This group includes nicotine, lobelia, and cytisine alkaloids, which act predominantly 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 N-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 α-subunits, the Na + channel opens Na + ions enter the cell, which leads to depolarization of the postsynaptic membrane of the end plate of skeletal muscles and muscle contraction.

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 mucous membranes respiratory tract(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 results in the most characteristic cardiovascular effects of nicotine: increased heart rate, vasoconstriction, and increased 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 beginning of the action of nicotine.

Since nicotine is highly lipophilic (a tertiary amine), it quickly crosses the blood-brain barrier into brain tissue. In the central nervous system, nicotine causes the release of dopamine, some other biogenic

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), 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 ( sleeping pills, narcotic analgesics).

Drugs of this group have a direct stimulating effect on M-cholinergic receptors located at the endings of postganglionic parasympathetic nerve fibers. As a result, they reproduce the effects of acetylcholine associated with the excitation of parasympathetic innervation: pupil constriction (miosis), spasm of accommodation (the eye is set to near vision), bronchial constriction, profuse salivation, increased secretion of bronchial, digestive and sweat glands, increased motility gastrointestinal tract, increased tone Bladder, bradycardia.

Fig.7. The effect of cholinomimetics on the eye (The number of arrows indicates the intensity of the outflow of intraocular fluid)

Pilocarpine - alkaloid plant origin. Synthetically obtained, it is available in the form of pilocarpine hydrochloride. Its effect is to reduce intraocular pressure, is used to treat glaucoma (increased intraocular pressure up to 50-70mm Hg). The use of pilocarpine causes constriction of the pupil due to contraction of the circular muscle of the iris, facilitates the outflow of fluid from the anterior chamber of the eye to the back due to the contraction of the ciliary muscle. At the same time, a spasm of accommodation develops (the curvature of the lens increases). (Fig.11).

Pilocarpine is used only locally, because. is quite toxic. Used for glaucoma, atrophy optic nerve, to improve eye trophism, etc. It has a slight irritating effect. Included in the combined eye drops Fotil, Pilotim.

N - cholinomimetics

The sensitivity of H-cholinergic receptors of different localization to chemicals is not the same due to differences in their structure.

N-cholinomimetics (cytiton, lobelin) excite N-cholinergic receptors of carotid sinus glomeruli, which leads to reflex stimulation of the respiratory and vasomotor centers. There is an increase and deepening of breathing. Simultaneous excitation of synaptic nodes and adrenal glands leads to an increase in the release of adrenaline and an increase in blood pressure.

Cytiton and Lobelina hydrochloride are reflex action stimulants of respiration and can be used for reflex respiratory arrest (carbon monoxide poisoning, drowning, suffocation, electrical injuries, etc.), and neonatal asphyxia.

More widely, these substances are used to treat tobacco smoking. As part of Tabex tablets (cytisine), it is used to facilitate smoking cessation. For this purpose, small doses of nicotine are also used (Nicorette chewing gums, Nicotinell patch). These medicines reduce physical dependence on nicotine.

Tobacco alkaloid - nicotine is also an N-cholinomimetic, but is not used as a drug. Penetrates the body when smoking tobacco and has a variety of effects. Nicotine affects both peripheral and central H-cholinergic receptors, and has a two-phase effect: the first stage - excitation - is replaced by a depressing effect. The constant effect of nicotine is its vasoconstrictive effect, due to the fact that nicotine stimulates the H-cholinergic receptors of the sympathetic ganglia, chromaffin cells of the adrenal glands and the carotid sinus zone, stimulates the release of adrenaline and reflexively excites the vasomotor center. In this regard, nicotine increases blood pressure and contributes to the development hypertension. severe vascular disease lower extremities- obliterating endarteritis - occurs almost exclusively in smokers. Nicotine narrows the blood vessels of the heart and contributes to the development of angina pectoris, myocardial infarction, tachycardia. Serious changes are observed from the side of the central nervous system. Exhibits nicotine and carcinogenic effects.

M, N - cholinomimetics

These substances simultaneously stimulate M- and H-cholinergic receptors and directly or indirectly affect the executive organs. There are M, N-cholinomimetics of direct and indirect action.

Direct-acting drugs include Acetylcholine and Carbachol (Carbachol). They directly stimulate postsynaptic receptors. As a drug, acetylcholine is practically not used, because. it works for a short time (several minutes). It is used in experimental pharmacology.

In medical practice, an analogue of acetylcholine, Carbacholin, is sometimes used for glaucoma in the form of eye drops. It differs from acetylcholine in greater durability and acts longer (up to 1-1.5 hours), because. not hydrolyzed by acetylcholinesterase.

Anticholinesterase agents (M, N - indirect cholinomimetics).

These substances inhibit the activity of the enzyme acetylcholinesterase and increase the effect of acetylcholine on M- and H-cholinergic receptors. The effects of anticholinesterase agents are basically similar to those of direct M,N-cholinomimetics. M-cholinomimetic action is manifested in an increase in the tone and contractile activity of smooth muscles (bronchus, gastrointestinal tract, bladder, circular muscle of the iris, etc.), in increased secretion of glands (bronchial, digestive, sweat, etc.), in the occurrence of bradycardia and a drop in blood pressure. N-cholinomimetic action is manifested in the stimulation of neuromuscular conduction. In small doses, anticholinesterase drugs stimulate the central nervous system, and in large doses they depress.

Tertiary amines (physostigmine, galantamine) penetrate biological membranes, including the BBB, and have a pronounced effect on the central nervous system. Quaternary ammonium derivatives (prozerin, pyridostigmine, distigmine) are difficult to penetrate through the BBB.

Inhibition of acetylcholinesterase is carried out due to the interaction of substances with the same sites of the enzyme with which acetylcholine binds. This relationship can be reversible or irreversible.

Neostigmine (prozerin) - a synthetic drug, is a quaternary ammonium compound, does not penetrate the BBB and has a predominant effect in peripheral tissues. It is used for myasthenia gravis, muscular dystrophy, paralysis, motor disorders associated with neuritis, polyneuritis, residual effects after brain injuries, poliomyelitis, meningitis, encephalitis, as well as atony of the intestines and bladder, weak labor activity. Prozerin is an antagonist of M-cholinergic blockers and curare-like drugs with an antidepolarizing type of action. Contraindicated in epilepsy bronchial asthma, angina pectoris, atherosclerosis, pregnancy.

Galantamine (nivalin) is an alkaloid found in snowdrop tubers. Available as galantamine hydrobromide. It is a tertiary amine, penetrates through the BBB and has a central activity. Physostigmine (physostigmine salicylate) has similar properties.

It is used for polyneuritis, cerebral circulation disorders, poliomyelitis, cerebral palsy, dementia (memory impairment), myasthenia gravis, atony internal organs.

Distigmine bromide (ubretide), Pyridostigmine bromide (kalimin) - synthetic drugs that reversibly inhibit acetylcholinesterase. They are used for atony of the intestines and bladder, myasthenia gravis, paralysis of the striated muscles.

Due to the phosphorylation of acetylcholinesterase, an irreversible inhibition of its activity for a long time is carried out. This effect is possessed by organophosphorus compounds (OPs), of which medical application in the treatment of glaucoma, Phosphacol and Armin were purchased in the form of eye drops.

But FOS also includes a large group of insecticides used to kill insects (chlorophos, karbofos, dichlorvos, etc.), as well as used in agriculture fungicides, herbicides, etc.

When they are used, poisonings often occur, which have the following symptoms: miosis (constriction of the pupil), salivation, sweating, vomiting, bronchospasm, diarrhea. Convulsions, psychomotor agitation, coma and respiratory arrest may occur. In case of acute OP poisoning, first of all, it is necessary to remove the toxic substance from the injection site, wash the skin with 3-5% sodium bicarbonate solution. If FOS is ingested, rinse the stomach, give laxatives and adsorbents. If FOS entered the blood, then forced diuresis, hemosorption, hemodialysis are carried out.

As functional antagonists in case of FOS poisoning, M-anticholinergics (atropine, etc.), as well as cholinesterase reactivators - dipyroxime and isonitrosine, are used. They bind to FOS, destroy the phosphorus-enzyme bond and restore the activity of the enzyme. These drugs are effective only in the first hours after poisoning.

Anticholinergics

Anticholinergic or anticholinergic agents are substances that weaken, prevent or stop the interaction of acetylcholine with cholinergic receptors. By blocking receptors, they act opposite to acetylcholine.

M - anticholinergics

Drugs of this group block M - cholinergic receptors and prevent the interaction of the acetylcholine mediator with them. This eliminates (blocks) parasympathetic innervation organs and there are corresponding effects: a decrease in the secretion of salivary, sweat, bronchial, digestive glands, bronchial dilatation, decreased tone of smooth muscles and peristalsis of internal organs, tachycardia and increased heart rate; at topical application cause pupil dilation (mydriasis), accommodation paralysis (vision is set to distant vision), increased intraocular pressure.

Non-selective M - anticholinergics

They affect peripheral and central M-cholinergic receptors. Among them are herbal and synthetic drugs.

Atropine is an alkaloid of a number of plants from the nightshade family: belladonna, dope, henbane, etc. It is produced in the form of atropine sulfate. Is a racemate, is a mixture of L- and D-isomers of hyoscyamine. It is also obtained synthetically. Causes all of the above effects. Particularly pronounced in atropine are antispasmodic properties, effects on the eye, secretion of glands, the conduction system of the heart. In high doses, atropine stimulates the cerebral cortex and can cause motor and speech restlessness.

Atropine is used for peptic ulcer stomach and duodenum, with spasms of the intestines and urinary tract, with bronchial asthma, with bradycardia and atrioventricular heart block, with excessive sweating, to reduce salivation in Parkinson's disease, for premedication before anesthesia due to its ability to suppress the secretion of the salivary and bronchial glands, in case of poisoning with M-cholinomimetics and anticholinesterase agents.

In ophthalmic practice, atropine is used to dilate the pupil for diagnostic purposes and in acute inflammatory diseases and eye injuries. The maximum expansion of the pupil occurs in 30-40 minutes and lasts 7-10 days. The atropine-like drugs Homatropin (15-20 hours) and Tropicamide (2-6 hours) act less long.

Undesirable effects of atropine are associated with its M-anticholinergic action: dryness of the mouth, skin, visual impairment, tachycardia, voice change, impaired urination, constipation. Decreased sweating can lead to an increase in body temperature.

Atropine and M-anticholinergics are contraindicated in glaucoma, hypersensitivity to them, fever, in the hot season (due to the possibility of "heat stroke").

When poisoning with atropine, dryness of the oral mucosa, nasopharynx, impaired swallowing, speech are noted; dryness and hyperemia of the skin, fever, dilated pupils, photophobia (photophobia). Characterized by motor and speech excitement, delirium, hallucinations.

Poisoning occurs when an overdose of drugs or when eating parts of a plant containing alkaloids. Help for acute poisoning is to wash the stomach, use saline laxatives, activated charcoal, diuretics. With severe arousal, diazepam and other drugs that depress the central nervous system are used. Functional antagonists from the group of anticholinesterase agents, physostigmine salicylate, are also administered.

From drugs containing atropine, belladonna (belladonna) preparations obtained from the leaves and herbs of this plant are also used. Belladonna tincture, tablets "Bekarbon", "Besalol", "Bepasal", "Bellalgin", "Bellastezin" are used for spasmodic pains of the gastrointestinal tract. The belladonna extract is part of the suppositories "Betiol", "Anuzol", used for hemorrhoids and cracks anus. Tablets "Bellataminal", "Bellaspon", containing the amount of belladonna alkaloids, are used for increased irritability, neuroses, etc.

Scopolamine (hyoscine) is an atropine-like alkaloid of the same plants. It has pronounced M-anticholinergic properties, has more strong action on the eye and secretion of the glands. Unlike atropine, it depresses the central nervous system, causes sedation and drowsiness, acts on the extrapyramidal system and the vestibular apparatus. Available as scopolamine hydrobromide.

It is used for the same indications as atropine, as well as for sea and air sickness (part of the Aeron tablets). Antiemetic action during motion sickness is also possessed by Avia-Sea, Lokomotiv.

Platifillin is a ragwort alkaloid. It is used in the form of hydrotartrate salt. It has a more pronounced peripheral antispasmodic effect. Used mainly for spasms of the stomach, intestines, bile ducts, ureters.

Metocinium iodide (methacin) is a synthetic M-holinoblokator. Poorly penetrates the blood-brain barrier, does not affect the central nervous system. By its effect on the bronchial muscles, it is more active than atropine, it suppresses the secretion of the salivary and bronchial glands more strongly. Relaxes the muscles of the esophagus, intestines, stomach, but has a significantly lesser mydriatic effect than atropine.

Metacin is used for spasms of smooth muscle organs. Effective in the treatment of renal and hepatic colic. Unwanted side effects are less common.

Selective M - anticholinergics

Pirenzepine (gastrozepin, gastril) selectively blocks M1-cholinergic receptors of the stomach and suppresses secretion of hydrochloric acid. Applied with peptic ulcer of the stomach and duodenum, hyperacid gastritis. Undesirable side effects are rare: dry mouth, dyspepsia, slight disturbance of accommodation. Contraindicated in glaucoma.

Ipratropium bromide (Atrovent), Tiotropium bromide (Spiriva) - block the M-cholinergic receptors of the bronchi, have a bronchodilator effect, reduce the secretion of the glands. Used for bronchial asthma. Ipratropium is part of the combined aerosols "Berodual", "Combivent". Undesirable side effects: dry mouth, increased sputum viscosity, allergic reactions.

N - anticholinergics

This group includes ganglioblocking agents and blockers of neuromuscular synapses.

Ganglioblockers

These substances block the H-cholinergic receptors of the autonomic ganglia, the adrenal medulla, and the carotid sinus zone. At the same time, N-cholinergic receptors of sympathetic and parasympathetic nerves simultaneously. Due to the inhibition of the sympathetic ganglia, the transmission of impulses to the blood vessels is disrupted, as a result of which the vessels dilate, arterial and venous pressure decreases. The expansion of peripheral vessels leads to an improvement in blood circulation in them. With the blockade of parasympathetic ganglia, the secretion of glands (sweat, salivary, digestive) decreases, the muscles of the bronchi relax, and the motility of the digestive tract is inhibited.

Hexamethonium (benzohexonium) is a quaternary ammonium compound with strong ganglioblocking activity. More active when administered parenterally. It is used for spasms of peripheral vessels (endarteritis, Raynaud's disease, etc.), for controlled hypotension during operations, for edema of the lungs, brain (against the background of high blood pressure), less often for gastric ulcer, bronchial asthma, intestinal spasms, etc., hypertension.

With the introduction of hexamethonium and other ganglionic blockers, the development of orthostatic collapse is possible. To prevent it, patients are recommended to lie down for 1-2 hours after the injection of the ganglioblocker. At the phenomena of a collapse it is necessary to enter - adrenomimetic means.

When using benzohexonium, it is also possible general weakness, dizziness, dry mouth, tachycardia, dilated pupils, respiratory depression, constipation, impaired urination.

Drugs are contraindicated in hypotension, in acute myocardial infarction, in kidney and liver damage, in thrombosis, degenerative changes in the central nervous system. Caution is needed when prescribing to the elderly.

Trepirium iodide (hygronium) and trimetafan (arfonad) have a short-term ganglioblocking effect. They are used for controlled hypotension and for the relief of hypertensive crises. They are injected into a vein by drip.

Currently, ganglioblockers are rarely used.

Muscle relaxants (from Greek - mys - muscles, lat. - relaxio - weakening) (curare-like drugs)

Drugs of this group selectively block N-cholinergic receptors in neuromuscular synapses and cause relaxation of skeletal muscles. They are called curariform means by the name of the arrow poison "curare", used by the Indians during the hunt to immobilize animals.

According to the mechanism of action, there are two groups of muscle relaxants: non-depolarizing (antidepolarizing) and depolarizing.

Most drugs are antidepolarizing. They interact with H-cholinergic receptors of the postsynaptic membrane of neuromuscular synapses and prevent the depolarizing action of acetylcholine. Their antagonists are anticholinesterase agents (neostigmine, galantamine): inhibiting cholinesterase activity in appropriate doses, they contribute to the accumulation of acetylcholine in the synapse area, with an increase in the concentration of which, the interaction of curare-like substances with H-cholinergic receptors is weakened and neuromuscular conduction is restored. These include Tubocurarine chloride, Diplacin, Pancuronium bromide (Pavulon), Pipecuronium bromide (Arduan) and others. These drugs are used to relax the muscles during surgery, during tracheal intubation, during reposition of bone fragments, with convulsions, tetanus, to reduce dislocations.

Curare-like drugs relax the muscles in a certain sequence: first, the muscles of the face and neck relax, then the limbs and torso, and lastly, the intercostal muscles and the diaphragm, which is accompanied by respiratory arrest.

Another group of drugs is depolarizing muscle relaxants. They cause persistent depolarization of the postsynaptic membrane, while repolarization occurs and subsequent impulses do not pass. Drugs of this group are relatively quickly hydrolyzed by cholinesterase and have a short-term effect after a single administration. They don't have antagonists. Such a drug is Suxamethonium chloride (ditilin, listenone). It is injected into a vein. It quickly and briefly relaxes the skeletal muscles. For longer muscle relaxation, reintroduction LS.

When using muscle relaxants of both groups, as a rule, paralysis of the respiratory muscles develops, therefore their use is allowed only if there are conditions for artificial respiration.

Of the undesirable side effects, a decrease in blood pressure and bronchospasm are sometimes noted. Contraindicated in myasthenia gravis, it should be used with caution in violation of the function of the kidneys and liver, as well as in old age.

M, N - anticholinergics

These drugs have a peripheral and central M-anticholinergic effect. Central action contributes to the reduction or elimination movement disorders(tremor, rigidity) associated with damage to the extrapyramidal system. Trihexyphenidyl (cyclodol, parkopan) has been widely used in the treatment of Parkinson's disease. When using drugs, you may experience side effects associated with its anticholinergic properties: dry mouth, disturbance of accommodation, increased heart rate, dizziness. HP is contraindicated in glaucoma, heart disease, the elderly.

Classification by mechanism of action

I. m-, n-cholinomimetic agents (excite both m- and n-cholinergic receptors):

1. Direct type of action acetylcholine, carbachol;

2. Indirect type of action (anticholinesterase agents): prozerin, galantamine hydrobromide, physostigmine salicylate, pyridostigmine bromide, etc.

II. m Cholinomimetics (excite m-cholinergic receptors): muscarine, pilocarpine hydrochloride, aceclidine.

III. n-cholinomimetic agents (excite n-cholinergic receptors): nicotine, cytiton.

Means stimulating m- and n-cholinergic receptors (m-, n-cholinomimetics)

This group includes drugs of the direct type of action - acetylcholine and carbacholin (acetic and carbamic esters of choline) and indirect type of action - anticholinesterase agents.

When m-, n-cholinomimetics are introduced into the body, the effects associated with the excitation of the parasympathetic nervous system. In medical practice, they are used to a limited extent. Acetylcholine chloride is very quickly destroyed by cholinesterase and is practically not used as a drug. This tool is mainly used in experimental pharmacology. Unlike acetylcholine, carbacholine is NOT hydrolyzed by true cholinesterase and exhibits a longer duration of action. The drug is prescribed in ophthalmic practice to reduce intraocular pressure in glaucoma.

Unlike direct, indirect m-, n-cholinomimetics, better known as "anticholinesterase agents", are widely used in medical practice.

Based on the name of this group, the mechanism of action of drugs is the blockade of cholinesterase, an enzyme that destroys acetylcholine. Structurally similar to acetylcholine, these drugs bind to cholinesterase. As a result, a mediator accumulates in cholinergic synapses, which leads to the development of cholinomimetic actions. Excitation of m cholinergic receptors leads to pupil constriction, a decrease in intraocular pressure, a spasm of accommodation, an increase in the contractile function of the unsmooth (smooth) muscle tissue of the digestive tract, bronchi, uterus, bladder, an increase in the secretion of glands (salivary, digestive, sweat, etc.), a decrease in the frequency heart contractions. The decrease in blood pressure occurs due to the formation of nitric oxide. Excitation of n-cholinergic receptors facilitates nerve impulse to skeletal muscles and enhances their contractility.

The strength and duration of action of anticholinesterase agents is determined by the stability of their complex with the enzyme. Substances that, when interacting with cholinesterase, form a complex, slowly decompose, cause a temporary, relatively short, reversible suppression of enzyme activity. After the end of the action of drugs, cholinesterase activity is restored. When using substances that form a complex with the enzyme, it is not capable of dissociation (irreversible inhibition), an independent process of acetylcholine hydrolysis begins after the biosynthesis of a new cholinesterase, and the activity of blocked cholinesterase can be restored only when special reactivators are used. Based on the foregoing, anticholinesterase drugs are divided into two groups: reversible and irreversible actions.

Reversible anticholinesterase agents include physostigmine salicylate, galantamine hydrobromide, rivastigmine (tertiary nitrogen compounds), which are well absorbed in the gastrointestinal tract, penetrate the blood-brain barrier and act on the central nervous system, as well as neostigmine (prozerin), pyridostigmine bromide, distigmine bromide (quaternary nitrogen-containing substances ), which are poorly absorbed when administered enterally, do not cross the blood-brain barrier, practically do not change the function of cholinergic synapses of internal organs and autonomic ganglia, but significantly improve neuromuscular transmission.

Reversible anticholinesterase agents are prescribed for the treatment of:

1) glaucoma (except for galantamine, which has a local irritant effect)

2) postoperative atony of the intestines and bladder (for this purpose, it is advisable to use quaternary amines that do not penetrate the central nervous system);

3) myasthenia gravis (weakness of skeletal and facial muscles due to impaired neuromuscular impulse transmission)

4) diseases of the peripheral nervous system (flaccid paralysis, paresis, neuritis, polyneuritis)

5) muscle paralysis associated with dysfunction of the brain and spinal cord(after trauma, stroke, poliomyelitis) use a tertiary amine, galantamine hydrobromide, which penetrates the central nervous system

6) an overdose of anti-depolarizing (non-depolarizing) muscle relaxants, prozerin is most often used as a drug of peripheral and short-term action;

7) in dental practice - dry mouth (xerostomia) and neuritis of the facial nerve (galantamine hydrobromide, prozerin).

Physostigmine salicylate is the first representative of natural reversible anticholinesterase agents - a salt of the main alkaloid of Calabar beans (seeds of a West African plant, Physostigma venenosum, legume family, Fabaceae). IN last years used mainly in experimental pharmacology.

Galantamine hydrobromide (nivalin)- salt of an alkaloid isolated from the tubers of Voronov's and ordinary snowdrops (Galanthus woronowii and Galanthus nivalis, from the Amaryllis family, Amaryllidaceae). It is well absorbed in the alimentary canal and from the subcutaneous tissues, easily penetrates the blood-brain barrier. It acts like physostigmine, but its muscarinic and nicotine effects pronounced and last longer. Facilitates the conduction of excitation and neuromuscular conduction. Affects the muscles directly. Galantamine hydrobromide is used for myasthenia gravis, progressive muscular dystrophy, motor and sensory disorders associated with neuritis, polyneuritis, radiculitis, with residual effects after cerebrovascular accident, in the recovery period of acute poliomyelitis, in children cerebral palsy. Galantamine hydrobromide can be used for bowel and bladder atony. It is an antagonist of muscle relaxants with antidepolarizing action. With the introduction of a solution of galanthamine hydrobromide into the conjunctival cavity, temporary swelling of the conjunctiva may be observed.

Prozerin is a synthetic quaternary ammonium substance with a pronounced reverse anticholinesterase activity, manifested in m-and n-cholinergic synapses. At oral administration poorly absorbed in the alimentary canal (about 2% bioavailability). Does not penetrate the blood-brain barrier. It is metabolized mainly by microsomal liver enzyme. With intramuscular injection 67 % the administered dose is excreted by the kidneys unchanged.

By peripheral effects, it is close to physostigmine and galantamine, but, unlike these drugs, it does not act on central cholinergic synapses. Used for diagnosis and treatment in cases of myasthenia gravis (myasthenia gravis ), postoperative atony of the intestines and bladder, as an antagonist of anticholinergics and muscle relaxants of antidepolarizing action and in patients with glaucoma. Sometimes prozerin is prescribed for weakness of labor activity.

Pyridostigmine bromide (kalimin) is a reversible anticholinesterase agent, chemically similar to the previous drug. In terms of action on the neuromuscular transmission, motility of the digestive tract, the tone of the bladder and bronchi, it is inferior to prozerin, but it lasts longer. Causes bradycardia.

Most irreversible anticholinesterase agents are organophosphorus compounds (OPs). Substances are capable of stably phosphoruvate esterase sites of active catalytic centers of acetylcholinesterase and cause their irreversible non-conformational transformation. FOS dissolve well in lipids, quickly penetrate through intact skin and mucous membranes, and very easily into the central nervous system.

TO medicines, which are FOS, include the army and phosphatol. As medicines, FOS is used only topically for glaucoma, as they are toxic compounds for the body. In everyday life and at work, cases of poisoning with FOS (insecticides, pesticides) are quite common.

In case of an overdose of anticholinesterase drugs (poisoning with FOS), miosis, hypotension, vomiting, bronchospasm, hypersecretion of glands, bradycardia, diarrhea develop, clonic convulsions may occur, which are replaced by periods of tremor, coma. In case of an overdose of anticholinesterase agents, functional antagonists are prescribed - m-anticholinergics (atropine is injected into a vein in 2-4 ml of a 0.1% solution). In case of FOS poisoning, in addition to m anticholinergics, cholinesterase reactivators (oximes) are prescribed. Practically valuable cholinesterase reactivators of the oxime group are Alox and isonitrosine (they penetrate well through the blood-brain barrier), which are similar in the mechanism of cholinesterase reactivation, activity, method of application and efficiency. Their mechanism of action is related to physical and chemical properties reactivators, which contributes to the optimal orientation of their molecules on the molecules of acetylcholinesterase and binding to the anionic sites of the active catalytic centers of this enzyme. Subsequently, the nucleophilic centers of oximes attack the phosphorated FOS-esterase centers, as a result of which Oxy is phosphorylated, the complex thus formed is cleaved from cholinesterase and its enzymatic activity is restored. The drugs have a weak m anticholinergic effect, restore energy resources.

Pharmacological characteristics
(what you need to know about the drug in the exam)
A. General characteristics:
1. Name:
INN (INN, generic name) - Neostigmine
Trade (brand name) - Prozerin
2. Place in the pharmacological (ATS) classification:
Discharge (A, anatomy) - means acting on the peripheral nervous system,
anticholinesterase agent
Class (T, therapy) - drugs for the treatment of diseases of the nervous system.
Group (C, chemistry) - Quaternary ammonium base
B. Pharmacological properties:
1. Pharmacodynamics (effects, mechanism of the main and side effects).
2. Pharmacokinetics (absorption, distribution, metabolism, excretion).
3. Indications for use (names of diseases, conditions, or purpose
applications),
4. Side effects and contraindications.
5. Interaction with other drugs and food.
6. Laboratory criteria for evaluating the effectiveness and safety of use.
Changes in laboratory parameters under the influence of drugs
this group.
C. Forms of release and dosage

Sources of information
1. Lectures
2. Tutorial
3. Internet: rlsnet.ru
4. Directories:
"Directory
M.D. Mashkovsky,
"RLS"

Lecture plan:

*
*
Peripheral nervous system.
cholinergic synapse.
Feature: classification, mechanisms,
effects, application, individual
peculiarities.
M-cholinomimetics
N - cholinomimetics
MN-cholinomimetics

Peripheral nervous system

Cholinergic synapse

XP
Localization
M1
M5
CNS: cortex, oblong
brain, neurohypophysis,
vegetative
ganglia,
cognitive functions
Tonic activity of skeletal muscles (motor)
enterochromaffin-like
th cells of the stomach.
Histamine release, → secretion of HCl by parietal
stomach cells
a heart
↓ heart rate; inhibition of AV conduction;
↓atrial contractile activity
presynaptic
(through Gi inhibit the release of AH).
M2
smooth muscle,
M3
exocrine glands.
M3
M4
outside
vascular endothelium.
in the wall of the lung alveoli

tone (except sphincters) and motility →
cause pupillary constriction, spasm of accommodation, bronchospasm,
spasm of the bile ducts, ureters, contraction
bladder, uterus, increase intestinal motility,
relax sphincters
lacrimation, sweating, profuse separation of liquid,
protein-poor saliva, bronchorrhea, acid secretion
gastric juice
Release of endothelial relaxing factor (NO), →
relaxation of vascular smooth muscles, ↓ BP (short-term
hypotension),
have little functional value

Types and localization of cholinergic receptors

XP
Localization
Effects Caused by Stimulation
CNS: cortex,
medulla,
neurohypophysis.
cognitive functions
Tonic activity of skeletal muscles
(motor skills)
Nn
Autonomic ganglia
conducting impulses with
preganglionic fibers to
postganglionic → depolarization and
excitation of ganglionic neurons;
Nn
Medulla
adrenal glands.
secretion of epinephrine and norepinephrine
Nn
Carotid glomeruli
reflex excitation
respiratory (DC) and
vasomotor (SDC) centers
Nn
presynaptic
Nm
Skeletal muscles
Nn
release of acetylcholine
reduction

Pairing mechanisms

* M1, M3, M5 activate
phospholipase C (Fl-C) →
release of secondary
messengers - inositol
3-phosphate (IP3) and DAG;
* M2, M4 suppress
ACase activity → ↓
intracellular level
cAMP → activation of K channels.
Pairing mechanisms

10. Pairing mechanisms

The binding of acetylcholine is required to open ion channels.
two α-subunits of N-XP of the skeletal muscle end plate
→ causes the channel to open → Within milliseconds
permeability for Na \ K + and Ca2 + (through 1 channel of the membrane skeleton
muscle passes 5-107 Na + / sec) → Na + ions penetrate inside
cells, leading to depolarization of the postsynaptic membrane.
Mechanisms
conjugation

11. Acetylcholine chloride

Synthesized in 1867 by A. Beyer.
* It has a dose-dependent effect: from M-ChR stimulation to
stimulation of M and N-XP.
0.1-0.5mcg/kg affects M-ChR and causes effects
excitation of the parasympathetic system;
2-5mcg/kg affects M- and N-ChR, while Ncholinomimetic action corresponds to the effects
sympathetic system.
*
*
Rapidly destroyed by cholinesterases.
Used in experimental pharmacology.
Acetylcholine chloride

12. Cholinomimetics:

Direct d-i
Cholinomimetics:
M-hm:
M, N-xm: Carbachol
Pilocarpine
Aceclidine
(Carbachol)
acetylcholine
Indirect d-i
N-hmm:
anabasin (gamibazin),
lobeline (lobesil),
cytisine (cytiton, tabex)
nicotine (Nicorette).
AChE tertiary drugs:
AChE Quaternary drugs:
Physostigmine (Anticholinum, Ezerin)
Rivastigmine (Exelon).
Donepezil (Aricept).
Ipidacrine (Neuromidin).
Galantamine hydrobromide (Reminil,
Nivalin)
Edrophonium (tensilone)
Neostigmine (Prozerin)
Ambenonium (Oksazil)
Pyridostigmine (Kalimin)
Distigmine (Ubretide)
AChE, irreversible:
Phospholine iodide (ecothiopathy)
Ethylnitrophenylethylphosphonate (armine)
Choline alfoscerate (gliatilin, cerepro)
aminopyridine (pimadine)

13. M-cholinomimetics

Pilocarpine
Aceclidine
Amanita muscaria (fly agaric)
contains muscarine (not
enters the CNS)
tertiary amines:
ibotenic acid and
muscimol, which
act on the CNS

14. M-hmm. Local Action:

1. Cause contraction of the circular muscle
*. constriction of the pupil (miosis - from the Greek -
myosis - closing);
*. anterior chamber angle of the eye
(the root of the iris is pulled back),
permeability of the trabecular zone →
improves the outflow of aqueous humor from the eye
and ↓ intraocular pressure.
2.
cause contraction of the eyelash
(ciliary) muscles (accommodative spasm)
→ relaxes the ligament of zinn and curvature
lens → lens becomes larger
convex, and the eye is set on
near point of view (he sees poorly in the distance
- artificial myopia).

15.

INDICATIONS:
* Relief of glaucoma crisis. Instillation into the conjunctival
a bag of 1% solution: at the 1st hour - every 15 minutes, at the 2nd hour - 2
times, then - 1 time in 4 hours. → decreased intraocular
pressure by 25-26%. The beginning of the effect - after 30-40 minutes, reaches
maximum after 1.5-2 hours and lasts for 4-14 hours.
* Course treatment of glaucoma. Enter 1-2 drops of a 1% solution 3 times a day.
day, Extended Release Pilocarpine Systems
provide control of intraocular pressure for 1 day,
* Accommodative strabismus
NE:
possible fibrous degeneration of the intraocular muscles, irreversible
miosis,
posterior synechia (fusion of the iris with the lens),
increased capillary permeability (edema, hemorrhage),
dark adaptation is disturbed due to displacement of the vitreous body
(difficult to work in low light)

16. Aceclidine (Aceclidinum)

Indications:
* postoperative atony of the gastrointestinal tract and bladder, reduced
uterine tone and bleeding postpartum period;
* in ophthalmology - to lower intraocular pressure when
glaucoma.
Side effects: salivation, sweating, diarrhea.
Contraindications: angina pectoris, atherosclerosis, bronchial
asthma, epilepsy, hyperkinesis, pregnancy, gastric
bleeding.
Release form: 1 ml ampoules of 0.2% solution N. 10, ointment 3-5% in
tubes of 20 g.
Method of application: injected s / c 1-2 ml of a 0.2% solution. WFD - 0.004,
VSD - 0.012. In ophthalmology, 3-5% eye ointment is used.
Aceclidine (Aceclidinum)

17. Amanita poisoning

Signs of poisoning:
* nausea, vomiting, abdominal pain, diarrhea,
* increased sweating, salivation,
* shortness of breath, cyanosis, pupillary constriction, delirium,
* hallucinations, panic reaction, causeless laughter, inadequate
reaction to the environment
* convulsions, loss of consciousness.
First aid for fly agaric poisoning:
* Gastric lavage with clean water
* the appointment of saline laxatives (25 - 30 g of magnesium or sodium sulfate
in 2 - 3 glasses of water) and activated charcoal 1g/kg.
* Competitive antagonist – intravenous administration 0.1% solution of atropine
sulfate - 2 ml every 10 minutes (until dry mouth and
pupil dilation)
* Psychomotor agitation is eliminated by the appointment → 2.5% solution
chlorpromazine (1 - 2 ml in 20 ml of 40% glucose solution intravenously) wet
wrapping, cold on the head, oxygen therapy.

18. N-cholinomimetics (GANGLIOSTIMULATORS)

excite N-XR of carotid sinus
glomerulus → regulate
operation of the Na/K pump.
Stopping the pump during hypoxia is accompanied by
depolarization and release Ah →
exciting N-XR at the endings of the carotid
nerve, creates a stream of impulses for
reflex stimulation of the respiratory center
(along Hering's nerve) → frequency and depth
respiratory movements.

19. nicotine

A typical representative
exciting as
peripheral N-XR and
N-XR CNS, is nicotine.
The action of nicotine
biphasic:
small doses stimulate
"Nicorette" (contains
nicotine).
large oppress N-XP.
Nicotine is highly toxic
so in medical
practice is not applied, and
only lobelin is used
and cytiton.
nicotine

20. Nicotine

Isolated in 1928 from tobacco
(brought to Europe in the 16th century).
The chemical formula is described in
1843
First synthesized in 1893.
2-phase action:
excitation (I phase) N-XP
gives way to oppression
(blockade) N-XR (phase II).
Nicotine
Symptoms of acute poisoning
nicotine
*
*
*
*
*
*
salivation, nausea, vomiting,
↓ respiration, skin blanching
covers,
increased heart rate, blood pressure
general weakness, dizziness,
headache, noise in the head and ears.
impaired consciousness, possible
even convulsions and seizures
epileptic.
After excitement comes
a state of severe inhibition,
accompanied by an extension
pupils, drop in pulse,
cessation of cardiac
Emergency care for
poisoning
If breathing is disturbed, prolonged artificial
breath; in cardiac arrest intracardiac administration
adrenaline (0.5-1 ml 0.1%
solution).
When aroused, sedatives
(preparations of valerian,
bromides).
For convulsions - intramuscularly
hexenal (10 ml of 10% solution)
or barbamil (5-10 ml 5
solution)

21. chronic poisoning

Long-term tobacco use leads to
many diseases:
*Chronical bronchitis,
* BP, accelerated heart rate, damage
walls blood vessels→ chest pains,
myocardial infarction.
*may develop cancer of the lips, salivary glands,
larynx, esophagus, lungs and other organs.
*Reduces mobility in men
spermatozoa. In women during pregnancy
may cause fetal harm.
* teeth are destroyed and turn yellow, develops
chronic gastritis and peptic ulcer
stomach, osteoporosis, aging skin.
*psychic addiction → when trying
stop smoking → discomfort,
tension, inability to concentrate,
decreased mental and physical
performance, memory and sleep disorders,
restlessness, irritability, possible
uncontrollable aggression and
paranoid psychosis.
FOR CHRONIC POISONING
* conjunctivitis, loss of sensation
cornea,
* atrophic changes in mucous membranes
upper respiratory tract and gums,
ulceration,
* increased sweating, trembling,
Digestive system
* salivation, gastric hypersecretion
and other vegetative disorders,
weight loss.
The cardiovascular system
* Narrowing of blood vessels of the skin, internal
organs, blood pressure.
* work of the heart and myocardial needs
in oxygen. Arrhythmias are possible.
* adhesive ability of platelets.
vegetative disorders -
* migraine attacks,
* coronary spasm (the so-called "tobacco
angina pectoris")
chronic poisoning

22. N-cholinomimetics

N-cholinomimetics
Indications:
weakening or reflex cessation of breathing (poisoning
carbon monoxide), neonatal asphyxia.
shock, collapse (Lobelin, stimulating the center of the vagus in the oblong
brain →↓ heart rate and blood pressure. Later, BP rises due to stimulation
sympathetic ganglia and adrenal medulla.
Cytisine has only a pressor effect)
for smoking cessation
Side effects:
excitation of the vomiting center (nausea, vomiting),
slowdown heart rate, cardiac arrest,
respiratory depression,
convulsions.
Contraindications:
severe damage to the CCC
respiratory arrest due to exhaustion of the respiratory center

23. M-, N-cholinomimetics

M-, Ncholinomimetics
Acetylcholine
Carbachol (Carbachol)
0.5-1% solutions of carbacholin - in eye drops for
glaucoma treatment
Inside and in injections, the drug is never
used as a result of significant toxicity!

24. AChE funds

25. AChE funds

26. Effects of exposure to AChE drugs on organs with M-cholinergic receptors

Peripheral effects:
* miosis
* tone and motor activity (peristalsis) of the gastrointestinal tract,
* bronchial tone (causes bronchospasm), as well as tone and
contractile activity of the ureters.
* secretory activity of the external secretion glands (salivary,
bronchial, intestinal, sweat
* ↓ HR and tend to ↓BP
*
overdose of drugs from the group of M-cholinergic blockers
Central:
* Improved cognitive function - slow down the formation of amyloid
plaques, which are one of the main pathological signs disease
Alzheimer's.
*Improve neuromuscular transmission: residual effects after
poliomyelitis, paralysis, neuritis, trauma

27. karbofos, chlorophos, metaphos, thiophos Poisonous substances: Sarin, Soman, Tabun, Phosphorylthiocholines

28. Signs of poisoning with AChE substances

Muscarinic
effects
1) spasm of the pupil (miosis);
2) the strongest 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
tightness behind the sternum, shortness of breath);
5) profuse sweating → skin
wet, cold, sticky.
6) From the side of the heart can
both tachycardia and
(more often) bradycardia.
Nicotine Effects
Manifest
*
*
*
hyperkinesis,
muscle twitches
fibers, contractions
individual muscle groups→
development of clonic and
tonic convulsions,
general weakness
mental
violations
Death occurs as a result of failure
respiration, bronchospasm and pulmonary edema

29. Treatment of FOS poisoning

*
remove FOS from the skin and mucous membranes → wash off with a 3-5% solution
SODIUM HYDROCARBONATE or simply soap and water.
* If substances are ingested, gastric lavage is necessary
* If FOS got into the blood → excretion in the urine (forced
diuresis) + HEMOSORPTION (artificial kidney)
MEDICAL THERAPY:
* overexcitation of M-cholinergic receptors → the use of high doses of Mholinoblockers: administered intravenously, 2-4 ml of a 0.1% solution, with
interval of 5-10 min. Criteria for the sufficiency of the dose of atropine sulfate
is the appearance of tachycardia, dilated pupils, dry mouth
* Specific antidotes - acetylcholinesterase reactivators:
dipyroxime (The average dose is 3-4 ml of 15% solution), aloxime,
isonitrosine
interact with FOS residues associated with
acetylcholinesterase, releasing the enzyme.
the action of cholinesterase reactivators develops insufficiently
quickly → the use of AChE reactivators in conjunction with Mholinoblockers.

N-cholinomimetic agents. Use of nicotinomimetics for tobacco control.
Localization of Hn-cholinergic receptors and pharmacological effects when they are stimulated.
Localization: ANS neuronal ganglia, adrenal medulla, CNS neurons
Pharmacological effects when stimulated:
1) excitation of the neuronal ganglia of the ANS (sympathetic stronger than parasympathetic)
2) CCC: tachycardia, vasospasm, hypertension
3) Gastrointestinal tract, MPS: the predominance of parasympathetic effects (vomiting, diarrhea, frequent urination)

5) CNS: psychostimulation (at low doses of agonists), vomiting, tremor, convulsions, coma (at high doses of agonists)
drugs from the group of N-cholinomimetics.
Nicotine, cytisine, anabasine hydrochloride
Classification of Hn-cholinergic blockers. Indicate the place of their action on the PNS diagram.
but) short action- trepyrium iodide (hygronium);
b) medium duration actions - hexamethonium benzosulfonate (benzohexonium), azamethonium bromide (pentamine);
in) long-acting- pempidine (pyrilene).
Site of action on the PNS diagram: ANS ganglia, adrenal medulla, CNS.
mechanisms of action and pharmacological effects of N-cholinomimetics.
Mechanism of action: excitation N-Chr. Initial action - stimulation of H-Chr, long-term action - depolarization block.
Pharmacological effects of N-cholinomimetics:
1) stimulation of autonomic ganglia (sympathetic is stronger than parasympathetic)
2) cardiovascular system:
- tachycardia
- peripheral and coronary vasospasm
- hypertension
3) Gastrointestinal tract, urinary system: inhibition of activity
4) chemocarotid zone: stimulation of respiration
5) CNS: low doses: psychostimulation, high doses - vomiting, tremor, convulsions, coma.
side effects of N-cholinomimetics.
1) nausea, vomiting, dizziness, headache
2) diarrhea, hypersalivation
3) tachycardia, increased blood pressure, shortness of breath, turning into respiratory depression
4) mydriasis, followed by miosis
5) muscle cramps
6) visual and hearing disorders
main indications and contraindications for the use of N-cholinomimetics.
Indications:
ü Facilitate smoking cessation
ü reflex respiratory arrest (during operations, injuries, etc.)
ü shock and collaptoid states (pressor effect), respiratory and circulatory depression in patients with infectious diseases.
Contraindications:
ü atherosclerosis
a marked increase in blood pressure
ü erosive and ulcerative lesions of the gastrointestinal tract in the acute phase, bleeding from large vessels
o pulmonary edema
o pregnancy.
LOBELIN (Lobelinum).
The alkaloid contained in the plant Lobelia inflata, fam. bellflowers (Campanulaceae).
The lobelin racemate is obtained synthetically.
In medical practice, Lobelin hydrochloride (Lobelini hydrochloridum) is used. l-1-Methyl-2-benzoylmethyl-6-(2-hydroxy-2-phenylethyl)-piperidine hydrochloride.
Synonyms: Antisol, Atmulatin, Bantron, Lobatox, Lobelinum hydrochloricum, Lobeton, Lobidan, etc.
Lobelin is a substance that has a specific stimulating effect on the ganglia of the autonomic nervous system and carotid glomeruli (see also Ganglion blocking drugs).
This action of lobelin is accompanied by excitation of the respiratory and other centers medulla oblongata. In connection with the excitation of respiration, lobeline was proposed as an analeptic for use in reflex respiratory arrest (mainly when inhaling irritants, carbon monoxide poisoning, etc.).
In connection with the simultaneous excitation of the vagus nerve, lobelin causes a slowing of the heartbeat and a decrease in blood pressure. Later, blood pressure may increase slightly, which depends on vasoconstriction due to the stimulating effect of lobelin on the sympathetic ganglia and adrenal glands. In large doses, lobelin excites the vomiting center, causes deep respiratory depression, tonic-clonic convulsions, and cardiac arrest.
Recently, lobeline as a respiratory stimulant is used extremely rarely. With a weakening or cessation of breathing, developing as a result of progressive depletion of the respiratory center, the introduction of lobeline is not indicated.
Apply lobelin in the form of injections intravenously, less often intramuscularly.
Intravenously, lobeline is administered slowly (1 ml over 1 to 2 minutes). With rapid administration, temporary respiratory arrest (apnea) sometimes occurs and side effects from the cardiovascular system (bradycardia, impaired conduction) develop.
Lobelin is contraindicated in acute organic diseases of cardio-vascular system.
Lobelin and others similar to him in action<<ганглионарные>> Substances (cytisine, anabasine) have been used in recent years as aids in smoking cessation. Tablets containing lobelin are available for this purpose under the name<<Лобесил>> (Tabulttae "Lobesilum").
The tablets are coated (acetylphthalylcellulose), which ensures the passage of the drug unchanged through the stomach and its rapid release in the intestine.
The use of tablets<<Лобесил>>, as well as tablets and other drugs containing cytisine and anabasine hydrochloride, reduces the desire to smoke and alleviates the painful phenomena for smokers associated with smoking cessation.
The mechanism of action of these drugs is apparently associated with competitive relationships in the area of ​​the same receptors and biochemical substrates with which nicotine interacts in the body, which is also<<ганглионарным>> means.
Quitting smoking requires more than just pills<<Лобесил>>, but at the same time the smoker's firm decision to stop smoking.
After stopping smoking, take 1 tablet 4-5 times a day for 7-10 days. Subsequently, if necessary, you can continue taking the tablets for 2 to 4 weeks with a gradual decrease in the frequency of administration. With relapses, the course of treatment can be repeated.
The use of tablets with lobelin, cytisine and anabasine is contraindicated in case of exacerbation of peptic ulcer of the stomach and duodenum, sudden organic changes in cardiovascular system. Treatment should be carried out under medical supervision. In case of an overdose, side effects are possible: weakness, irritability, dizziness, nausea, vomiting.
CYTIZINE (Cytisinum).
Cytisine is an alkaloid found in the seeds of the broom plant (Cytisus laburnum L.) and the lanceolate thermopsis (Thermopsis lanceolata, R. Br.), both from the legume family (Leguminosae).
related to substances<<ганглионарного>> action and in connection with the stimulating effect on breathing is considered as a respiratory analeptic. For this purpose, it is produced in the form of ready-made 0.15% aqueous solution entitled<<Цититон>> (Cytitonum).
In recent years, cytisine has also been used as a smoking cessation aid (see tablets<<Лобесил>>) .
Cytisine has a stimulating effect on the ganglia of the autonomic nervous system and related formations: the chromaffin tissue of the adrenal glands and carotid glomeruli.
Characteristic for the action of cytisine (as well as lobelin) is the excitation of respiration associated with reflex stimulation of the respiratory center by enhanced impulses coming from the carotid glomeruli. Simultaneous excitation of the sympathetic nodes and adrenal glands leads to an increase in blood pressure.
The effect of cytiton (cytisine solution) on respiration is short-lived.<<толчкообразный>> nature, however, in some cases, especially with reflex respiratory arrest, the use of cytiton can lead to a stable restoration of breathing and blood circulation.
Previously, cytiton was widely used for poisoning (with morphine, barbiturates, carbon monoxide, etc.). Due to the emergence of specific antagonists of opiates (naloxone, etc.) and barbiturates (bemegride) and the short duration of action, cytiton and lobelin are currently of limited use. Nevertheless, with reflex respiratory arrest (during operations, injuries, etc.), cytiton can be used as a respiratory analeptic; due to the pressor effect (which distinguishes it from lobelin), cytiton can be used in shock and collaptoid conditions, in respiratory and circulatory depression in patients with infectious diseases, etc.
Cytiton is injected into a vein or intramuscularly. The most effective intravenous administration. If indicated, the injection of Cytiton can be repeated after 15-30 minutes.
Cytiton was previously also used to determine blood flow velocity. The method consists in establishing the time that elapses from the moment cytiton is introduced into the cubital vein until the first deep breath appears. The definition is more demonstrative than with the introduction of lobelin, since the excitation of respiration is more pronounced and the change in respiration is easy to register. Usually administered for this purpose 0.7 - 1 ml of cytiton (0.015 ml per 1 kg of patient's body weight).
Cytiton is contraindicated (because of its ability to increase blood pressure) with severe atherosclerosis and hypertension, bleeding from large vessels, pulmonary edema.
Cytisine (0.0015 g = 1.5 mg) is included in the tablets<<Табекс>> (Tabex, Bulgaria), used to facilitate smoking cessation. The mechanism of action of the drug is similar to the mechanism of action of lobeline and anabazine.
The use of tablets<<Табекс>> should be done as prescribed and under the supervision of a physician. In case of an overdose, nausea, vomiting, dilated pupils, increased heart rate are possible, which requires discontinuation of the drug.
There are also films with cytisine (Membranulae cum Cytisino). Oval-shaped polymer plates with blunt edges, white or with a yellowish tint (9 X 4.5 X 0.5 mm), contain 0.0015 g of cytisine. The film is glued to the gum or mucous membrane of the buccal region daily for the first 3-5 days 4-8 times.
With a positive effect, treatment is continued according to the following scheme: from the 5th to the 8th day, 1 film 3 times a day, from the 9th to the 12th day, 1 film 2 times a day, from the 13th to the 15th day 1 film 1 time per day. From the first day of treatment, you should stop smoking or sharply reduce the frequency of smoking.
In the first days of using the film with cytisine, unpleasant taste sensations, nausea, mild headache, dizziness, and a slight increase in blood pressure are possible. In these cases, you should stop taking the drug.
The use of films with cytisine is contraindicated in bleeding, severe hypertension, advanced stages of atherosclerosis.
ANABASINA HYDROCHLORIDE (Anabasinum hydrochloridum).
Anabasine is an alkaloid found in the plant Anabasis aphylla L. (leafless barnyard), fam. haze (Chenopodiaceae).
Chemically, it is 3-(piperidyl-2) pyridine.
By pharmacological properties close to nicotine, cytisine and lobelin.
In small doses, anabasine hydrochloride has been proposed as a means of facilitating smoking cessation.
For this purpose, the drug is available in the form of tablets, films and chewing gum.<<Гамибазин>> .
Apply tablets with anabasine hydrochloride orally or under the tongue daily. From the first day of taking the tablets, it is necessary to stop smoking or drastically reduce its frequency and completely stop smoking no later than 8-10 days from the start of treatment.
If the craving for smoking does not decrease within 8-10 days, stop taking the tablets and make a new attempt at treatment after 2-3 months.
Tablets are contraindicated in atherosclerosis, marked increase in blood pressure, bleeding.
In the first days of taking the tablets, nausea, headache, and an increase in blood pressure are possible. Usually these phenomena disappear when the dose is reduced. If necessary, stop taking the tablets.
There are indications that the use of anabasine (in the form of tablets orally or sublingually) can cause toxicoderma.
Films with anabasine hydrochloride (Membranulae cum Anabasino hydrochloridi). Oval-shaped polymer plates of white (or with yellowish tints) color, 9 X 4.5 X 0.5 mm in size, containing 0.0015 g (1.5 mg) of anabasine hydrochloride. They are also designed for smoking cessation.
The film is glued to the gums of the labial part or the mucous membrane of the buccal region daily for the first 3-5 days 4-8 times.
From the first day of treatment, it is advisable to stop smoking or drastically reduce the frequency of smoking.
In the first days of using the film with anabasine hydrochloride, unpleasant taste sensations, nausea, mild headache, dizziness, and a slight increase in blood pressure are possible. In these cases, the drug should be discontinued.
Gamibasin (Gamibasin). Chewing gum(based on a special chewing mass) containing 0.003 g of anabazine hydrochloride.
Rubber band rectangular or square shape(22 X 22 X 8 mm, or 32 X 22 X 5 mm, or 70 X 19 X 1 mm) of light gray or light yellow color with the smell of food aromatic substances (with the addition of sugar, molasses, citric acid, flavoring, etc. .).
Is one of dosage forms anabasine for smoking cessation. Applied by prolonged chewing daily at first 1 gum (0.003 g) 4 times a day for 4 to 5 days. With a positive effect, the treatment is continued according to the following scheme: from the 5th - 6th to the 8th day - 1 gum 3 times a day; from the 9th to the 12th day - 1 gum 2 times a day; in the future until the 20th day - 1 gum 1 - 2 times a day. In the future, it is possible to conduct repeated courses.