Cholinomimetics use. Cholinomimetics. Classification. M-cholinomimetics and N-cholinomimetics. Mechanism of action. pharmacological effects. Application. Side effects. Muscarine poisoning symptoms and relief measures

Cholinomimetics (cholinomimetics) are substances that excite cholinergic receptors - the biochemical systems of the body with which acetylcholine reacts. Cholinergic receptors are not homogeneous. Some of them show selective sensitivity to nicotine and are called nicotine-sensitive, or n-cholinergic receptors. n-cholinergic receptors are located in sympathetic and parasympathetic nerves, in the adrenal medulla, in carotid glomeruli, in the endings of motor nerves in the central nervous system. Other cholinergic receptors show selective sensitivity to muscarine, an alkaloid isolated from fly agaric. Therefore, they are called muscarinic-sensitive, or m-cholinergic receptors. m-cholinergic receptors are located at the endings of postganglionic parasympathetic (cholinergic) nerve fibers, as well as in the central nervous system.

Depending on the effect on certain cholinergic receptors, there are three groups of cholinomimetic agents: 1) n-cholinomimetic agents - substances that predominantly excite n-cholinergic receptors: lobelin (see), (see), (see); 2) m-cholinomimetic agents - substances that predominantly excite m-cholinergic receptors: aceclidin (see), benzamon (see), (see); 3) substances that excite both n- and m-cholinergic receptors: anticholinesterase agents (see), carbacholin (see).
n-cholinomimetics excite respiration and increase blood pressure. They are used primarily for emergency respiratory stimulation.

m-cholinomimetic agents increase the secretion of digestive, bronchial and; slow down the heart rate; dilate blood vessels, lower blood pressure; cause contraction of the smooth muscles of the gastrointestinal tract, bronchi, bile and urinary tract; constrict the pupil and cause accommodation. m-cholinomimetic agents are used mainly for the treatment of glaucoma. Pupil constriction caused by these substances leads to a decrease in intraocular pressure.

The effects of substances that excite m- and n-cholinergic receptors are basically similar to the effects of m-cholinomimetic agents. This is because the excitation of n-cholinergic receptors is masked by the simultaneous excitation of m-cholinergic receptors. Among the substances related to m- and n-cholinomimetics, only anticholinesterase agents find wide therapeutic use.

Poisoning with m- and n-cholinomimetic agents is characterized by a sharp increase in secretion, sweat, constriction of the pupils, slowing of the pulse (in case of poisoning with anticholinesterase drugs - increased frequency), a drop in blood pressure, and asthmatic breathing. Treatment of poisoning is reduced to the introduction of atropine (2 ml of a 0.1% solution intravenously) or others (see).

Cholinomimetics (cholinomimetics) - substances that mimic the action of acetylcholine and have the same effect on the work of the organ as irritation of the cholinergic nerves that innervate this organ.

Some cholinomimetic agents (nicotinomimetic substances) act primarily or exclusively on nicotine-sensitive cholinergic receptors. These include: nicotine, lobelia (see), cytisine, anabazine, subecholine (see).

Mostly on muscarinic cholinergic receptors act: muscarin, arecoline, aceclidin (see), benzamon (see), pilocarpine (see), carbacholin (see) - muscarinomimetic substances.

The mechanism of action of cholinomimetics is the same as the mechanism of action of acetylcholine (see), which is released in the endings of cholinergic nerves or is administered from the outside. Like acetylcholine, cholinomimetics contain a positively charged nitrogen atom in their molecule - quaternary, fully ionized (butyrylcholine, mecholyl, carbadolin, benzamon, muscarine, subecholine) or tertiary, usually highly ionized (nicotine, arecoline, aceclidin, pilocarpine, lobeline).

In addition, the cholinomimetic molecule usually contains an ester or other group that creates the same electron density distribution in the cholinomimetic molecule as in the acetylcholine molecule. Due to the similarity with acetylcholine in chemical reactivity, cholinomimetic agents interact with the same sites of activity on the surface of the cholinergic receptor with which acetylcholine reacts: positively charged nitrogen combines with the anionic site, the ether group (or a group with a similar electron distribution) - with the esterophilic site of the cholinergic receptor. The interaction of cholinomimetics with the cholinergic receptor leads to an increase in the permeability of the cell membrane for ions. The membrane depolarizes and an action potential occurs. In some organs (for example, in the heart), cholinomimetics, like acetylcholine, do not cause depolarization, but hyperpolarization. This leads to the suppression of the activity of the pacemaker of the heart, slowing the heartbeat. Unlike acetylcholine, many cholinomimetics are not destroyed by cholinesterases.

Nicotinomimetic and muscarinomimetic substances cause unequal and sometimes even opposite effects when introduced into the body. Thus, nicotinomimetic substances increase blood pressure, and muscarinomimetic substances lower it.

The action of nicotinomimetic substances consists of excitation of nicotine-sensitive cholinergic receptors of autonomic ganglia, adrenal glands, vascular reflexogenic zones (sinocarotid, etc.). The main symptoms of the action of nicotinomimetic substances when they are introduced into the body are excitation of respiration, which occurs reflexively due to excitation of the cholinergic receptors of the carotid sinus zone, and an increase in blood pressure due to increased release of adrenaline by the adrenal glands, excitation of the sympathetic ganglia, as well as a pressor reflex from the carotid glomeruli. Substances containing a secondary or tertiary nitrogen atom in the molecule (nicotine, lobelin, cytisine, anabazine) also affect the central
cholinergic receptors: cause an activation reaction on the EEG, stimulate higher nervous activity, increase the secretion of the hormone of the posterior pituitary gland. At high doses, tremors and convulsions are observed. Substances containing a quaternary nitrogen atom in the molecule (subecholine and its homologues, carbacholine) do not have a central effect, since they poorly penetrate the blood-brain barrier.

For nicotinomimetic substances, it is characteristic that when they act on cholinergic receptors, after excitation, blocking of cholinergic receptors occurs, which become insensitive to both acetylcholine and cholinomimetic agents. The exception is subecholine. It is possible that the absence of a "lytic" phase during its action is partly due to the fact that it is rapidly destroyed by cholinesterase.

Muscarinomimetic substances excite cholinergic receptors that perceive impulses from postganglionic cholinergic nerves. They reproduce the effects of excitation of the parasympathetic nervous system. They cause contraction of the circular muscles of the iris, narrowing of the pupils, a decrease in intraocular pressure, a spasm of accommodation. Enhance the secretion of glands - salivary, lacrimal, gastrointestinal tract and mucous glands of the respiratory tract. Strengthen the tone and peristalsis of the stomach and intestines; increase the tone and cause contractions of the bladder and uterus. They cause a slowing of the rhythm and a decrease in the strength of heart contractions, a shortening of the refractory period and a violation of the bundle of His; cause vasodilation, especially of the skin. Influencing the heart and blood vessels, they cause a pronounced hypotensive effect. Muscarinomimetic substances with tertiary nitrogen in the molecule (arecoline, aceclidine) also excite the central muscarinic-sensitive cholinergic receptors. At the same time, an activation reaction is observed on the EEG, the development of conditioned reflexes is accelerated; at high doses, a tremor of central origin is observed.

Some nicotinomimetic substances are used as respiratory stimulants during its reflex stop; with respiratory depression caused by an overdose of drugs during anesthesia, poisoning with barbiturates and analgesics, carbon monoxide, etc .; to enhance ventilation of the lungs in the postoperative period in order to prevent pneumonia; to combat neonatal asphyxia. As a respiratory stimulant, subecholine has advantages over lobelin and cytiton, since it is devoid of a central (side) action, is quickly destroyed by cholinesterase and does not show a second, blocking phase of action. Due to the large therapeutic breadth of action, subecholine can be administered not only intravenously, but also subcutaneously. Lobelin and cytiton can only be administered intravenously, since they are not effective in therapeutic doses when administered subcutaneously.

Muscarinomimetic substances are used in the clinic mainly for the same indications as anticholinesterase ones: as miotic agents - to reduce intraocular pressure in glaucoma and other eye diseases; to combat atony of the intestines and bladder in the postoperative period; in case of poisoning with anticholinergic substances as physiological antagonists. Cholinomimetics are usually weaker than anticholinesterase agents and not as long lasting. Carbacholine is sometimes used for paroxysmal tachycardia.

Nicotinomimetic substances are contraindicated in high blood pressure and in diseases in which an increase in pressure is undesirable (severe cardiovascular pathology, pulmonary edema, severe atherosclerosis). Muscarinomimetic substances are contraindicated in bronchial asthma, severe organic heart disease, angina pectoris, bleeding from the gastrointestinal tract, and pregnancy.

A side effect of nicotinomimetic substances is an increase in blood pressure, and in the case of the use of lobelin and cytisine, also in the central effects: nausea, dizziness may occur. Muscarinomimetic substances can cause salivation, sweating, diarrhea, reddening of the skin, pressure drop.

Poisoning with nicotinomimetic substances is manifested in increased pressure, increased respiration, palpitations; lobelin and cytisine can cause dizziness, nausea, and vomiting. In case of poisoning with subecholine (with a 50-fold increase in the therapeutic dose), respiratory arrest may occur due to paralysis of the respiratory muscles. Antagonists of nicotinomimetic substances are ganglioblocking and sympatholytic substances. Poisoning with muscarinomimetics is manifested in the excitation of the parasympathetic system: a sharp narrowing of the pupils, lacrimation, increased secretion of the glands, a slowing of the heartbeat, vasodilation, a drop in blood pressure, spasm of the smooth muscles of the bronchi, intestines, and bladder. All these phenomena are easily removed by atropine and other muscarinolytic substances.

Topic: " Cholinomimetics"
Plan:

1) The concept of M-and N-cholinergic receptors.

2) Classification of cholinomimetics.

3) Localization of M-cholinergic receptors.

4) Comparative characteristics of M-cholinomimetics.

5) Symptoms of Muscarine poisoning. First aid.

6) Localization of H-cholinergic receptors.

7) Comparative characteristics of N-cholinomimetics.

8) Comparative characteristics of M, N-cholinomimetics of direct and indirect action (anticholinesterase agents).

9) Symptoms of FOS poisoning. First aid.
All cholinergic receptors are divided into:

1.M-cholinergic receptors- muscarinic sensitive. Muscarine is the poison of fly agaric.

2.N-cholinergic receptors nicotine sensitive. Nicotine is an alkaloid from tobacco leaves.

When studies of the nervous system were carried out on animals, it was found that receptors localized in some organs are equally sensitive and respond to small doses of muscarine, bind to it, causing a change in the functions of these organs and do not respond to nicotine at all. They were called M-cholinergic receptors. Receptors in other organs are sensitive to low doses of nicotine, bind to it and cause changes in the functions of these organs, and do not respond to muscarine. They were called H-cholinergic receptors. All cholinergic receptors are divided into subtypes: M1, M2, Hn, H m. Each subtype has its own strict localization and a specific function. Drugs acting in cholinergic systems are divided into 2 groups: Cholinomimetics and Cholinergic blockers.

Classification of cholinomimetics

M-cholinomimetics: N-cholinomimetics:

Pilocarpine, Aceclidine, Cisapride. Cititon, Lobelin,

Anabasin, Tabex, Lobesil

M, N-cholinomimetics:

direct action: indirect action

Acetylcholine Anticholinesterase

Carbocholine

Indirect action (Anticholinesterase):

a) Reversible action: b) Irreversible action:

Physostigmine Armin

Galantamine FOS (organophosphorus

Prozerin (Neostigmine) compounds): Chlorophos,

Oksazil (Ambenonium) Dichlorvos

Pyridostigmine (Kalimin) Tabun, Sarin

Distigmine (Ubretide) (chemical attack agent)

M-cholinomimetics have a direct stimulating effect on M-cholinergic receptors. A typical representative is muscarine (fly agaric alkaloid).

Localization of M-cholinergic receptors:

M-cholinergic receptors localized mainly in the PS nervous system:

1). In the central nervous system (subcortical structures, reticular formation, cortex);

2) In postganglionic fibers in the heart. They are contained by the vagus nerve, which has an inhibitory effect on the heart;

3) In postganglionic P.S. fibers innervating smooth muscles: bronchi, gastrointestinal tract, eyes, urinary and biliary tract;

4) In postganglionic P.S. fibers that innervate the cells of the glands (salivary, stomach, bronchial);

5) In postganglionic S. fibers that innervate the skin.

Effects that occur in the organs when excited

M-cholinergic receptors drugs M-cholinomimetics:

On the heart:

1. When administered intravenously, M-cholinomimetics cause sudden cardiac arrest - they are not used parenterally !!!

2. Bradycardia (slow heart rate) because. the inhibitory vagal effect on the heart is enhanced (localization in the conduction system of the heart);

3. Decreased blood pressure (hypotension);

For bronchi:

1. Narrowing of the bronchi, to bronchospasm (suffocation), especially in patients with bronchial asthma. (not desired effects)

2. Increased secretion of bronchial glands.

Positive effects of practical interest:

1. Improving the motility of the intestines and urinary tract: the tone and peristalsis of the intestines increase, the sphincters relax at the same time, while the speed of movement of food masses, gases increases - intestinal atony, flatulence is eliminated, constipation occurs in case of an overdose (defecation delay).

2. Increasing the tone of the bladder - the atony of the bladder is eliminated, with an overdose, urinary retention occurs.

3. Increasing the tone of the muscles of the eyes: a) the circular muscle of the iris is reduced, as a result of which the pupil narrows (miosis); b) due to contraction of the ciliary muscle of the eye, the outflow of fluid from the anterior chamber of the eye increases through the fantan spaces (trabecuber network - located at the base of the iris) and helmets channel into the venous system of the eye, which leads to a decrease in intraocular pressure - used to treat glaucoma; c) contraction of the circular muscle of the eye (ciliary body of the eye) leads to the movement of the belly of the muscle, to which the ligament of zinn is attached closer to the lens. As a result, the ligament of zinn relaxes - the lens capsule stops stretching and the lens becomes more convex (because it is very elastic). As a result, there appears spasm of accommodation(eye is set for close vision)- distant objects are hard to see.

Glaucoma is a disease with a persistent increase in intraocular pressure and arching pain in the eye, leading to blindness. Its exacerbation (glaucoma crisis) requires emergency assistance! Eye drops are used to treat glaucoma: Pilocarpine, Aceclidine, which act for several hours: the lacrimal canal is pressed with a finger so that the solution does not drain into the nasal cavity - they are instilled into the conjunctival sac.

With an overdose of M-cholinomimetics the effects they cause are clearly manifested, as well as in case of poisoning with fly agaric or drugs of this group, the so-called cholinergic effects(they can be partly caused by drugs of different pharmacological groups):

Bradycardia, decrease in blood pressure (hypotension);

Difficulty breathing (bronchospasm);

Increased sweating, salivation, copious sputum;

Increased, painful intestinal motility, which is accompanied by vomiting, diarrhea;

The tone of the bladder increases, which leads to urinary retention;

Expansion of skin vessels;

Narrowing of the pupils - spasm of accommodation;

Distant objects are not clearly visible;

Psychomotor agitation and convulsions.

Death can occur from paralysis of the respiratory center.

All symptoms are easily removed by M-cholinergic blockers, which cause opposite effects, tk. are unilateral antagonists, for example, a solution of Atropine sulfate, injected s / c.

Indications:

Treatment of glaucoma, prescribe eye drops, films, ointments with Pilocarpine. Due to its high toxicity, it cannot be administered parenterally.

With atony of the stomach, intestines and bladder after surgery or pathological, Aceclidine is more often used in solution, injected subcutaneously. it is less toxic than Pilocarpine.

Contraindications:b bronchial asthma, heart disease - heart attacks, defects, pregnancy, epilepsy, hyperkinesis - increased tone of the smooth muscles of the internal organs.

Pilocarpine is an alkaloid derived from the Brazilian plant Pilocarpus pinnatifolius Jaborandi. Inside (per os) is not prescribed, with a / in the introduction causes cardiac arrest !!! They are used only locally, in ophthalmology: 1.) in the form of eye drops 1% aqueous solution of 1.5 ml. in a tube - a dropper and 1%, 2% solutions of 5 and 10 ml. in vials, appoint 1-2 drops, 3-4 p. per day in the conjunctival sac to lower intraocular pressure in glaucoma; to relieve mydriasis (pupil dilation) after the use of Atropine (for fundus research); in complex therapy with drops "Timol", "Proxodolol" - to reduce intraocular pressure; in combined preparations "Fotil", "Fotil-forte" ( pilocarpine + timolol) ; 1% solution of 5.10 ml with methylcellulose(prolonged action); 2) in the form of long-acting eye films, they are laid with eye tweezers behind the lower eyelid 1-2 times a day, collagen, swelling (wetted with lacrimal fluid), green. Each film contains 2.7 mg Pilocarpine. Packed in boxes of 20 pieces; eye films "Pyloren" ( pilocarpine 2.5 mg + adrenaline 1 mg) in 1 film; 3) eye ointment 1%, 2%, put with a spatula behind the lower eyelid 1-2 times a day.

Aceclidine "Glaudin", "Glaunorm" a solution of 0.2% ampoules, 1 and 2 ml each, injected s / c; powder for the preparation of eye drops. Apply with atony of the bladder, increases daily diuresis, postoperative atony of the muscles of the gastrointestinal tract, in obstetrics with a decrease in the tone of the uterus, to stop uterine bleeding in the postpartum period; for x-ray studies of the esophagus, stomach and duodenum, a solution is injected s / c 15 minutes before the study; in ophthalmology, 2% eye drops are used to narrow the pupils and lower intraocular pressure in glaucoma; to relieve mydriasis from eye drops of Homatropin - 5% solution, with mydriasis from Atropine and Scopolamine, it is ineffective.

Contraindications: bronchial asthma, heart disease, Zh.K.T. bleeding, epilepsy, pregnancy.

Cisapride "Coordinax", "Peristyle" tablets 0.005, 0.01, suspension in 1 ml ampoules. Refers to prokinetics, has a different mechanism of action: it enhances the release of Acetylcholine from presynaptic endings, especially the mesenteric plexus of the intestine. It increases the tone and peristalsis of the intestines and the tone of the esophageal sphincter, prevents the contents of the stomach from being thrown into the esophagus. Applied with paresis of the stomach, reflux esophagitis, intestinal atony, chronic constipation, to accelerate peristalsis during X-ray studies of the gastrointestinal tract.

Contraindications: gastrointestinal bleeding, pregnancy, lactation, liver and kidney dysfunction.

Symptoms of overdose and poisoning with M-cholinomimetics:

salivation, diarrhea, vomiting, sweating, pupillary constriction, decrease in blood pressure, slowing of the heart. Easy to remove H.B. - Atropine, Metacin.

N-cholinomimetics have a direct stimulating effect on H-cholinergic receptors.

N-cholinergic receptors are localized in the central nervous system, carotid glomeruli (accumulation of blood vessels at the branching site of the carotid artery), autonomic ganglia S and P S of the nervous system.

A typical representative is nicotine- Tobacco leaf alkaloid. Very toxic, 1-2 drops of pure nicotine kills a person. Tobacco was brought to Russia by Peter I from Holland. During the combustion of tobacco during smoking, in addition to nicotine, phenol, carbon monoxide, hydrocyanic acid, resins are inhaled with smoke. radioactive polonium - it is with him that the carcinogenic effect of tobacco is associated. Smoking causes a number of diseases of the cardiovascular system, lungs, stomach, and oncological diseases. The craving for smoking is associated with the pharmacological effects of nicotine: excitation of H-cholinergic receptors of the central nervous system, especially in the cerebral cortex, stimulation of the adrenal medulla with increased release of adrenaline, which also excites the centers of the brain, increases blood pressure, speeds up the pulse, which creates a feeling of increased efficiency, exacerbation attention. Excitation of H-cholinergic receptors of the autonomic ganglia leads to vasoconstriction, and the excitation of the carotid zone leads to reflex excitation of the respiratory center and reflex release of vasopressin, an antidiuretic hormone of the posterior pituitary gland, which also constricts blood vessels and retains fluid in the body. The medical significance of N-cholinomimetics is limited, only the ability to excite the chemoreceptors of the vessels of the carotid glomeruli is used and in this way reflexively stimulate the work of the respiratory center, i.e. they are reflex action analeptics. They act strongly, but briefly for 2-5 minutes with intravenous administration, which is used for inhibition of the respiratory center in case of barbiturate poisoning with morphine and its analogues (the sensitivity of its cells to CO2 decreases), then they resort to its reflex stimulation. With s / c and / m administration, for the proper effect, it is necessary to administer a dose of these drugs 10-20 times larger, and this leads to dangerous side effects, up to cardiac arrest, therefore, they are administered only in / in small doses. Indications for use: 1. For the resumption of breathing in case of poisoning with barbiturates, opioid analgesics, carbon monoxide, reflex cessation of breathing during operations, drowning, injuries. Apply intravenous solutions of lobelin or cytisine. Cititon an aqueous solution of the alkaloid cytisine, from the seeds of the broom plant Cytisus laburnum, 0.15%, 1 ml. lobelin 1% to 1 ml solution of alkaloid from the plant Lobelia inflate. 2. To quit smoking, apply: " Tabex, Lobesil, "Anabazin" tablets orally or sublingually according to the scheme, gradually reducing the dose, films with cytisine, 10 and 50 pieces, buccally on the gum or on the mucous membrane behind the cheek; chewing gums Gamibazin", containing anabasine, Nicorette" containing therapeutic doses of nicotine, a course of 20-25 days; Tabex tablets containing the alkaloid cytisine; Anabasin- tablets, films, chewing gum containing an alkaloid of the plant Anabasis aphilla; "Lobesil" tablets containing 0.002 mg lobeline alkaloid. Side effects: nausea, vomiting, weakness, increased blood pressure, irritability. Contraindications: peptic ulcer of the stomach and duodenum, organic diseases of the cardiovascular system, treatment should be carried out under medical supervision.

M, N-cholinomimetics of direct action.

Carbocholine, Acetylcholine. For use in medical practice and for the production of synthetic Acetylcholine chloride 0.1, 0.2 powder in vials of 5 ml. It is diluted with water for injection and injected intramuscularly, s / c. As a medicine, it is rarely used, when taken orally, it is quickly destroyed (hydrolyzed), when administered parenterally, it acts quickly, but not for long, poorly penetrates through the BBB, and does not have a central effect. It is used as a vasodilator for spasms of peripheral vessels and arteries of the retina, rarely for atony of the intestines and bladder, for x-ray studies of the esophagus. Do not inject intravenously, it can cause a sharp drop in blood pressure and cardiac arrest. Contraindications: bronchial asthma, angina pectoris, atherosclerosis, epilepsy. In case of overdose, there is a sharp decrease in blood pressure, bradycardia, profuse sweat, miosis (pupil constriction), increased intestinal motility, etc. In such cases, 1 ml is injected s / c or / in a 0.1% solution atropine.

Carbocholine powder for the manufacture of 0.5-1% ex tempore eye drops for glaucoma. Myostat - 0.01% solution, used to narrow the pupil during eye operations, is injected into the anterior chamber of the eye. B more active and longer acting than acetylcholine. It does not break down when taken orally, therefore it was produced in tablets and injection solutions, which are currently excluded from the State Register. Stronger than Acetylcholine increases the tone of the bladder and intestines, when applied topically in the form of eye drops, it reduces intraocular pressure in glaucoma.

Contraindications and side effects as in Acetylcholine.

M, N-cholinomimetics of indirect action or Anticholinesterase agents. They inhibit true and false cholinesterase, an enzyme that destroys Acetylcholine, as a result of which the mediator accumulates in the cholinergic synapse, its action is enhanced and prolonged. At the same time, both M- and H-cholinergic receptors are simultaneously excited. In addition, the anticholinesterase agents themselves, in addition to destroying the enzyme, excite cholinergic receptors, and most drugs excite M-cholinergic receptors to a greater extent, therefore, there is a decrease in heart rate, an increase in bronchial tone, miosis (narrowing) of the pupils, salivation - increased secretion of salivary, sweat, bronchial, gastric glands, increased tone and peristalsis of the intestines, bladder and biliary tract. A smaller number of drugs show more N-cholinomimetic effects: CNS excitation, vasoconstriction and increased blood pressure.

Anticholinesterase reversible action. Cholinesterase is bound for several hours, after which it is completely restored and the effect of Acetylcholine is reduced. They are most often used in medical practice:

Physostigmine and Galantamine penetrate well through the BBB, so they are prescribed for lesions (inhibition) of the central nervous system, after trauma, stroke, poliomyelitis.

Physostigmine alkaloid Calabar bean seeds of the West African plant Physostigma venenosum. F.w.: powder for the preparation of eye drops 0.25% -1% solution , in glaucoma reduces intraocular pressure when pilocarpine is not effective. For treatment b. Alzheimer's (impaired subject memory), with progressive dementia, is used in combination with nootropic drugs.

Galantamine alkaloid of tubers of Voronov's snowdrop Calanthus Woronovi and in other species of snowdrop . Release form: 0.1%, 0.25%, 0.5% and 1% solutions in ampoules of 1 ml, s / c , with residual effects after poliomyelitis, stroke, CNS injuries, to accelerate and facilitate cholinergic transmission in the perifocal zones of persistent inhibition.

Anticholinesterase irreversible action.

Irreversibly block cholinesterase, excluding cholinergic control of body functions. Not used in medicine. With the exception of the drug Armin", eye drops, 0.01% solution for the treatment of glaucoma.

FOS (organophosphorus) chlorophos, dichlorvos highly effective household insecticides. FOV (organophosphorus poisonous substances), means of chemical attack Tabun, Zarin, currently their development and use is prohibited by the International Convention.

Picture of FOS (irreversible anticholinesterase) poisoning: miosis, salivation of glands, difficulty breathing to bronchospasm, inhibition of the central nervous system is replaced by convulsive attacks, hypotension, spastic contractions of the gastrointestinal tract, vomiting, diarrhea, abdominal pain, death occurs from acute respiratory failure. First aid: the introduction of M-anticholinergics, for example, a solution Atropine sulfate s / c, or cholinesterase reactivators " Dipiroksime", "Isonitrozin".
Control questions for consolidation:
1. How were M- and H-cholinergic receptors isolated?

2. What are the symptoms of fly agaric poisoning? What are the measures of assistance?

3. What are the symptoms of chlorophos poisoning? What are the measures of assistance?

4. What plants contain substances of cholinomimetic action?

5. In what combination preparations is Pilocarpine hydrochloride used?

6. Why can solutions of Lobelin and Cytiton be administered to the body only intravenously?
Recommended literature:
Mandatory:

1. V.M. Vinogradov, E.B. Katkova, E.A. Mukhin "Pharmacology with a prescription", a textbook for pharmaceutical schools and colleges / edited by V.M. Vinogradova-4 ed.corr.- St. Petersburg: Spec. Lit., 2008-864s.: ill.
Additional:

1. M.D. Gaevyj, P.A. Galenko - Yaroshevsky, V.I. Petrov, L.M. Gaeva "Pharmacology with the formulation": Textbook. - Rostov n / a: Publishing Center "Mart", 2008 - 480s.

2.M.D. Mashkovsky "Medications" - 16th ed., Revised. Corrected. And add.-M.: New wave: Publisher Umerenkov, 2010.- 1216 p.

3. Handbook VIDAL, Medicines in Russia: Handbook. M.: AstraPharmService, 2008 - 1520s.

4. Atlas of medicines. – M.: SIA International LTD. TF MIR: Eksmo Publishing House, 2008. - 992 p., ill.

5. N.I. Fedyukovich Reference book on medicines: at 2 pm Ch. P.. - Mn .: Interpressservis; Book House, 2008 - 544 p.

6.D.A.Kharkevich Pharmacology with a common formulation: A textbook for medical schools and colleges. - M,: GEOTAR - MED, 2008, - 408 p., ill.
Electronic resources:

1.Electronic library by discipline. Lecture on the topic "Cholinomimetics".

International name: Pilocarpine (Pilocarpine)

Dosage form:

Pharmachologic effect:

Indications:

Oftan Pilocarpine

International name: Pilocarpine (Pilocarpine)

Dosage form: eye drops, eye ointment, eye films

Pharmachologic effect: M-cholinostimulating agent, has a miotic and antiglaucoma effect. Increases the secretion of digestive, bronchial and sweat...

Indications: Acute attack of angle-closure glaucoma, secondary glaucoma (thrombosis of the central retinal vein, acute obstruction of the retinal arteries, atrophy ...

Pilaren

Dosage form: eye films

Pharmachologic effect: Pilaren is a combination drug. Pilocarpine is a peripheral m-holinostimulator; improves the outflow of aqueous humor from the eye, lowers intraocular...

Indications: Open angle glaucoma.

Pilogel

International name: Pilocarpine (Pilocarpine)

Dosage form: eye drops, eye ointment, eye films

Pharmachologic effect: M-cholinostimulating agent, has a miotic and antiglaucoma effect. Increases the secretion of digestive, bronchial and sweat...

Indications: Acute attack of angle-closure glaucoma, secondary glaucoma (thrombosis of the central retinal vein, acute obstruction of the retinal arteries, atrophy ...

Pilocarpine

International name: Pilocarpine (Pilocarpine)

Dosage form: eye drops, eye ointment, eye films

Pharmachologic effect: M-cholinostimulating agent, has a miotic and antiglaucoma effect. Increases the secretion of digestive, bronchial and sweat...

Indications: Acute attack of angle-closure glaucoma, secondary glaucoma (thrombosis of the central retinal vein, acute obstruction of the retinal arteries, atrophy ...

Pilocarpine optifilm

International name: Pilocarpine (Pilocarpine)

Dosage form: eye drops, eye ointment, eye films

Pharmachologic effect: M-cholinostimulating agent, has a miotic and antiglaucoma effect. Increases the secretion of digestive, bronchial and sweat...

Indications: Acute attack of angle-closure glaucoma, secondary glaucoma (thrombosis of the central retinal vein, acute obstruction of the retinal arteries, atrophy ...

Pilocarpine with methylcellulose

International name: Pilocarpine (Pilocarpine)

Dosage form: eye drops, eye ointment, eye films

Pharmachologic effect: M-cholinostimulating agent, has a miotic and antiglaucoma effect. Increases the secretion of digestive, bronchial and sweat...

Indications: Acute attack of angle-closure glaucoma, secondary glaucoma (thrombosis of the central retinal vein, acute obstruction of the retinal arteries, atrophy ...

Pilocarpine hydrochloride

International name: Pilocarpine (Pilocarpine)

Dosage form: eye drops, eye ointment, eye films

Pharmachologic effect: M-cholinostimulating agent, has a miotic and antiglaucoma effect. Increases the secretion of digestive, bronchial and sweat...

Indications: Acute attack of angle-closure glaucoma, secondary glaucoma (thrombosis of the central retinal vein, acute obstruction of the retinal arteries, atrophy ...

Pilocarpine hydrochloride with methylcellulose

International name: Pilocarpine (Pilocarpine)

Dosage form: eye drops, eye ointment, eye films

Pharmachologic effect: M-cholinostimulating agent, has a miotic and antiglaucoma effect. Increases the secretion of digestive, bronchial and sweat...

Indications: Acute attack of angle-closure glaucoma, secondary glaucoma (thrombosis of the central retinal vein, acute obstruction of the retinal arteries, atrophy ...

M-cholinergic receptors

N-cholinergic receptors

myocytes interact with Gj-proteins that inhibit adenylate cyclase. When they are stimulated in cells, cAMP synthesis decreases and, as a result, the activity of cAMP-dependent protein kinase, which phosphorylates proteins, decreases. Phosphorylation of calcium channels is disturbed in cardiomyocytes - as a result, less Ca2 + enters the cells of the sinoatrial node in phase 4 of the action potential. This leads to a decrease in the automatism of the sinoatrial node and, consequently,
to a decrease in heart rate. Other indicators of the work of the heart also decrease (see Table 8.1).
M3-cholinergic receptors of smooth muscle cells and cells of exocrine glands interact with Gq-proteins that activate phospholipase C. With the participation of this enzyme, inositol-1,4,5-triphosphate (1P3) is formed from phospholipids of cell membranes, which promotes the release of Ca2+ from sarcoplasmic reticulum (intracellular calcium depot). As a result, when M3-cholinergic receptors are stimulated, the Ca2+ concentration in the cell cytoplasm increases, which causes an increase in the tone of the smooth muscles of the internal organs and an increase in the secretion of exocrine glands. In addition, non-innervated (extrasynaptic) M3 cholinergic receptors are located in the membrane of vascular endothelial cells. Their stimulation increases the release of endothelial relaxing factor (N0) from endothelial cells, which causes relaxation of vascular smooth muscle cells. This leads to a decrease in vascular tone and a decrease in blood pressure.
M,-cholinergic receptors are coupled to Gq-proteins. Stimulation of M,-cholinergic receptors of enterochromaffin-like cells of the stomach leads to an increase in the concentration of cytoplasmic Ca2+ and an increase in the secretion of histamine by these cells. Histamine, in turn, acting on the parietal cells of the stomach, stimulates the secretion of hydrochloric acid. Subtypes of M-cholinergic receptors and the effects caused by their stimulation are presented in table. 8.1.
The prototype of M-cholinomimetics is the alkaloid muscarine contained in fly agaric mushrooms. Muscarine causes effects associated with the stimulation of all subtypes of M-cholinergic receptors shown in Table. 8.1. Muscarine does not penetrate the blood-brain barrier and therefore does not have a significant effect on the central nervous system. Muscarine is not used as a drug. When poisoned with fly agaric containing muscarine, its toxic effect is manifested, associated with the excitation of M-cholinergic receptors. At the same time, constriction of the pupils, spasm of accommodation, profuse salivation and sweating, increased tone of the bronchi and secretion of the bronchial glands (which is manifested by a feeling of suffocation), bradycardia and a decrease in blood pressure, spastic pain in the abdomen, diarrhea, nausea and vomiting are noted. In case of fly agaric poisoning, gastric lavage is performed and saline laxatives are given. To eliminate the action of muscarine, the M-cholinergic blocker atropine is used.

N
Aceclidine

С2Н5- CH- CH - CH2 ~ C N - CH3
* ° і і * and і °


Pilocarpine hydrochloride
Acetylcholine

Pilocarpine is an alkaloid from the leaves of the Pilocarpus pinnatifolius Jaborandi shrub native to South America. Pilocarpine used in medical practice is obtained synthetically. Pilocarpine has a direct stimulating effect on M-cholinergic receptors and causes all the effects characteristic of drugs in this group (see Table 8.1). Especially strongly pilocarpine increases the secretion of the glands, so it is sometimes prescribed orally for xerostomia (dryness of the oral mucosa). But since pilocarpine has a fairly high toxicity, it is mainly used topically in the form of ophthalmic dosage forms to reduce intraocular pressure.
funds
radial muscle


Decreased outflow of intraocular fluid
NORM
lens
Zinn's ligament M-cholinergic receptor Ciliary muscle
The value of intraocular pressure mainly depends on two processes: the formation and outflow of intraocular fluid (aqueous moisture of the eye), which is produced by the ciliary body, and flows mainly through the drainage system of the anterior chamber angle of the eye (between the iris and cornea). This drainage system includes the trabecular meshwork (the pectinate ligament) and the venous sinus of the sclera (Schlemm's canal). Through the slit-like spaces between the trabeculae (fountain spaces) of the trabecular network, the fluid is filtered into the Schlemm canal, and from there it flows through the collector vessels into the superficial veins of the sclera (Fig. 8.2).
Spasm of accommodation NORM Paralysis of accommodation
Rice. 8.2. The effect on the eye of substances that affect cholinergic innervation (the thickness of the arrow shows the intensity of the outflow of intraocular fluid).

It is possible to reduce intraocular pressure by reducing the production of intraocular fluid and / or increasing its outflow. The outflow of intraocular fluid largely depends on the size of the pupil, which is regulated by two muscles of the iris: the circular muscle (m. sphincter pupillae) and the radial muscle (t. dilatator pupillae). The circular muscle of the pupil is innervated by parasympathetic fibers (n. oculomotorius), and the radial muscle is innervated by sympathetic fibers (n. sympaticus). With the contraction of the circular muscle, the pupil narrows, and with the contraction of the radial muscle, it expands.
Pilocarpine, like all M-cholinomimetics, causes contraction of the circular muscle of the iris and constriction of the pupils (miosis). In this case, the iris becomes thinner, which contributes to the opening of the angle of the anterior chamber of the eye and the outflow of intraocular fluid through the fountain spaces into the Schlemm's canal. This leads to a decrease in intraocular pressure.
The ability of pilocarpine to reduce intraocular pressure is used in the treatment of glaucoma - a disease characterized by a constant or periodic increase in intraocular pressure, which can lead to atrophy of the optic nerve and loss of vision. Glaucoma is open-angle and closed-angle. The open-angle form of glaucoma is associated with a violation of the drainage system of the angle of the anterior chamber of the eye, through which the outflow of intraocular fluid is carried out; the corner itself is open. The angle-closure form develops when there is a violation of access to the angle of the anterior chamber of the eye, most often when it is partially or completely closed by the root of the iris. Intraocular pressure may rise to 60-80 mm Hg. (normal intraocular pressure ranges from 16 to 26 mm Hg).
Due to the ability to narrow the pupils (miotic action), pilocarpine is highly effective in the treatment of angle-closure glaucoma and in this case is used in the first place (it is the drug of choice). Pilocarpine is also prescribed for open-angle glaucoma. Pilocarpine is used in the form of 1-2% aqueous solutions (duration of action - 4-8 hours), solutions with the addition of polymer compounds that have a prolonged effect (8-12 hours), ointments and special eye films made of polymer material (eye films with pilocarpine are laid for the lower eyelid 1-2 times a day).
Pilocarpine causes contraction of the ciliary muscle, which leads to relaxation of the ligament of Zinn, which stretches the lens. The curvature of the lens increases, it acquires a more convex shape. With an increase in the curvature of the lens, its refractive power increases - the eye is set to the near point of view (objects that are near are better seen). This phenomenon, called accommodation spasm, is a side effect of pilocarpine. When instilled into the conjunctival sac, pilocarpine is practically not absorbed into the blood and does not have a noticeable resorptive effect.
Aceclidine is a synthetic compound with a direct stimulating effect on M-cholinergic receptors and causes all the effects associated with the excitation of these receptors (see Table 8.1).
Aceclidine can be applied topically (installed in the conjunctival sac) to lower intraocular pressure in glaucoma. After a single instillation, the decrease in intraocular pressure lasts up to 6 hours. However, aceclidine solutions have a local irritant effect and can cause irritation of the conjunctiva.

Due to the lower toxicity compared to pilocarpine, aceclidine is used for resorptive action in atony of the intestines and bladder. Side effects: salivation, diarrhea, spasms of smooth muscle organs. Due to the fact that aceclidin increases the tone of the smooth muscles of the bronchi, it is contraindicated in bronchial asthma.
In case of an overdose of M-cholinomimetics, their antagonists are used - M-cholinergic blockers (atropine and atropine-like drugs).
N-cholinomimetics
This group includes alkaloids nicotine, lobelia, cytisine, which act mainly on neuronal-type H-cholinergic receptors localized on neurons of sympathetic and parasympathetic ganglia, chromaffin cells of the adrenal medulla, in carotid glomeruli and in the central nervous system. These substances act on H-cholinergic receptors of skeletal muscles in much higher doses.
N-cholinergic receptors are membrane receptors that are directly associated with ion channels. Structurally, they are glycoproteins and consist of several subunits. So the H-cholinergic receptor of neuromuscular synapses includes 5 protein subunits (a, a, (3, y, 6) that surround the ion (sodium) channel. When two molecules of acetylcholine bind to a-subunits, the Na + channel opens Na + ions enter the cell, which leads to depolarization of the postsynaptic membrane of the skeletal muscle end plate and muscle contraction.
CH
"-" Pz
Lobeline hydrochloride
Nicotine is an alkaloid found in the leaves of tobacco (Nicotiana tabacum, Nicotiana rustica). Basically, nicotine enters the human body while smoking tobacco, about 3 mg during smoking one cigarette (lethal dose of nicotine is 60 mg). It is rapidly absorbed from the mucous membranes of the respiratory tract (it also penetrates well through intact skin). /> Nicotine stimulates H-cholinergic receptors of sympathetic and parasympathetic ganglia, chromaffin cells of the adrenal medulla (increases the release of adrenaline and noradrenaline) and carotid glomeruli (stimulates the respiratory and vasomotor centers). Stimulation of the sympathetic ganglia, adrenal medulla, and carotid glomeruli leads to the most characteristic effects of nicotine on the part of the cardiovascular system: an increase in heart rate, vasoconstriction, and an increase in blood pressure. Stimulation of the parasympathetic ganglia causes an increase in intestinal tone and motility and an increase in the secretion of exocrine glands (large doses of nicotine have a depressing effect on these processes). Stimulation of the H-cholinergic receptors of the parasympathetic ganglia is also the cause of bradycardia, which can be observed at the onset of nicotine action.
Since nicotine is highly lipophilic (a tertiary amine), it quickly crosses the blood-brain barrier into the brain tissue. In the CNS, nicotine causes the release of dopamine, some other biogens
amines and excitatory amino acids, which is associated with subjective pleasant sensations that occur in smokers. In small doses, nicotine stimulates the respiratory center, and in large doses it causes its oppression up to respiratory arrest (paralysis of the respiratory center). In high doses, nicotine causes tremors and seizures. Acting on the trigger zone of the vomiting center, nicotine can cause nausea and vomiting.
Nicotine is primarily metabolized in the liver and excreted by the kidneys unchanged and as metabolites. Thus, it is quickly eliminated from the body (t] / 2 - 1.5-2 hours). Tolerance (addiction) quickly develops to the action of nicotine.
Acute nicotine poisoning can occur when nicotine solutions come into contact with the skin or mucous membranes. In this case, hypersalivation, nausea, vomiting, diarrhea, bradycardia, and then tachycardia, increased blood pressure, first shortness of breath, and then respiratory depression, convulsions are noted. Death occurs from paralysis of the respiratory center. The main measure of assistance is artificial respiration.
When smoking tobacco, chronic nicotine poisoning is possible, as well as other toxic substances that are contained in tobacco smoke and can have an irritating and carcinogenic effect. For most smokers, inflammatory diseases of the respiratory tract, such as chronic bronchitis, are typical; lung cancer is more common. The risk of cardiovascular diseases increases.
Mental dependence develops to nicotine, therefore, when smoking is stopped, smokers experience a withdrawal syndrome, which is associated with the occurrence of painful sensations and a decrease in working capacity. To reduce the withdrawal syndrome, it is recommended to use chewing gum containing nicotine (2 or 4 mg) or a transdermal therapeutic system (a special skin patch that releases small amounts of nicotine evenly over 24 hours) during the period of quitting smoking.
In medical practice, the N-cholinomimetics of lobelia and cytisine are sometimes used.
Lobelia - the alkaloid of the plant Lobelia inflata is a tertiary amine. By stimulating the H-cholinergic receptors of the carotid glomeruli, lobelia reflexively excites the respiratory and vasomotor centers.
Cytisine, an alkaloid found in broom (Cytisus laburnum) and thermopsis (Thermopsis lanceolata) plants, is a secondary amine in structure. It is similar in action to lobelin, but excites the respiratory center somewhat more strongly.
Cytisine and Lobelia are part of the Tabex and Lobesil tablets, which are used to facilitate smoking cessation. The drug cytiton (0.15% solution of cytisine) and a solution of lobeline are sometimes administered intravenously for reflex stimulation of breathing. However, these drugs are effective only if the reflex excitability of the respiratory center is preserved. Therefore, they are not used for poisoning with substances that reduce the excitability of the respiratory center (hypnotics, narcotic analgesics).

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 and dams, local anesthetics.

Acetylcholine is incompatible with mezaton.

Introduction to a 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 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.

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