the ACh molecule to varying degrees. Therefore, they can interact either with cholinergic receptors, or with parts of the cell membrane surrounding them, or with enzymes (mainly with cholinergic receptors).

M-cholinomimetics: They stimulate M-cholinergic receptors. They imitate irritation of parasympathetic nerves. Effect on the heart: the work of the heart slows down, cholinergic receptors of the vessels of the skeletal muscles (vasodilation) are excited, the secretion of the muscle relaxant factor by vascular endothelial cells, this leads to hypotension, a decrease in heart rate to a stop. Slow conduction to A-B block. With intravenous administration of M-hm, sudden cardiac arrest is possible. Effect on the gastrointestinal tract: Increase the tone and excite intestinal motility, at the same time relax the sphincters of the digestive canal. Eliminates intestinal atony. Effect on the bladder: Increased tone and contractile activity of the muscles of the bladder. Sphincter relaxation. Effect on eyes: Cause constriction of the pupils (miosis). Reduce intraocular pressure. They cause a spasm of accommodation. Contraction of the circular muscle of the eye (ciliary) is accompanied by thickening of the muscle and moving the place where the zinn ligament is attached closer to the lens. The lens takes on a more convex shape. The eye is set for near vision. For bronchi: Spasm For glands: Increased secretion. For the gallbladder: Increase in tone.

Indications: 1. Glaucoma. Pilocarpine hydrochloride. 2-4 times a day 1-5% solution of a drop, ointment. Eye films at night for the lower eyelid. The action of aceclidine is shorter.

2. Atony and paresis of the intestines and bladder. Apply aceclidin. Fewer side effects. Subcutaneously, 1-2 ml of a 0.2% solution, if necessary - repeatedly

In 30 minutes.

Contraindications: Bronchospasm, lowering blood pressure, severe heart disease, pregnancy, epilepsy. These effects are prevented or reversed by atropine.

N-cholinomimetics: Biphasic action on H-cholinergic receptors: 1st - excitation 2nd - depression

Breathing stimulants: Are entered only intravenously. effects:

Able to excite the chemoreceptors of blood vessels, as a result of which -1. Stimulation of respiration of the reflex type. The effect is strong, but short-lived (2-5 minutes with intravenous administration). With intravenous administration, minimal doses are needed to activate the respiratory center. with subcutaneous or IM - the dosage is increased by 10-20 times. With these methods of administration, they penetrate well into the central nervous system, cause vomiting, convulsions, activation of the vagal center with possible cardiac arrest. 2. Stimulation of cardiovascular activity. Application: limited. With shock, asphyxia of newborns. With respiratory arrest (injury) With collaptoid conditions. With infectious diseases with respiratory depression and hematopoiesis. Contraindications: Hypertension, bleeding, pulmonary edema. COMPARATIVE Preparations: CITITON. This is a 0.15% solution of the alkaloid cytisine. Reflex excites respiration. At the same time, it increases blood pressure, which distinguishes it from lobelin.

CYTIZINE is part of the Tabex tablets, which facilitate smoking cessation. LOBELINA HYDROCHLORIDE. Excites the center of the vagus nerve, which leads to a decrease in blood pressure.

For beaming nicot. dependencies: According to the scheme, with a gradual decrease in dose. ANABAZIN - tablets inside or under the tongue, buccal films, chewing gum. TABEX - (contains cytisine alkaloid) LOBESIL - contains lobelia alkaloid)

NICORETTE - (contains nicotine) inhaler in the form of a mouthpiece, taking into account the behavioral aspects of addiction, chewing gum, patch, nasal spray, mini-pill. It takes 3 months to completely stop smoking with a gradual decrease in the dose.

M,N-cholinomimetics: The fact of activation of M-cholinergic receptors predominates. ACETYLCHOLINE chloride. Rarely used. Inside is ineffective.

It is administered subcutaneously and intramuscularly - a quick, sharp, short-term effect. Intravenously it is impossible because of a sharp decrease in blood pressure and cardiac arrest.

Application: With spasms of peripheral vessels (endarteritis). With spasms of the arteries of the retina. CARBACHOLINE. More active. Lasts longer. Inside, subcutaneously, intramuscularly, intravenously (with caution). Application: Endarteritis.

Locally in the form of eye drops for glaucoma.

Cholinomimetics

In cholinergic synapses (parasympathetic nerves, preganglionic sympathetic fibers, ganglia, all somatic), excitation is transmitted by the mediator acetylcholine. Acetylcholine is formed from choline and acetylchoenzyme A in the cytoplasm of cholinergic nerve endings.

Cholinergic receptors, excited by acetylcholine, have unequal sensitivity to certain pharmacological agents.

This is the basis for the selection of the so-called: 1) muscarinic-sensitive and 2) nicotine-sensitive cholinergic receptors, that is, M- and H-cholinergic receptors.

M-cholinergic receptors are located in the postsynaptic membrane of cells of effector organs 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 sympathetic and parasympathetic ganglia), the adrenal medulla, the carotid sinus zone, the end plates of skeletal muscles and the central nervous system (in the neurohypophysis, Renshaw cells, etc.). The sensitivity to pharmacological substances of different H-cholinergic receptors is not the same, which allows you to isolate the H-cholinergic receptors of ganglia and H-cholinergic receptors of skeletal muscles.

Classification of drugs that affect cholinergic receptors

M-cholinomimetics have a direct stimulating effect on Mholinoceptors. The standard of such substances is the alkaloid muscarine, which has a selective effect on M-cholinergic receptors. Muscarine is not a cure, but the poison contained in the fly agaric can cause acute poisoning.

1. M-cholinomimetics:

Poisoning with M-cholinomimetics (including fly agarics):

Complaints of the patient: blurred vision, weakness, sweating, salivation, abdominal pain, vomiting, diarrhea, shortness of breath. On examination: the pupils are constricted, the skin is moist, the pulse is rare (bradycardia - less than 60 beats per minute), blood pressure is lowered, bronchospasm, delirium, hallucinations.

Help:

I. Prevent absorption of poison into the body.

Rinse the stomach with potassium permanganate to clean washings.

In the last funnel - activated carbon (20-30g suspension)

3. Cleanse the intestines: cleansing enema or saline laxatives (Mg SO 4 - 25g per glass of water inside).

II. Poison inactivation: IV antidote-atropine 0.1% - 1 ml. repeatedly.

III. Remove poison from the body (purify the blood)

1. The method of forced diuresis - intravenous drip of 0.9% Na Cl, 5% glucose solution up to 1.5-2 liters. with diuretic furosemide

2. Hemodialysis - removal of poison using the apparatus "artificial kidney"

3. Hemosorption - removal of poison from the blood using columns with coal.

4. Peritoneal dialysis - removal of poisons by flushing the abdominal cavity with dialysis solutions.

5. Plasmapheresis - replacement of blood plasma containing toxic substances.

IV. Symptomatic treatment: bronchodilators, antispasmodics, etc.

Rep: Sol. Pilocarpini bydrochloridi 1% -10 ml.

D.S. Instill 2 drops in both eyes 2 times a day

N-cholinomimetics:

There is a similar drug LOBELIN The action is exactly the same as that of the cytiton, but somewhat weaker than the latter.

Use the drug to stimulate breathing.

Introduced in / in (only, because the action is reflex)

Side effects: in case of overdose, excitation of the vomiting center, cardiac arrest, respiratory depression, convulsions.

Contraindications: severe damage to the cardiovascular system, respiratory arrest when the respiratory center is depleted.

Rp: Cytitoni I ml.

D.t.d.N 10 in ampull.

S. Into a vein0.5 ml. in 10 ml. physical solution.

Slowly !

Rep: Sol. Lobelini hydrochloridi 1% -1 ml.

D.t.d.N 10 in ampull.

S. In a vein, 0.5 ml. in 10 ml. physical solution.

Slowly!

Lecture #17

Lecture topic: M, N-cholinomimetics. Anticholinesterase agents.

M-, N-cholinomimetics

Means that directly stimulate M- and N-cholinergic receptors (M-, N-cholinomimetics) include acetylcholine and its analogues (carbacholine).

Acetylcholine, is a mediator in cholinergic synapses, is an ester of choline and acetic acid and belongs to monoquaternary ammonium compounds.

As a drug, it is practically not used, since it acts sharply, quickly, almost instantly, very briefly (minutes).

When taken orally, it is ineffective, as it is hydrolyzed. In the form of chloride, acetylcholine 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 (in / in the introduction is unacceptable, since the blood pressure drops sharply), M-cholinomimetic effects predominate: bradycardia, vasodilation, increased tone and contractile activity of the muscles of the bronchi, gastrointestinal tract.

Acetylchline causes a stimulating effect on the H-cholinergic receptors of skeletal muscles.

Anticholinesterase agents.

Anticholinesterase agents (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 synapse region, that is, in the region of cholinergic receptors.

Under the influence of anticholinesterase agents, the rate of destruction of acetylcholine slows down, which exhibits a longer effect on H-cholinergic receptors. This is the main mechanism of action of anticholinesterase agents.

Based on the stability of the interaction of anticholinesterase drugs with acetylcholinesterase, they are divided into 2 groups:

1) AChE means of reversible action. Their action lasts 2-10 hours. These include: physostigmine, prozerin, galantamine and others.

2) AChE means of an irreversible type of action. These agents bind very strongly 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 remedy for the group of reversibly acting AChE agents is

PHYSOSTIGMIN (it was used for a long time as a weapon and as a means of justice, since according to belief, only a truly guilty person dies from poison), which is a natural alkaloid from Calabar beans, that is, the dried mature seeds of the West African climbing tree Physotigma venenosum.

PROZERIN which, like other drugs of this group (galanthamine, etc.), is a synthetic compound

. Prozerin chemical structure is a simplified analogue of physostigmine containing a quaternary ammonium group. This distinguishes it from physostigmine. In connection with the unidirectional action of all the listed drugs, they will have almost common effects.

Indications: myasthenia gravis, paresis, paralysis, glaucoma, atony of the intestines, stomach, bladder, as an antagonist of muscle relaxants.

The effect of a single dose of prozerin appears after 10 minutes and lasts up to 3-4 hours.

Increased intestinal tone (up to diarrhea),

Bradycardia

Bronchospasm (especially in persons prone to this

P p: epilepsy, bronchial asthma, organic heart disease.

GALANTAMIN - Caucasian snowdrop alkaloid - has almost the same indications for use as prozerin. Due to the fact that it penetrates the BBB better (a tertiary amine, and not a quaternary one, like proserin), it is more indicated in the treatment of residual effects after polio.

For resorptive action, prescribe (that is, action after absorption) PYRIDOSTIGMIN whose influence is longer than prozerin.

P p: epilepsy, hyperkinesia, bronchial asthma, angina pectoris, atherosclerosis, in patients with impaired swallowing and breathing.

THE SECOND GROUP OF AChE MEANS - AChE means of an "irreversible" type of action.

SIGNS OF PHOS AND AChE POISONING WITH SUBSTANCES IN GENERAL. OPC poisoning has a very characteristic clinical picture. The patient's condition is usually severe. The effects of muscarinic and nicotine type are noted. First of all, the patient is found:

1) spasm of the pupil (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 the excitation of M-cholinergic receptors (muscarinic effects) and correspond to the clinical picture of poisoning with mushrooms (fly agaric) containing muscarine.

Nicotinic effects are manifested by convulsions, twitching of muscle fibers, contractions of individual muscle groups, general weakness and paralysis due to depolarization. From the side of the heart, both tachycardia and (more often) bradycardia can be noted.

The central effects of OPC poisoning are realized by dizziness, agitation, confusion, hypotension, respiratory depression, and coma. Death usually occurs due to respiratory failure.

Help:

1. 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.

2. In case of intoxication due to ingestion of substances, it is necessary to wash the stomach, prescribe adsorbent and laxatives, use high siphon enemas. These activities are carried out repeatedly.

3. If FOS has got into the blood, it is accelerated to be excreted in the urine (forced diuresis). The use of HEMOSORPTION, hemodialysis and peritoneal dialysis is effective.

4 The most important component of the treatment of acute OPC 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, it is necessary to inject Atropine in large doses. Doses of atropine increase depending on the degree of intoxication.

In addition, in case of OPC poisoning, it is necessary to use specific antidotes - acetylcholinesterase reactivators.

dipyroxime - (amp., 15% - 1 ml). Dipiroxime interacts with FOS residues associated with acetylcholinesterase, releasing the enzyme and restoring its physiological activity.

But the action of reactivator cholinesterase does not develop quickly enough, therefore, the most appropriate use of AChE reactivators, coupled with M-cholinergic blockers. Dipyroxine is prescribed parenterally (1-3 ml s / c and only in especially severe cases / in).

Lecture #18

Lecture topic:Anticholinergics

M-anticholinergics

Poisoning Mx, lytic or plants from which they are obtained.

Complaints: blurred vision (photophobia), dry mouth, hoarseness, headache, dizziness, restlessness, palpitations.

Inspection: The pupils are dilated, the skin is red, dry, the temperature is elevated, delirium and hallucinations are possible.

Help: see poisoning M-h.m. (toadstools).

Differences: II - antidote - physostigmine. I.Y. Symptomatic treatment: aspirin.

1) at elevated temperature - antipyretic; paracetamol,

2) when excited - tranquilizers (seduxen)

3) with hallucinations - antipsychotics (chlorpromazine)

4) in case of photophobia, place in a dark room.

Ganglioblockers

Rep: Sol. Atropine sulfatis 1%-5ml

D.S. Instill 2 drops in both eyes before examining the fundus.

Rp.: Sol. Atropin sulfatis 0.1%-1ml

D.t.d. No. 10 ampull

S. Under the skin, 1 ml 2 times a day.

Rp.: Sol. Platyphyllini hydrohartratis 0.2%-1ml

D.t.d. No. 10 ampull

S. Under the skin, 1 ml as part of a triad.

Rp.: Sol. Methacini 0.1-1ml

D.t.d. No. 10 ampull

S. Under the skin, 1 ml for renal colic.

Rp.: Sol. Benzohexonii 2.5%-1ml

D.t.d. No. 10 ampull

Rp.: Sol. Pentamini 5%-1ml

D.t.d. No. 10 ampull

S. 1 ml per muscle in case of hypertensive crisis,

then lie down for 1.5-2 hours.