Prokinetics- a group of drugs that regulate motor function digestive tract. Drugs with a prokinetic effect improve the movement of intestinal contents through the digestive tract, promote better functioning of the sphincter between the stomach and esophagus, and prevent the reflux of food from the stomach into the esophagus.

In Russia, the pharmacy market is represented by three prokinetics approved for use: Metoclopramide, Domperidone, Itopride. Other drugs are banned or are in development.

There are several pharmacological groups of prokinetics.

Dopaminergic D2 receptor blockers

They are the most studied and widely used group of prokinetics. Drugs in this group, by blocking dopamine D2 receptors, regulate motor activity digestive tract by increasing the tone of smooth muscle cells in the intestines and stomach. They have antiemetic and antihiccup effects.

Serotonin 5-HT4 receptor agonists

Drugs of this group, acting on serotonin H4 receptors in the submucosal layer of the digestive tract, stimulate the release of acetylcholine. Acetylcholine increases the motor activity of the stomach and intestines. Studies have revealed the ability of these drugs to reduce abdominal discomfort and normalize stool in irritable bowel syndrome. At this stage, active trials of drugs from this group are underway as a promising direction in treatment.

Serotonin H3 receptor antagonists

The research of this pharmaceutical group began after the discovery of the properties of Metoclopramide to inhibit the functioning of serotonin H3 receptors and the advancement of the theory that part of its prokinetic properties are associated specifically with serotonin and its receptors. The synthesis of drugs that would selectively act only on H3 receptors began.

• (Latran, Zofran). The drug accelerates the movement of food from the stomach into the duodenum and normalizes tone. Used in the treatment of nausea and vomiting caused by chemotherapy in cancer patients or anesthesia. It has not found widespread use in the treatment of gastroesophageal reflux disease and irritable bowel syndrome.
• Tropindole (Tropisetron, Navobane). The first drug from this group that can long time normalize the functioning of the lower esophageal sphincter, preventing the reflux of gastric contents. Has a pronounced antiemetic effect. Used in cancer patients after chemotherapy.

New generation prokinetics with dual action

• Itopride (Ganaton, Itomed). The drug simultaneously affects dopamine D2 receptors and anticholinesterase receptors, which expands the scope of its application. It has a positive effect on the tone of the lower esophageal sphincter, preventing the reflux of gastric contents into the esophagus. At the same time, it stimulates peristalsis of all parts of the intestine, improving bowel movements during constipation. Has a moderate antiemetic effect. Does not affect the secretory activity of the stomach. Does not affect the structures of the central nervous system. In the treatment of gastroesophageal reflux disease it has proven to be better than Domperidone. The advantages of Itopride include the absence of interaction with other drugs.

The choice of prokinetic agent is based on clinical effectiveness in the treatment of different parts of the digestive tract, safety and contraindications.

Of all the listed drugs, only 2 drugs meet the effectiveness/safety conditions - Itopride and Domperidone. In the treatment of motor activity disorders of the upper gastrointestinal tract (esophagus, stomach), the drug of choice is Itopride.

Indications for use

Contraindications

• gastrointestinal bleeding;
• gastric perforation;
• pregnancy;
• mechanical obstruction of the gastrointestinal tract;
• prolactinoma (for Domperidone).

Natural prokinetics

• Iberogast. Herbal preparation based on extracts of 9 plants. The mechanism of action is associated with the individual effect of each plant on the digestive tract. The main point of application is the stomach. Strengthens the passage of food from the stomach, normalizes motility. Reduces the production of hydrochloric acid and increases the production of mucus in the stomach.

It differs from “chemical prokinetics” in its effectiveness combined with a high safety profile. Used in the treatment of functional dyspepsia.

Chemical transmission of excitation in the ganglia occurs with the help of the mediator acetylcholine, secreted by the endings of preganglionic neurons. Ganglion neurons are also excited by nicotine, so their transmitter receptor is called H-cholinergic receptor. In addition to the ganglia, H-cholinergic receptors are present in neurons of various brain formations, in the carotid glomerulus, adrenal medulla and skeletal muscles Oh.

NCRs are stimulated by acetylcholine, nicotine, and lobeline. Lobelin And cytisine excite the NCR of the carotid glomerulus, this leads to reflex excitation respiratory center.

Nicotine has a two-phase effect: first it excites and then paralyzes the receptors.

DRUGS BLOCKING AUTONOMIC GANGLIA (pachycarpine, pentamin, benzohexonium, hygronium, temequin)

Ganglioblockers are drugs that can inhibit or completely stop the transmission of excitation in the ganglia of the sympathetic and parasympathetic nervous system. They inhibit the NCR of the adrenal medulla, reducing the production of adrenaline. Ganglion blockers inhibit the NChR of the carotid glomeruli, reducing their stimulating effect on the respiratory center.

Under the influence of ganglion blockers, vasodilation occurs, leading to a decrease in blood pressure, which is associated with a decrease in the flow of vasoconstrictor impulses from the vasomotor centers to arterial vessels through the ganglia of the sympathetic system. Decreasing the production of adrenaline and other vasoconstrictors is an additional mechanism for lowering blood pressure. When taking ganglion blockers, patients should lie down. When they quickly move to a vertical position, it occurs orthostatic collapse, which is caused by a sharp decrease in blood pressure and the inability to transmit the regulatory influence of the central nervous system through the ganglia to the executive organs of the circulatory apparatus - the heart, blood vessels. Used to lower blood pressure, to relieve hypertensive crisis. For controlled hypotension (short-term reduction normal pressure during operations) short-acting drugs are used, for example, hygronium.

Ganglion blockers, inhibiting the conduction of impulses in the ganglia of the parasympathetic system, cause a decrease in the secretion of the digestive glands, relaxation of smooth muscle spasms, bile ducts, intestines, ureters. As a result, they are used for diseases of the gastrointestinal tract. Glaucoma is a contraindication to the use of ganglion blockers, since these drugs cause pupil dilation.

Pahikarpin

MUSCLE RELAXANTS

Muscle relaxants reduce muscle tone due to the blockade of NChR on the postsynaptic membrane of skeletal muscles and the resulting blockade of the transmission of excitation from motor nerves to muscles. The muscles of the neck, pharynx, esophagus, then the limbs and, lastly, the muscles of the diaphragm and intercostal muscles are most sensitive to them, which can lead to respiratory arrest. Therefore, just in case, when using muscle relaxants, it is necessary to have an artificial respiration apparatus.

Used for surgical operations to relax muscles, for insertion of gastroscopes, bronchoscopes, and for convulsions that cannot be controlled by drugs of other groups.

1. Anti (tubocurarine, diplacin, arduan).

2. Depolarizing muscle relaxants (ditilin).

It is also possible to distinguish drugs with a mixed mechanism of action.

The competitive type of action blocks the NChR of the postsynaptic membrane of skeletal muscles and, thus, makes it impossible for the transmitter acetylcholine to connect with them. Due to this, there is no excitation of the NCR and subsequent depolarization of the muscle cell membrane, which is equivalent to the absence of cell excitation. With an increase in the concentration of acetylcholine, it is able to displace the blocker from the connection with the receptor and, thus, be its antagonist. To increase acetylcholine levels, anticholinesterase agents are administered ( prozerin).

Depolarizing muscle relaxants have a cholinomimetic effect on the postsynaptic membrane, but, unlike the mediator acetylcholine, they cause persistent depolarization, preventing the membrane from returning to its normal initial state (repolarizing). In this case, the conduction of impulses from the nerve to the muscle is inhibited due to overexcitation of the NCR.

Muscle relaxants with a depolarizing effect are destroyed by cholinesterase, so in case of an overdose, fresh citrated blood, which contains pseudocholinesterase, is injected. Anticholinesterase drugs enhance the effect of depolarizing muscle relaxants due to the accumulation of acetylcholine, so proserin should not be used in this case.

CHOLINERGICS

Sympathetic nerves emerge from the thoracolumbar region spinal cord. Preganglionic fibers of the parasympathetic nervous system exit the central nervous system as part of the cranial nerves (especially III, VII, IX and X), as well as the third and fourth sacral spinal roots. The preganglionic fibers of the parasympathetic nerves are much longer than those of the sympathetic nerves, since the ganglia of the parasympathetic nerves are often located in the internal organs themselves.

In the human autonomic nervous system there are synapses with chemical transmission. The features and mechanisms of this transmission are, in principle, the same as in the neuromuscular system, however, in the autonomic nervous system, pre- and postsynaptic transformations are much more diverse. Synapses of the sympathetic nervous system are located either in the paravertebral or prevertebral ganglia and nerve plexuses located in abdominal cavity. Postganglionic unmyelinated nerve fibers innervate most internal organs.

Today there are more than a dozen types in the autonomic nervous system nerve cells, producing various mediators - acetylcholine, norepinephrine, serotonin, etc.

CHOLINERGICS

Acetylcholine synthesized in nerve endings from choline and acetyl-coenzyme A under the influence of the enzyme choline acetyltransferase both in the body of the neuron (from which it then descends to the axon terminal) and in the endings of nerve fibers. Choline is taken up by nerve endings from the extracellular fluid using a special choline transporter localized on the terminal membrane.

Acetylcholine is deposited in nerve endings in the cytoplasm and in synaptic vesicles in complex with ATP or neuropeptides.

Influenced nerve impulse they contain Ca 2+, which causes the vesicles to move towards inner surface presynaptic ending. In this case, within 1 millisecond, several hundred portions (quanta) of acetylcholine contained in them are released from the vesicles into the synaptic cleft. This process, called acetylcholine quantal release, is sensitive to changes in extracellular Ca 2+ concentration. Divalent ions Mg 2+, Co 2+ and Mn 2+, being antagonists of Ca 2+, inhibit the transmission of excitation in the cholinergic synapse. Acetylcholine diffuses into the synaptic cleft and binds to its receptors located on the surface of the postsynaptic membrane. The reversible binding of acetylcholine to receptors leads to the opening of cation channels on the postsynaptic membrane, causing a current of Na + and, to a lesser extent, K + . The resulting depolarization (local synaptic potential) spreads throughout the cell membrane, and, having reached a certain value, leads to the generation of an action potential and causes corresponding changes in the function of the effector organ.

Quick removal acetylcholine from the cholinergic receptor produces a specific enzyme acetylcholinesterase, located on the membrane next to the cholinergic receptor, which hydrolyzes acetylcholine into choline and acetate. Choline is actively captured by the presynaptic terminal and transported inside it (excess acetylcholine or choline in the synaptic cleft inhibits this process), where, with the participation of acetylcoenzyme A of mitochondria and choline acetylase, it is again converted into acetylcholine. Acetate enters the lymph and then into the bloodstream.

Excess acetylcholine that enters the bloodstream is hydrolyzed by butyrylcholinesterase, which inactivates not only acetylcholine, but also other choline esters and some drugs (novocaine).

Today it is believed that acetylcholine (ACh) is released in the endings:

1) all preganglionic fibers (sympathetic and parasympathetic);

2) all postganglionic parasympathetic fibers (as a result of this the parasympathetic nervous system was called cholinergic);

3) some postganglionic sympathetic fibers (innervating the sweat glands and causing vasodilation in skeletal muscles);

4) nerves innervating the adrenal medulla;

5) somatic nerves innervating skeletal muscles;

6) some neurons of the central nervous system.

At presynaptic terminals there are receptors that respond to acetylcholine; the excitation of some of them promotes the further release of acetylcholine, while the excitation of others inhibits this process.

Cholinergic receptors of the membrane of the effector organ (smooth muscle cells, automatically functioning P-cells of the myocardium, AV node, exocrine glands innervated by postganglionic steam sympathetic nerves, as well as on the membranes of smooth muscle cells of the stomach, uterus, sweat glands, innervated by some postganglionic sympathetic nerves) react with excitement to the fly agaric poison - muscarine, hence their name M-cholinergic receptors.

Cholinergic receptors of the postsynaptic membrane of neurons of the autonomic ganglia, ganglion-like formations (adrenal medulla, carotid glomeruli, neurohypophysis) can be selectively blocked by the introduction of hexamethonium; cholinergic receptors of the postsynaptic membrane of skeletal muscles are not inhibited by hexamethonium, but are blocked by tubocurarine, thus, cholinergic receptors in the ganglia and neuromuscular synapses ah are different, although both types of these receptors do not respond to muscarine, but respond to the alkaloid nicotine contained in tobacco leaves, which is why they are called N-cholinoreceptors.

The central nervous system contains both N- and M-cholinergic receptors, but there are more of the latter.

In addition to their location in postsynaptic structures, cholinergic receptors are also localized presynaptically. Stimulation of presynaptic N-cholinergic receptors promotes the release of acetylcholine, and stimulation of M-cholinergic receptors inhibits it.

In addition to its mediator role, ACh has a general biological effect: it enhances pulmonary ventilation, contracts the muscles of the bronchi, reduces bronchial secretion, enhances the secretion of the digestive tract and gastrointestinal tract, peristalsis, but its effect is short-lived. When administered intravenously, acetylcholine causes vasodilation as it promotes the release of nitric oxide (NO) from the vascular endothelium.

Localization of M- and N-cholinergic receptors and the results of their activation

The effect of ACh can be reproduced using pharmaceuticals. Medications, which have an effect on the effector organs similar to the postganglionic parasympathetic neuron are called cholinomimetics, the opposite - cholinergic blockers.

DRUGS AFFECTING M-CHOLINORECEPTORS

1. M-cholinomimetics ().

2. M-anticholinergics (atropine sulfate, platyphylline hydrotartrate, homatropine hydrobromide, metacin, gastrocepin, aprofen, arpenal, troventol, chlorosil, fubromegan, tropicamide, cyclopentolate).

In each subgroup, substances containing pentavalent (quaternary compounds) and trivalent nitrogen (tertiary compounds) are distinguished. Quaternary compounds, unlike tertiary ones, are poorly soluble in lipids, and therefore are poorly absorbed from the gastrointestinal tract and difficult to penetrate the blood-brain barrier. Therefore, to obtain central effects, they prefer to prescribe tertiary compounds, and to obtain peripheral effects, they prefer to prescribe quaternary ones.

There are 5 variants of M-cholinergic receptors, which differ from each other in their ability to activate different signaling mechanisms: initiate the breakdown of phosphatidylinositols, inhibit adenylate cyclase, open some potassium channels (in the atria, neurons of the brain) and close others.

Activation of different M-cholinergic receptors is accompanied by unequal intracellular and membrane processes leading to changes in the function of effector organs. Moreover, in the same organ there may be several variants of M-cholinergic receptors. With the exception of perenzipine (gastrocepin), which selectively blocks M1 cholinergic receptors, clinically used agonists and antagonists of M cholinergic receptors either show little or no selectivity for the various subtypes of these receptors.

M-cholinomimetic drugs(tertiary - pilocarpine hydrochloride, aceclidine and quaternary - bethanechol, methacholine) call:

Contraction of smooth muscles of the intestines, stomach, bronchi of the uterus, ciliary muscle, iris sphincter;

Increased secretion of salivary, bronchial, sweat, gastric glands;

Slowing down the conduction of excitation in the atrioventricular node, reducing the excitability and automaticity of P-cells of the heart.

In eye practice for glaucoma to narrow the pupil and associated decrease in intraocular pressure.

Normal intraocular pressure is about 15 mmHg; when intraocular pressure increases, glaucoma develops. The balance of aqueous humor in the eye is maintained by the ciliary body by regulating the outflow of fluid through the trabecular system into Schlemm's canal. Aqueous humor enters the anterior chamber of the eye - through the pupil and flows into Schlemm's canal (venous sinus of the sclera - a circular canal in the limbus) and ultimately into the episcleral veins. The trabecular network of the angle of the anterior chamber of the eye (Fontan's spaces) is Schlemm's roof, a kind of filter through which aqueous humor enters the venous sinus.

For open-angle glaucoma due to pathological changes in the trabecular meshwork, leading to decreased outflow intraocular fluid, intraocular pressure increases to 24 mm Hg. and more. Increased intraocular pressure can cause damage to the optic nerve. Usually, increased intraocular pressure can be reduced by increasing the outflow of intraocular fluid with the help of M-cholinomimetics, such as pilocarpine.

The iris has two muscles: the orbicularis muscle, which receives parasympathetic innervation, and the radial muscle, which is innervated by sympathetic nerve fibers. M-anticholinergic blockers and a-adrenergic agonists dilate the pupil (cause mydriasis), while M-cholinomimetics and a-adrenergic blockers constrict the pupil (cause miosis).

When the M-cholinergic receptors of the orbicularis oculi muscle are stimulated, the parasympathetic effects on the muscle increase, the muscle contracts, and the pupil narrows (miosis). Thinning of the iris sphincter occurs, as a result of which the inner angle of the anterior chamber of the eye is released and the outflow of intraocular fluid through the spaces of the iridocorneal angle and the venous sinus of the sclera is facilitated. Thus, the pressure of the intraocular fluid in the anterior chamber of the eye decreases.

In addition, the MChR of the ciliary muscle is excited, it contracts, the ligament of Zinn relaxes, and the lens becomes more convex (spasm of accommodation).

Pilocarpine, being a tertiary amine, quickly diffuses through the cornea into the intraocular fluid. The drug lowers intraocular pressure by causing contraction of the ciliary muscle, which leads to tension in the scleral spur, stretching of the trabecular meshwork and increased outflow of aqueous humor from the anterior chamber of the eye.

For resorptive purposes, less toxic ones are used. aceclidine, bethanechol: to stimulate intestinal smooth muscles and Bladder with postoperative atony of these organs and with urinary retention, if there is no obstruction urethra. Very rarely used to stop attacks of tachycardia.

All M-cholinomimetics cause miosis, leading to impaired night vision and complaints of blurred vision. Spasm of accommodation, which increases myopia and causes visual impairment, usually does not bother patients with glaucoma. However, some patients find this effect difficult to tolerate.

In case of an overdose of M-cholinomimetics or poisoning with them, symptoms of sharp excitation of the parasympathetic system are observed in all organs: constriction of the pupils, salivation, diarrhea, bradycardia, decreased blood pressure, bronchospasm. Functional antagonists of M-cholinomimetics are M-cholinergic blockers ( atropine).

M-cholinergic receptor blockers(tertiary - atropine sulfate, platyphylline hydrotartrate, homatropine hydrobromide, quaternary - metacin, gastrozepine, atrovent) reduce the effect of acetylcholine released from the endings of postganglionic fibers of parasympathetic nerves on M-cholinergic receptors.

The sensitivity of various effector organs receiving parasympathetic innervation to the action of M-anticholinergics is not the same. For example, the salivary, bronchial and sweat glands are highly sensitive to the action of these drugs, and large doses of M-anticholinergic blockers are required to dilate the pupil, paralyze accommodation and eliminate the effect of n.vagus on the heart. Even higher concentrations of drugs are necessary to reduce the parasympathetic effect on the tone of the smooth muscles of the intestine and bladder. The secretion of hydrochloric acid in the stomach is most resistant to the action of M-anticholinergics.

By weakening the influence of the parasympathetic system on organs, M-anticholinergics indirectly enhance the effect of the sympathetic nervous system on them: they increase the work of the heart - they are used for bradycardia, blockade of impulse conduction; relax the bladder, smooth muscles of the intestines, bile ducts - used for spasms of smooth muscles; reduce sweating, gland secretion - used for hypersolivation; dilate the bronchi - used for bronchospasm; dilate the pupil (mydriasis) - used to examine the fundus; cause paralysis of accommodation - used when selecting glasses.

Atropine and scopalamine are widely used:

In anesthesiology to reduce the inhibitory effect of the vagus nerve on the heart and to suppress the secretion of the bronchial glands;

To suppress spasm of smooth muscles of the intestines, biliary tract, ureters, bladder (platifillin, metacin);

To eliminate bradyarrhythmia (atropine);

To prevent the manifestations of motion sickness (scopolamine);

To reduce gastric secretion in case of gastric ulcer and duodenum, at hyperacid gastritis(pirenzepine);

For parkinsonism (cyclodol);

To eliminate bronchospasm (Atrovent).

M-anticholinergics cause relaxation of the ciliary muscle (cycloplegia), as a result of which the tension of the zinc ligament increases, the curvature of the lens decreases and paralysis of accommodation develops. The eye is set to far vision.

To examine the fundus of the eye, it is necessary to dilate the pupil - mydriasis. For ophthalmoscopy, short-acting M-anticholinergic blockers are mainly used, for example, tropicamide And cyclopentolate, which cause mydriasis and cycloplegia (Fig. 3).

Atropine (an alkaloid found in plants such as belladonna (Atropa belladonna), henbane, datura) is a weak stimulant of the central nervous system, especially the n.vagus center; when used in small doses it can cause bradycardia, and in high doses it can cause tachycardia. Scopalamine has a sedative effect and often causes drowsiness and amnesia.

At toxic doses, both drugs cause agitation, anxiety, hallucinations, and coma. In addition, an overdose may cause tachycardia, dilated pupils, dry mouth, fever, and psychosis. Death can occur from respiratory arrest. To weaken the effect, anticholinesterase drugs are prescribed ( prozerin).

DRUGS AFFECTING M- AND N-CHOLINORECEPTORS

I. Direct acting drugs

1. (M, N-cholinomimetics)

a) directly excitatory receptors ( acetylcholine, carbacholine)

b) presynaptic action ( cisapril, aminopyridine)

1. (M, N-anticholinergics) (amizil, norakin, tropacin, dynesin)

II. Indirect acting drugs - A anticholinesterase agents ( proserine, galantamine hydrobromide, physostigmine salicylate, armine, oxazyl, tacrine, pyridostigmine bromide, quinotiline, distigmine bromide).

Carbacholine is a quaternary ammonium compound, so it does not penetrate the blood-brain barrier. The drug is not hydrolyzed by acetylcholinesterase, as a result of which it has a longer action than acetylcholine. Sometimes M,N-cholinomimetics are prescribed for atony of the stomach, intestines or bladder, and very rarely for atrial arrhythmias.

Medicines presynaptic action inhibits the release of acetylcholine from presynaptic terminals. Botulinum toxin, produced by the anaerobic bacillus Clostridium botulinium, is an extremely potent exotoxin. Botulinum toxin type A is used in the treatment of certain types of dystonia, such as blepharospasm and strobism. In these diseases, small doses of a toxin are injected into the affected muscle to cause paralysis, lasting about 12 weeks.

M, N-anticholinergics ( amizil, norakin, tropacin, dynesin) predominantly block cholinergic receptors in the central nervous system. They are used as tranquilizers (Amizil) or antiparkinsonian drugs.

Anticholinesterase drugs(quaternary - prozerin and tertiary - galantamine hydrobromide, physostigmine salicylate, armin) – indirect cholinomimetics.

Acetylcholine binds to the active centers (anionic and esterase) of acetylcholinesterase and is first hydrolyzed to free choline and acetylated enzyme, then the covalent acetyl-enzyme bond breaks down. Carbamine esters (proserine, pyridostigmine) undergo the same two-step breakdown as acetylcholine, but the destruction of the carbamyl-enzyme bond occurs much more slowly (from 30 minutes to 6 hours). Organophosphorus compounds (armin) cause phosphorylation of the active (esterase) center of the enzyme. The covalent phosphorus-enzyme bond is very stable and cholinesterase remains inactive for hundreds of hours, therefore organophosphorus compounds are classified as irreversible cholinesterase inhibitors.

Anticholinesterase drugs lead to the accumulation of acetylcholine in the synaptic cleft and thereby enhance the effect of the latter on M- and H-cholinergic receptors. In addition, these drugs can sensitize cholinergic receptors to acetylcholine. Therefore, anticholinesterase drugs have more wide range actions than direct M-cholinomimetics, since they cause increased nerve transmission also in the ganglia of the autonomic nervous system and in the central nervous system. In addition, they stimulate the transmission of excitation from motor nerves to skeletal muscles and are used for myasthenia gravis and to eliminate the effect of muscle relaxants with an antidepolarizing mechanism of action.

The cholinergic receptors at the neuromuscular junction consist of four different protein subunits (b, g, d and two a), located in the membrane in such a way that they surround the ion channel through which cations (mainly Na +) pass. Acetylcholine molecules bind to two a-subunits, causing their conformational changes, resulting in the opening of the channel for 1 millisecond.

Armin and other substances that irreversibly inhibit cholinesterase, constrict the pupil and are used for glaucoma. However, the use of irreversible anticholinesterase drugs increases the risk of cataracts.

Physostigmine because of its local irritating effect Rarely used for glaucoma.

Galantamine, physostigmine And prozerin used for atony of the intestines, stomach and bladder, for myasthenia gravis and poliomyelitis, to eliminate the effect of muscle relaxants with an antidepolarizing mechanism of action, and sometimes to eliminate tachyarrhythmias.

Myasthenia is autoimmune disease, in which neuromuscular transmission is disrupted, since circulating antibodies (IgG) lead to a decrease in the number of functioning cholinergic receptors in skeletal muscles. The main treatments for myasthenia gravis are cholinesterase inhibitors, which increase the content of acetylcholine in the synaptic cleft.

In toxic doses, cholinesterase inhibitors initially cause symptoms of excessive stimulation of M-cholinergic receptors: salivation, sweating, constriction of the bronchi, increased content of bronchial glands, vomiting, diarrhea, frequent urination, nausea, salivation, constriction of the pupil. If the medicine is lipophilic (physostigmine, organophosphorus compounds), then convulsions, coma and respiratory arrest may occur. To eliminate these phenomena, atropine or cholinesterase reactivators (dipyroxime, paldom, isonitrosine), which bind to anticholinesterase drugs and detach them from cholinesterase, restoring its activity. When used, the process of acetylcholine hydrolysis is restored.

DRUGS ACTING ON N-CHOLINORECEPTORS

I. N-cholinomimetics (cititone, lobeline hydrochloride)

II. N-anticholinergics

1. Drugs that block autonomic ganglia (ganglion blockers) (pachycarpine, pentamin, benzohexonium, hygronium, temekhin, arfonad, quateron, imekhin)

2. Curare-like drugs (muscle relaxants)

According to the mechanism of action, they are divided into two groups:

A) anti-depolarizing muscle relaxants (tubocurarine, diplacin, arduan, pancuronium bromide, pipecuronium bromide, qualidil, melliktin, gallamin, rocuronium).

b) depolarizing muscle relaxants (ditilin).

You can also highlight c) drugs with a mixed mechanism of action.

N-cholinomimetics

Lobelin And cytisine when administered intravenously, they excite H-cholinergic receptors in the adrenal medulla, autonomic ganglia and carotid glomeruli. Stimulation of the ganglia leads to an increase in the release of mediators from the endings of postganglionic fibers of the autonomic, mainly sympathetic, ganglia, thereby increasing peripheral vascular resistance, arterial and venous pressure. This is also facilitated by catecholamines, which are more intensively released from the adrenal medulla. Stimulation of the carotid glomeruli leads to reflex excitation of the respiratory center.

Preparations containing lobeline (Lobesil) and cytisine (Tabex), as well as anabasine, are used to eliminate withdrawal symptoms that occur when quitting smoking.

Nicotine leads to activation of the sympathetic and parasympathetic ganglia, the adrenal medulla, dysfunction of the central nervous system, has a two-phase effect: first excites and then paralyzes the receptors.

Ganglioblockers(tertiary - pachycarpine, pyrylene, quaternary - pentamine, benzohexonium, hygronium, temequin) are drugs that can inhibit or completely stop the transmission of excitation in the ganglia of the sympathetic and parasympathetic nervous system (Fig. 4). They block the NChR of the adrenal medulla, reducing the production of adrenaline, and block the NChR of the carotid glomeruli, reducing their stimulating effect on the respiratory center.

Under the influence of ganglion blockers, vasodilation occurs, leading to a decrease in blood pressure, which is associated with a decrease in the flow of vasoconstrictor impulses from the vasomotor centers to the arterial vessels through the ganglia of the sympathetic system. Decreasing the production of adrenaline and other vasoconstrictors is an additional mechanism for lowering blood pressure. When taking ganglion blockers, patients should lie down. With their rapid transition to a vertical position, orthostatic collapse occurs, which is caused by a sharp decrease in blood pressure and the inability to transmit the regulatory influence of the central nervous system through the ganglia to the executive organs of the circulatory apparatus - the heart and blood vessels. They are used to lower blood pressure, to relieve hypertensive crisis, cerebral edema, left ventricular failure, and acute heart failure. Improving microcirculation in tissues is used in the treatment of patients with various forms of shock, infectious toxicosis, burn disease, and pneumonia. For controlled hypotension (short-term decrease in normal pressure during operations), short-acting drugs are used ( hygronium, arfonade (trimetaphane)).

Ganglion blockers, inhibiting the conduction of impulses in the ganglia of the parasympathetic system, cause a decrease in the secretion of the digestive glands, relaxation of spasms of smooth muscles, bile ducts, intestines, ureters, reduce the influence of the vagus nerve on the tone of the smooth muscles of the bronchi and the secretion of the bronchial glands. As a result, they are used for diseases of the gastrointestinal tract, in the treatment of chronic bronchitis, and for the prevention of attacks of bronchial asthma. Glaucoma is a contraindication to the use of ganglion blockers, since these drugs cause pupil dilation.

Pahikarpin has the ability to stimulate uterine contractions, which must be taken into account when prescribing drugs to pregnant women.

MIORELAXANTS reduce muscle tone due to the blockade of NChR on the postsynaptic membrane of skeletal muscles and the resulting blockade of the transmission of excitation from motor nerves to muscles. The muscles of the neck, pharynx, esophagus, then the limbs and, lastly, the muscles of the diaphragm and intercostal muscles are most sensitive to them, which can lead to respiratory arrest. Therefore, just in case, when using muscle relaxants, it is necessary to have an artificial respiration apparatus.

Used in anesthesiology to relax skeletal muscles, to perform surgical operations to relax muscles, to insert gastroscopes, bronchoscopes, to reduce dislocations, to reposition bone fragments, for convulsions that cannot be controlled by drugs of other groups, to prevent muscle contractions during electroconvulsive therapy.

Most muscle relaxants used in medicine compete with acetylcholine for receptors, but do not cause the opening of ion channels.

These are so-called competitive anti-depolarizing muscle relaxants, which have a bulky molecule, and most of them contain 2 quaternary nitrogen atoms (two cationic centers).

Muscle relaxants do not penetrate the blood-brain barrier and the placenta.

Antidepolarizing muscle relaxants The competitive type of action blocks the NChR of the postsynaptic membrane of skeletal muscles and, thus, makes it impossible for the transmitter acetylcholine to connect with them. Due to this, there is no excitation of the NCR and subsequent depolarization of the muscle cell membrane, which is equivalent to the absence of cell excitation. With an increase in the concentration of acetylcholine, it is able to displace the blocker from the connection with the receptor and, thus, be its antagonist. To increase the content of acetylcholine (when it is necessary to restore neuromuscular conduction), anticholinesterase agents are administered ( prozerin). In this case, anticholinesterase drugs are used together with M-cholinergic blockers to prevent the M-cholinomimetic effects of acetylcholine (i.e., to narrow the spectrum of action of anticholinesterase drugs).

The choice of muscle relaxant often depends on its side effects, which include histamine liberation, M-anticholinergic, ganglion-blocking and sympathomimetic effects.

Tubocurarine has a relatively long-lasting muscle relaxant effect (30-60 min). Tubocurarine blocks ganglia, causing hypotension, and also stimulates the release of histamine, which can also help lower blood pressure.

Gallamine can cause unwanted tachycardia due to blockade of M2 cholinergic receptors (predominant in the myocardium).

Pancuronium – steroid drug, which has a fairly long-lasting muscle relaxant effect. May cause dose-dependent tachycardia.

Rocuronium– a new non-depolarizing muscle relaxant with a muscle relaxant effect lasting about 30 minutes. Its action is characterized by the rapid onset of muscle relaxation (after 1-2 minutes), which is similar to the effect of ditilin. The drug does not have cardiovascular effects.

Depolarizing muscle relaxants(ditylin (suxamethonium) is the only medicine of this type using

Dopamine receptor agonists play important role at initial treatment young people with Parkinson's disease. When treating elderly people and in late stages of Parkinson's disease, these drugs are advisable to use together with levodopa. Combination therapy allows you to reduce the dose of levodopa by 10-30%.

Ergoline drugs: bromocriptine (Parlodel) and pergolide (Permax)– derivatives of ergot alkaloids, are D2 receptor agonists.

Bromocriptine is a selective D2 receptor agonist; pergolide is a non-selective agonist of D1 and D2 receptors.

The drugs have distinct antiparkinsonian activity; inhibit the production of prolactin and growth hormone. They are prescribed orally, their bioavailability is low: most of them are inactivated during the first passage of the liver barrier.

Side effects:

· Gastrointestinal tract: anorexia, nausea, vomiting (these can be reduced by taking the drug with food)

· The cardiovascular system: often - orthostatic hypotension(at the beginning of therapy); vasospasm of the fingers (reversible by reducing the dose of the drug); arrhythmias are possible (the drug must be stopped)

Dyskinesia: abnormal movements similar to those seen with levadopa

· Mental disorders: disturbance of consciousness, hallucinations, delusions

· Other side effects: insomnia, pulmonary infiltrates, erythromelalgia (erythromelalgia: redness, pain and swelling of the extremities, which disappear after discontinuation of the drug).

Non-ergoline drugs: pramipexole (mirapex), ropinirole – agonists of D2 and D3 receptors. These are strong antiparkinsonian drugs. Due to their structural differences from ergot alkaloids, they do not have such side effects as erythromelalgia, vasospasm, and the formation of pulmonary infiltrates. The drugs are more effective than bromocriptine and are prescribed to patients with the disease as monotherapy medium degree severity, and in more severe cases of the disease - in combination with levodopa.

Side effects: orthostatic hypotension, increased fatigue, insomnia or drowsiness, peripheral edema, nausea, dyskinesia, impaired consciousness.

3. MAO B inhibitors. There are two types of monamine oxidase. Type A metabolizes norepinephrine and serotonin, type B metabolizes dopamine.

Selegiline (deprenyl) – selective inhibitor of monoamine oxidase B, inhibits dopamine inactivation. Consequently, it enhances and prolongs the antiparkinsonian effect of levodopa. Therefore, selegiline is used as an adjunct to therapy in patients with low effectiveness of levodopa. When used as monotherapy, the drug has minimal antiparkinsonian effect.

Selegiline has a neuroprotective effect: by inhibiting the oxidative metabolism of dopamine, it reduces the formation of free oxygen radicals, which cause the death of dopaminergic neurons.

Side effects: hallucinations, insomnia or drowsiness, speech and gait disturbances, diplopia, hypotension, arrhythmias.

COMT (catechol-ortho-methyltransferase) inhibitors

Suppression of DOPA decarboxylase leads to compensatory activation of other pathways of levodopa metabolism, especially to increased levels

3-methyldopa in plasma due to stimulation of catechol-ortho-methyltransferase. This in turn reduces the effect of levodopa. Selective COMT inhibitors tolcapone and entacapone prolong the effect of levodopa by inhibiting its metabolism in the periphery: the duration of the effect of levodopa increases, which makes it possible to reduce it daily dose. It is preferable to prescribe entacapone due to its lack of hepatotoxicity.

The pharmacological effects of tolcapone and entacapone are similar: they are both rapidly absorbed, bind to plasma proteins, and are metabolized. Tolcapone has both central and peripheral effects, while entacapone has only peripheral effects. The half-life of both drugs is approximately two hours, but tolcapone is slightly stronger and longer lasting.

Side effects of COMT inhibitors:

Increased levodopa toxicity (dyskinesia, nausea, confusion)

· Other side effects: diarrhea, abdominal pain, orthostatic hypotension, sleep disturbance, change in urine color; increased liver enzyme activity (tolcapone)

II. Substances that inhibit glutamatergic effects

Midantan (amantadine) blocks glutamate NMDA receptors and reduces the stimulating effect of glutamate neurons on the neostriatum, which prevails against the background of dopamine deficiency.

Pharmacokinetics. The maximum concentration of the drug in plasma is 1-4 hours after oral administration. The half-life is 2-4 hours, most of the drug is excreted unchanged by the kidneys.

Midantan reduces the manifestations of Parkinson's disease: rigidity, tremor, hypokinesia; It also has a neuroprotective effect on neurons of the substantia nigra. The drug is less effective than levodopa, its effects are shorter in duration and often wear off within just a few weeks of treatment.

Side effects:

CNS: depression, mental and motor agitation, irritability, insomnia, hallucinations, impaired consciousness

Other side effects: peripheral edema, congestive heart failure, orthostatic hypotension, anorexia

Midantan analogues: gludantan, memantine.

III. Drugs that inhibit cholinergic effects

Cyclodol, norakin (triperiden), akineton (biperiden), tropacin central M-anticholinergic blockers. They suppress stimulating cholinergic effects in the basal ganglia due to inhibition of central cholinergic receptors. The drugs reduce parkinsonian tremor and rigidity, but have almost no effect on bradykinesia. Widest clinical application has cyclodol.

Side effects:

CNS: drowsiness, slowness of thinking, restlessness, irritability, delirium, hallucinations

· Atropine-like effects: dry mouth, mydriasis, increased intraocular pressure, tachycardia, urinary retention, constipation

Table of drugs indicating routes of administration and release form

Write out prescriptions:

1. Antiparkinsonian drug – dopamine precursor

2. Combined antiparkinsonian drug

3. Central anticholinergic agent for parkinsonism

4. A remedy for parkinsonism – dopaminomimetic

5. Antiparkinsonian drug with antiviral properties

activity

6. A drug that activates the dopaminergic effect - an inhibitor

7. Antiparkinsonian drug, glutamatergic inhibitor

Questions for self-control:

1. Groups of substances are used for Parkinson’s disease

a) central anticholinergic blockers

b) peripheral M-anticholinergics

c) dopamine receptor blockers

d) dopamine receptor stimulants

e) MAO inhibitors

e) dopamine precursors

g) COMT inhibitors

2. Drugs are used for Parkinson's disease

a) cyclodol d) levodopa

b) diphenin e) sodium valproate

c) amantadine g) carbamazepine

d) entacapone

3. Combined antiparkinsonian drugs

a) gluferal c) fali-lepsin

b) sinemet d) madopar

4. The composition of combined antiparkinsonian drugs includes

peripheral DOPA decarboxylase inhibitors

a) benserazide d) selegiline

b) carbidopa d) contrical

c) dipyridamole e) carbidine

5. Side effects of cyclodol

a) increased intraocular pressure

b) tachycardia

c) nausea, vomiting

d) intestinal atony

e) stimulation of the central nervous system

e) respiratory depression

6. The mechanism of action of midantan is due to

a) inhibition of NMDA receptors

b) blockade of phosphodiesterase

c) blockade of DOPA decarboxylase

d) activation of sodium channels

e) inhibition of glutamatergic influences

7. Levodopa

a) used to prevent epilepsy

b) increases the content of dopamine in the central nervous system

c) relieves muscle rigidity and hypokinesia

d) blocks the conversion of DOPA to dopamine

d) turns into dopamine in neurons

8. Dopamine receptor agonists

a) bromocriptine d) pergolide

b) selegiline d) ropinirole

c) entacapone e) madopar

9. In Parkinson's disease in the nuclei of the extrapyramidal system

expedient

a) reduce the amount of dopamine

b) increase the amount of dopamine

c) increase the amount of acetylcholine

d) reduce the effects of acetylcholine

e) stimulate dopamine receptors

e) block dopamine receptors

g) reduce glutamatergic influences

10. Nakom is different from levodopa

c) the fact that it does not penetrate the BBB

d) more significant entry of levodopa into the central nervous system

11. Cyclodolus is characterized by

a) blockade of cholinergic receptors in the area of ​​the basal ganglia

b) the ability to block peripheral cholinergic receptors

c) dopamine reuptake disorder

d) stimulation of dopamine accumulation in the synaptic cleft

e) increased intraocular pressure

e) reduction of tremor and rigidity of skeletal muscles

12. Midantan

a) used for status epilepticus

b) is a direct antagonist of cyclodol

c) blocks glutamate receptors in the basal ganglia

d) has antiviral effect

d) is part of the drug "nakom"

13. The precursor to dopamine is

a) levodopa c) bromocriptine

b) midantan d) norepinephrine

14. Increase the content of dopamine in the synaptic cleft

a) levodopa c) atropine

b) madopar d) cyclodol

c) selegiline

15. Reduce the side effects of levodopa

a) carbidopa c) benserazide

b) DOPA decarboxylase d) dopamine

16. Carbidopa, benserazide

a) inhibitors of peripheral DOPA decarboxylase

b) reduce the formation of dopamine in peripheral tissues

c) are part of combined antiparkinsonian drugs

d) central DOPA decarboxylase inhibitors

e) increase the amount of levodopa entering the central nervous system

e) pass through the BBB

17. Selegiline

a) selectively inhibits MAO-B

b) suppresses the process of dopamine inactivation

c) effective for parkinsonism

d) inhibits MAO adrenergic sipases

e) suppresses the process of inactivation of norepinephrine

e) inhibits DOPA decarboxylase

18. Bromocriptine

a) dopamine D2 receptor agonist

b) effective for parkinsonism

c) effective for epilepsy

d) has sedative effect

d) inhibits the production of prolactin and growth hormone

e) causes galactorrhea

19. Groups of antiparkinsonian drugs that stimulate

dopaminergic processes in the brain

a) dopamine precursor

b) cholinergic receptor blockers

c) MAO-B inhibitors

d) dopamine receptor agonists

e) COMT inhibitors

20. Inhibits glutamatergic processes in the brain

a) cyclodol d) midantan

b) selegiline d) levodopa

c) bromocriptine e) glutantan

Answers to the recipe task:

1. Rp.: Levodopaе 0.25

D.t.d. N. 10 in caps.

S. 1 capsule 2 times a day

2. Rp.: Сaps. "Madopar-250" N. 100

D.S. 1 capsule 3 times a day

3. Rp.: Tab. Cyclodoli 0.001

S. 1 tablet 1 time per day

4. Rp.: Bromocriptini 0.01

D.t.d. N. 10 in caps.

S. 1 capsule 3 times a day

5. Rp.: Midantani 0.1

D.t.d. N. 10 in tab.

6. Rp.: Selegilini 0.01

D.t.d. N. 10 in tab.

S. 1 tablet 1 time per day

6. Rp.: Midantani 0.1

D.t.d. N. 10 in tab.

S. 1 tablet 2 times a day

Answers to self-control questions:

1. a, d, d, f, g

2. a, c, d, d

8. a, c, d, d

9. b, d, d, g

11. a, b, d, f

16. a, b, c, d

19. a, c, d, e

Bibliography:

1. Alyautdin R.N. Pharmacology.. M., 2004.

2. Bertram G. Katzung. Basic and clinical pharmacology. 2 edition, 1

volume. M., 2007.

3. Dzyak L. A., Zenkov L. R. Epilepsy. M., 2001.

4. Karlov V. A. Convulsive status epilepticus. M., 2003.

5. Medicines in Russia. Directory "Vidal". M., 2010.

6. Mashkovsky M. D. Medicines. 16th edition. M., 2010.

7. Guide to laboratory classes in pharmacology, edited by

D. A. Kharkevich. M., 2005.

8. Kharkevich D. A.. Pharmacology. 10th edition. M., 2009.

Almost any disease of the gastrointestinal tract is accompanied by a violation of the motor-evacuation function of its various parts. Simply put, illnesses slow down the movement of food coma through the organs and cause whole line unpleasant symptoms- from heartburn and vomiting to constipation and bloating. To stimulate the functioning of the stomach and intestines, it is customary to prescribe drugs from the list of prokinetic drugs that improve the tone of their smooth muscles.

How everything should work

Nature has created a complex mechanism for digesting food in the human body. Thanks to it, what we eat does not remain a lump in the throat, but gradually moves through the gastrointestinal tract, where it is processed by gastric juice and enzymes. This happens due to the fact that the walls of the stomach and intestines are covered with smooth muscles, which begin to “work” the moment food or drink passes from the pharynx into the esophagus.

Responsibility for the reflex work of muscles lies with dopamine (D2) and serotonin (5-HT 3, 5-HT 4) receptors. The first force them to relax so that the walls of the organ can stretch and accept a certain amount of food. The second ones cause contraction so that what is eaten moves further. In turn, they are given a signal by neurotransmitters - biologically active substances that are synthesized in human blood.

For one reason or another (most often due to chronic or infectious diseases of the gastrointestinal tract), a failure occurs in this well-functioning system. In this case, prokinetic drugs are prescribed as symptomatic or auxiliary therapy.

Classification of prokinetics by type of action

It is not difficult to guess that the mechanism of action of most prokinetics is based on blocking or stimulating certain receptors. Conventionally, they can be divided into three groups:

• agonists of serotonin receptors of the 5-HT 4 subtype;
• dopamine receptor blockers (divided into non-selective and selective first and second generation);
• antagonists of serotonin receptors of the 5-HT 3 subtype.

Such a classification of prokinetics allows us to examine in detail the differences between drugs grouped into different groups.

5-HT 4 receptor agonists

The easiest way to improve the peristalsis of the stomach and intestines is to activate serotonin receptors. Thanks to their action, food quickly passes through the digestive tract - accordingly, issues with heartburn, constipation, bloating and irritable bowel syndrome are eliminated. This group of prokinetics includes:

• cisapride (Peristil, Coordinax);
• tegaserod (Fractal, Zelmak).

Despite the fact that these prokinetics for stimulating bowel function have proven their effectiveness in practice, the advisability of their use is highly questionable. The fact is that the active substances in these drugs affect serotonin receptors not only in the gastrointestinal tract, but also in other organs, so their use often leads to disturbances in the functioning of the cardiovascular system.

Important: the sale of Propulsid (a product based on cisapride) was banned in the United States back in 2000, and the registration of Coordinax in Russia expired in 2001.

Dopamine receptor blockers

The essence of the action of these drugs is to prevent D 2 receptors from sending a signal to the muscles to relax. As a rule, drugs from this group not only improve gastrointestinal motility, but also have an antiemetic effect. They, in turn, are divided into the following subgroups:

• non-selective - they have a non-selective effect, and therefore affect not only the functioning of the gastrointestinal tract, but also the nervous system (cause drowsiness, lethargy, depressive states), the most famous representative is metoclopramide hydrochloride (Cerucal, Metoclopramide, Reglan);
• selective first generation - drugs based on the active substance domperidone act selectively and until recently were considered the best prokinetics for neutralizing heartburn and nausea (Gastropom, Motinorm, Motorix);
• selective II generation - despite their relatively recent presence on the market, prokinetics based on itopride hydrochloride have already proven themselves to be effective and non-addictive agents (Itomed, Primer, Ganaton).

5-HT 3 receptor antagonists

Drugs in this group of selective prokinetics promote the release of one of the neurotransmitters - acetylcholine. It stimulates choline receptors, and they, in turn, increase the peristalsis of the gastrointestinal tract. The products belong to the newest generation, and due to the small number of side effects (constipation, headache) are very quickly gaining recognition among doctors and patients.

This type of prokinetics includes drugs with the following active ingredients:

• ondansetron hydrochloride (Ondansetron, Ondanset, Osetron, Zofran);
• silansetron and tropisetron (drugs with similar names), alosetron (Lotronex).

Indications for the use of prokinetics

All prokinetic drugs can be purchased without a prescription. They are often taken without a doctor’s prescription in order to get rid of unpleasant symptoms:

• nausea and vomiting caused by dietary errors, infectious diseases of the gastrointestinal tract, chemotherapy and radiotherapy, diseases of the biliary tract;
• constipation and bloating;
• feeling of heaviness in the stomach after a heavy meal.

In addition, there are a number of diseases for the treatment of which modern prokinetics are used in complex therapy:

• peptic ulcer of the stomach or duodenum in acute or chronic form;
• diabetic gastroparesis;
• irritable bowel syndrome;

When should prokinetics not be used?

Even for the latest generation of prokinetics, there are contraindications for use due to their stimulating effect on almost all parts of the gastrointestinal tract:

• perforated peptic ulcer;
• stomach and intestinal bleeding;
• oncological diseases of these parts of the gastrointestinal tract;
• intestinal obstruction;
• chronic and infectious diseases kidney

Important: due to side effects such as drowsiness and inhibition of reactions, such drugs are not prescribed to people whose work requires increased concentration (for example, public transport drivers or electronic control panel operators). In addition, prokinetics should not be taken if there is an intolerance to one of their components.

Prokinetics in pediatrics and obstetrics

IN childhood Treatment with prokinetics is permissible only under the supervision of a specialist. If there is such a need, children from one year of age are prescribed medications with active substance domperidone. For them, such drugs are available in the form of suspensions, the dose of which is calculated depending on the child’s weight.

For vomiting caused by acute toxicosis in the first trimester, expectant mothers are allowed to take prokinetics only in extreme cases - if the malaise persists indomitable character and may pose a health risk. In further periods of pregnancy and during breastfeeding, such drugs should be avoided.

Why are prokinetics not always good?

Taking prokinetics, especially the first generations, can cause the following side effects in patients:

• headache;
• spasms of smooth muscles of the stomach and intestines;
• hyperexcitability or, on the contrary, inhibition of the nervous system;
• decreased effectiveness of drugs that are taken in parallel with prokinetics (due to rapid passage through the gastrointestinal tract);
• addiction (most often in older people).

Health from nature

The reluctance to encounter such effects of drugs forces us to seek help from nature. It turns out that natural prokinetics also exist. Our ancestors have long brewed or infused various parts of plants and improved the functioning of the intestines and stomachs without harm to health. They have a prokinetic effect:

• fennel and other plants of the umbrella family (cumin, coriander, dill);
• black elderberry;
• oregano;
• alder buckthorn;
• pharmaceutical camomile;
• big plantain.

You don’t have to go to the pharmacy or into nature to find natural prokinetics. Freshly prepared juices from pumpkin and cabbage, carrots and beets, grapes and melon can stimulate the functioning of the intestines and stomach just as well as any drug. This does not mean that you should replace medications prescribed by your doctor with juices, decoctions and tinctures, especially with complex therapy chronic diseases. Consultation with a specialist is necessary in any case.

(M-CHOLINOBLOCKERS, ATROPINE-LIKE DRUGS)

M-CHOLINOBLOCKERS OR M-CHOLINOLYTICS, DRUGS OF THE ATROPINE GROUP - these are drugs that block M-cholinergic receptors. A typical and most well-studied representative of this group is ATROPINE - hence the group is called atropine-like drugs. M-cholinergic blockers block peripheral Mcholinergic receptors located on the membrane of effector cells at the endings of postganglionic cholinergic fibers, that is, they block PARASYMPATHIC, cholinergic innervation. By blocking the predominantly muscarinic effects of acetylcholine, the effect of atropine on the autonomic ganglia and neuromuscular synapses does not extend.

Most atropine-like drugs block M-cholinergic receptors in the central nervous system.

An M-anticholinergic blocker with high selectivity of action is ATROPINE (Atropini sulfas; tablets 0.0005; ampoules 0.1% - 1 ml; 1% eye ointment).

ATROPINE is an alkaloid found in plants of the nightshade family. Atropine and related alkaloids are found in a number of plants:

Belladonna (Atropa belladonna);

Henbane (Hyoscyamus niger);

Datura stramonium.

Atropine is currently obtained synthetically, that is, chemically. The name Atropa Belladonna is paradoxical, since the term "Atropos" means "three fates leading to an inglorious end of life", and "Belladonna" means "charming woman" (donna is a woman, Bella is a female name in Romance languages). This term is due to the fact that the extract from this plant, instilled into the eyes of the beauties of the Venetian court, gave them a “shine” - dilated the pupils.

The mechanism of action of atropine and other drugs in this group is that by blocking M-cholinergic receptors, competing with acetylcholine, they prevent the mediator from interacting with them.

The drugs do not affect the synthesis, release and hydrolysis of acetylcholine. Acetylcholine is released, but does not interact with receptors, since atropine has a greater affinity (affinity) for the receptor. Atropine, like all M-cholinergic blockers, reduces or eliminates the effects of irritation of cholinergic (parasympathetic) nerves and the effect of substances with M-cholinomimetic activity (acetylcholine and its analogues, AChE agents, M-cholinomimetics). In particular, atropine reduces the effects of irritation n. vagus The antagonism between acetylcholine and atropine is competitive, therefore, when the concentration of acetylcholine increases, the effect of atropine at the point of application of muscarine is eliminated.

MAIN PHARMACOLOGICAL EFFECTS OF ATROPINE

1. Atropine has especially pronounced antispasmodic properties. By blocking M-cholinergic receptors, atropine eliminates the stimulating effect of parasympathetic nerves on smooth muscle organs. The tone of the muscles of the gastrointestinal tract, bile ducts and gallbladder, bronchi, ureters, and bladder decreases.

2. Atropine also affects the tone of the eye muscles. Let's look at the effects of atropine on the eye:

a) when atropine is administered, especially when applied topically, due to a block of M-cholinergic receptors in the circular muscle of the iris, pupil dilation is noted - mydriasis. Mydriasis also intensifies as a result of the preservation of the sympathetic innervation of m. dilatator pupillae. Therefore, atropine acts on the eye for a long time in this regard - up to 7 days;

b) under the influence of atropine, the ciliary muscle loses its tone, it becomes flattened, which is accompanied by tension in the ligament of Zinn, which supports the lens. As a result, the lens also flattens, and the focal length of such a lens lengthens. The lens sets vision to the far point of vision, so nearby objects are not clearly perceived by the patient. Since the sphincter is in a state of paralysis, it is not able to constrict the pupil when viewing nearby objects, and photophobia (photophobia) occurs in bright light. This condition is called ACCOMMODATION PARALYSIS or CYCLOPLEGIA. Thus, atropine is both a mydriatic and a cycloplegic. Local application A 1% atropine solution causes a maximum mydriatic effect within 30-40 minutes, and complete restoration of function occurs on average after 3-4 days (sometimes up to 7-10 days). Paralysis of accommodation occurs within 1-3 hours and lasts up to 8-12 days (approximately 7 days);

c) relaxation of the ciliary muscle and displacement of the lens into the anterior chamber of the eye is accompanied by a violation of the outflow of intraocular fluid from the anterior chamber. In this regard, atropine does not change intraocular pressure in healthy individuals, or in persons with a shallow anterior chamber and in patients with narrow-angle glaucoma, it may even increase, that is, lead to an exacerbation of an attack of glaucoma.

INDICATIONS FOR THE USE OF ATROPINE IN OPHTHALMOLOGY

1) In ophthalmology, atropine is used as a mydriatic to cause cycloplegia (paralysis of accommodation). Mydriasis is necessary when examining the fundus of the eye and in the treatment of patients with iritis, iridocyclitis and keratitis. IN the latter case atropine is used as an immobilization agent that promotes functional rest of the eye.

2) To determine the true refractive power of the lens when selecting glasses.

3) Atropine is the drug of choice if it is necessary to achieve maximum cycloplegia (paralysis of accommodation), for example, when correcting accommodative strabismus.

3. INFLUENCE OF ATROPINE ON ORGANS WITH SMOOTH MUSCLE. Atropine reduces the tone and motor activity (peristalsis) of all parts of the gastrointestinal tract. Atropine also reduces peristalsis of the ureters and the bottom of the bladder. In addition, atropine relaxes the smooth muscles of the bronchi and bronchioles. In relation to the biliary tract, the antispasmodic effect of atropine is weak. It should be emphasized that the antispasmodic effect of atropine is especially pronounced against the background of a previous spasm. Thus, atropine has an antispasmodic effect, that is, atropine acts in this case as an antispasmodic. And only in this sense can atropine act as a “painkiller”.

4. INFLUENCE OF ATROPINE ON THE ENDOCRECTION GLANDS. Atropine sharply weakens the secretion of all exocrine glands, with the exception of mammary glands. In this case, atropine blocks the secretion of liquid watery saliva caused by stimulation of the parasympathetic part of the autonomic nervous system, causing dry mouth. Tear production decreases. Atropine reduces volume and overall acidity gastric juice. In this case, suppression and weakening of the secretion of these glands can be up to their complete shutdown. Atropine reduces the secretory function of glands in the cavities of the nose, mouth, pharynx and bronchi. The secretion of the bronchial glands becomes viscous. Atropine, even in small doses, inhibits the secretion of SWEAT GLANDS.

5. INFLUENCE OF ATROPINE ON THE CARDIOVASCULAR SYSTEM. Atropine, taking the heart out of control n. vagus, causes TACHYCARDIA, that is, it increases the heart rate. In addition, atropine helps facilitate the conduction of impulses in the conduction system of the heart, in particular in the AV node and along the atrioventricular bundle as a whole. These effects are less pronounced in elderly people, since in therapeutic doses atropine does not have a significant effect on peripheral blood vessels, they have reduced tone n. vagus Atropine does not have a significant effect on blood vessels in therapeutic doses.

6. INFLUENCE OF ATROPINE ON THE CNS. In therapeutic doses, atropine has no effect on the central nervous system. In toxic doses, atropine sharply excites the neurons of the cerebral cortex, causing motor and speech excitation, reaching mania, delirium and hallucinations. The so-called “atropine psychosis” occurs, leading further to a decrease in function and the development of coma. It also has a stimulating effect on the respiratory center, but with increasing doses, respiratory depression may occur.

INDICATIONS FOR USE OF ATROPINE (except ophthalmological)

1) As an ambulance for:

a) intestinal

b) renal

c) hepatic colic.

2) For bronchospasms (see adrenergic agonists).

3) In complex therapy of patients with peptic ulcer of the stomach and duodenum (reduces the tone and secretion of the glands). It is used only in a complex of therapeutic measures, since it reduces secretion only in large doses.

4) As a means of presedation in anesthesiological practice, atropine is widely used before surgery. As a means drug preparation In patients undergoing surgery, atropine is used because it has the ability to suppress the secretion of the salivary, nasopharyngeal and tracheobronchial glands.

As is known, many anesthetics (ether in particular) are strong irritants of the mucous membranes. In addition, by blocking M-cholinergic receptors of the heart (the so-called vagolytic effect), atropine prevents negative reflexes on the heart, including the possibility of its reflex stop.

By using atropine and reducing the secretion of these glands, they prevent the development of inflammatory diseases. postoperative complications in the lungs. This explains the importance of the fact that resuscitation doctors attach when they talk about the full opportunity to “breathe” the patient.

5) Atropine is used in cardiology. Its M-anticholinergic effect on the heart is beneficial in some forms of cardiac arrhythmias (for example, atrioventricular block of vagal origin, that is, with bradycardia and heart block).

6) Wide Application found atropine as an emergency remedy for poisoning:

a) AChE means (FOS)

b) M-cholinomimetics (muscarine).

Along with atropine, other atropine-like drugs are well known. Natural atropine-like alkaloids include SCOPOLAMINE (hyoscine) Scopolominum hydrobromidum. Available in ampoules of 1 ml - 0.05%, as well as in the form of eye drops (0.25%). Contained in the mandrake plant (Scopolia carniolica) and in the same plants that contain atropine (belladonna, henbane, datura). Structurally close to atropine. It has pronounced M-anticholinergic properties. There is one significant difference from atropine: in therapeutic doses, scopolamine causes mild sedation, central nervous system depression, sweating and sleep. It has a depressing effect on the extrapyramidal system and the transmission of excitation from the pyramidal tracts to the motor neurons of the brain. Introducing the drug into the conjunctival cavity causes less prolonged mydriasis.

Therefore, anesthesiologists use scopolomine (0.3-0.6 mg s.c.) as a premedication, but usually in combination with morphine (but not in the elderly, as it can cause confusion). It is sometimes used in psychiatric practice as a sedative, and in neurology for the correction of parkinsonism. Scopolamine has a shorter duration of action than atropine. They are also used as an antiemetic and sedative for sea and airborne illnesses (Aeron tablets are a combination of scopolamine and hyoscyamine).

PLATIFYLLINE also belongs to the group of alkaloids obtained from plant raw materials (rhombolic ragwort). (Platyphyllini hydrotartras: tablets of 0.005, as well as ampoules of 1 ml - 0.2%; eye drops- 1-2% solution). It acts in much the same way, causing similar pharmacological effects, but weaker than atropine. It has a moderate ganglion-blocking effect, as well as a direct myotropic antispasmodic effect (papaverine-like), as well as on the vasomotor centers. Has a calming effect on the central nervous system. Platiphylline is used as an antispasmodic for spasms of the gastrointestinal tract, bile ducts, gallbladder, ureters, with increased tone of the brain and coronary vessels, as well as for the relief of bronchial asthma. In ophthalmic practice, the drug is used to dilate the pupil (it has a shorter effect than atropine and does not affect accommodation). It is administered under the skin, but it should be remembered that solutions of 0.2% concentration (pH = 3.6) are painful.

For ophthalmic practice, HOMATROPINE (Homatropinum: 5 ml bottles - 0.25%) is proposed. It causes pupil dilation and paralysis of accommodation, that is, it acts as a mydriatic and cycloplegic. The ophthalmic effects caused by homatropine last only 15-24 hours, which is much more convenient for the patient compared to the situation when atropine is used. The risk of raising IOP is less, since atropine is weaker, but at the same time, the drug is contraindicated for glaucoma. Otherwise, it is not fundamentally different from atropine; it is used only in ophthalmic practice.

The synthetic drug METACIN is a very active M-anticholinergic blocker (Methacinum: in tablets - 0.002; in ampoules 0.1% - 1 ml. A quaternary ammonium compound that poorly penetrates the BBB. This means that all its effects are due to peripheral M - anticholinergic effect. It differs from atropine in its more pronounced bronchodilator effect, the absence of an effect on the central nervous system. Stronger than atropine, it suppresses the secretion of the salivary and bronchial glands. Used for bronchial asthma, peptic ulcer disease, for the relief of renal and hepatic colic, for premedication in anesthesiology (in /in - in 5-10 minutes, intramuscularly - in 30 minutes) - more convenient than atropine. The analgesic effect is superior to atropine, causes less tachycardia.

Among medicines containing atropine, belladonna (belladonna) preparations are also used, for example, belladonna extracts (thick and dry), belladonna tinctures, and combined tablets. These are weak drugs and are not used in ambulances. Used at home at the pre-hospital stage.

Finally, a few words about the first representative of selective muscarinic receptor antagonists. It turned out that in different organs of the body there are different subclasses of muscarinic receptors (M-one and M-two). Recently, the drug gastrocepin (pirenzepine) was synthesized, which is a specific inhibitor of M-one cholinergic receptors of the stomach. Clinically, this is manifested by intense inhibition of gastric juice secretion. Due to the pronounced inhibition of gastric juice secretion, gastrocepin causes persistent and rapid pain relief. Used for stomach and duodenal ulcers, gastritis, daudenitis. It has significantly fewer side effects and has virtually no effect on the heart and does not penetrate into the central nervous system.

SIDE EFFECTS OF ATROPINE AND ITS DRUGS. In most cases, side effects are a consequence of the breadth pharmacological action of the studied drugs and are manifested by dry mouth, difficulty swallowing, intestinal atony (constipation), blurred visual perception, tachycardia. Topical use of atropine can cause allergic reactions (dermatitis, conjunctivitis, swelling of the eyelids). Atropine is contraindicated for glaucoma.

ACUTE POISONING WITH ATROPINE, ATROPINE-LIKE DRUGS AND PLANTS CONTAINING ATROPINE. Atropine is far from a harmless drug. Suffice it to say that even 5-10 drops can be toxic. The lethal dose for adults when taken orally begins with 100 mg, for children - with 2 mg; When administered parenterally, the drug is even more toxic. The clinical picture of poisoning with atropine and atropine-like drugs is very characteristic. There are symptoms associated with the suppression of cholinergic influences and the effect of the poison on the central nervous system. At the same time, depending on the dose of the ingested medication, MILD and SEVERE courses are distinguished.

At mild poisoning The following clinical signs develop:

1) dilated pupils (mydriasis), photophobia;

2) dry skin and mucous membranes. However, due to decreased sweating skin hot, red, there is an increase in body temperature, a sharp flushing of the face (the face is “bursting with heat”);

3) dry mucous membranes;

4) severe tachycardia;

5) intestinal atony. In case of severe poisoning against the background of all

indicated symptoms on

the foreground is PSYCHOMOTOR EXCITATION, that is, both mental and motor excitement. Hence the well-known expression: “I’ve eaten too much henbane.” Motor coordination is impaired, speech is blurred, consciousness is confused, and hallucinations are noted. Phenomena of atropine psychosis are developing, requiring the intervention of a psychiatrist. Subsequently, depression of the vasomotor center may occur with a sharp expansion of the capillaries. Collapse, coma and respiratory paralysis develop.

HELP MEASURES FOR ATROPINE POISONING If the poison is taken

inside, then an attempt should be made to pour it in as quickly as possible (gastric lavage, laxatives, etc.); astringents - tannin, adsorbents - Activated carbon, forced diuresis, hemosorption. It is important to apply specific treatment here.

1) Before washing, a small dose (0.3-0.4 ml) of sibazon (Relanium) should be administered to combat psychosis, psychomotor agitation. The dose of sibazon should not be large, as the patient may develop paralysis of vital centers.

In this situation, aminazine cannot be administered, since it has its own muscarinic-like effect.

2) It is necessary to displace atropine from its connection with cholinergic receptors; various cholinomimetics are used for these purposes. It is best to use physostigmine (iv, slowly, 1-4 mg), which is what they do abroad. We use AChE agents, most often prozerin (2-5 mg, s.c.). Medicines are administered at intervals of 1-2 hours until signs of elimination of the blockade of muscarinic receptors appear. The use of physostigmine is preferable because it penetrates well through the BBB into the central nervous system, reducing the central mechanisms of atropine psychosis. To alleviate photophobia, the patient is placed in a darkened room and rubbed cool water. Careful care is required. Often required artificial respiration.

N-CHOLINERGIC DRUGS

Let me remind you that H-cholinergic receptors are localized in the autonomic ganglia and end plates of skeletal muscles. In addition, H-cholinergic receptors are located in the carotid glomeruli (they are necessary to respond to changes in blood chemistry), as well as the adrenal medulla and the brain. The sensitivity of H-cholinergic receptors of different localization to chemical compounds is not the same, which makes it possible to obtain substances with a predominant effect on the autonomic ganglia, cholinergic receptors of neuromuscular synapses, and the central nervous system.

Drugs that stimulate H-cholinergic receptors are called H-cholinomimetics (nicotinomimetics), and those that block them are called H-cholinergic blockers (nicotine blockers).

It is important to emphasize the following feature: all H-cholinomimetics excite H-cholinergic receptors only in the first phase of their action, and in the second phase the excitation is replaced by an inhibitory effect. In other words, N-cholinomimetics, in particular the reference substance nicotine, have a two-phase effect on H-cholinergic receptors: in the first phase, nicotine acts as an N-cholinomimetic, in the second - as an N-cholinergic blocker.

N-CHOLINOMIMEtics OR DRUGS THAT STIMULATE NICOTINE-SENSITIVE CHOLINORESCEPTORS. This group includes alkaloids: nicotine, lobeline and cytisine (cytitone).

Since nicotine has no therapeutic value, we will focus on the last 2 N-cholinomimetics (lobeline and cytisine).

Let's analyze the drug Cytitonum (amp. 1 ml), representing a 0.15% solution of cytisine. Cytisine itself is an alkaloid from broom (Cytisus laburnum) and thermopsis (Termopsis lanceolata) plants. A special feature of the drug cititon is that it more or less selectively excites the H-cholinergic receptors of the carotid glomeruli and the adrenal medulla, without affecting the remaining N-cholinergic receptors. The respiratory center is reflexively excited, and blood pressure levels increase.

Cititon is used to stimulate the respiratory center when it is depressed. When cititon is administered, as a drug that reflexively excites the respiratory center, after 3-5 minutes there is an excitation of breathing and an increase in blood pressure by 10-20 mm Hg. Art., for 15-20 minutes.

The drug acts reflexively, jerkily, and for a short time. It is used to excite the respiratory center with preserved reflex excitability (to the point of coma) of the respiratory center. Currently used for one indication: for carbon monoxide (CO) poisoning. Now, essentially, this is the only indication in the clinic. In experimental pharmacology it is used to determine blood flow time.

There is a similar drug - LOBELIN (Lobelini hydrochloridum: amp. 1%, 1 ml). The action is exactly the same as qi

Tithonian, but somewhat weaker than the latter.

Both drugs are used to stimulate breathing. Administer intravenously (only, since the action is reflex). In addition, both alkaloids are used as the main components of drugs that facilitate quitting tobacco smoking (cytisine in Tabex tablets, lobeline in Lobesil tablets). Weak drugs. They helped a small number of people stop smoking.

N-CHOLINOBLOCKERS OR NICOTINE SENSE BLOCKING DRUGS

BODY CHOLINORESEPTORS

Drugs with an H-anticholinergic effect include 2 groups of drugs:

1) ganglion blocking agents or ganglion blockers;

2) neuromuscular junction blockers or muscle relaxants.

In addition, there are central anticholinergic blockers. GANGLIOB

LOCATORS, that is, means that block the transmission of excitation in the autonomic ganglia. Ganglioblockers block

Sympathetic N-cholinergic receptors

and parasympathetic ganglia, as well as the adrenal medulla and carotid glomerulus. There are currently a significant number of ganglion blockers.

According to the mechanism of action, ganglion blockers used in the clinic are classified as antidepolarizing substances. They block H-cholinergic receptors, preventing the depolarizing effect of acetylcholine.

The first ganglion blocker was Benzohexonium (tables of 0.1 and 0.25; amp. 1 ml - 2.5%). Then Pentaminum appeared (amp. 1 and 2 ml - 5%). Pyrylene, hygronium, pachycarpine, etc. To the main pharmaceuticals

The ecological effects observed during the sorptive action of ganglion blockers include the following:

1) a disturbance in the transmission of impulses in the parasympathetic ganglia is manifested by inhibition of the secretion of the salivary glands, gastric glands, and inhibition of motility of the digestive tract. In this regard, ganglion blockers are used for very severe forms of peptic ulcer;

2) as a result of inhibition of the sympathetic ganglia, blood vessels (arterial and venous) dilate, arterial and venous pressure decreases. Vasodilation leads to improved blood circulation in the relevant areas, regions, and tissues. From here follows a group of indications.

Indications for the use of ganglion blockers:

1) with spasms of peripheral vessels (for example, with obliterating endarthritis); Previously - in the 60s - they were considered very valuable means;

2) in the most severe forms hypertension(hypertic crisis) with left ventricular failure;

3) in intensive care - with acute edema lungs, brain;

4) for controlled hypotension (hypotension). This is necessary when performing operations on the heart, on large vessels, on the thyroid gland, and during mastectomy (breast surgery). For this purpose, short-acting ganglion blockers (arfonade, hygronium) are used, the effect of which lasts 10-15 minutes. In addition, these drugs are used for acute hypertensive encephalopathy, dissecting aortic aneurysm, and retinopathy. Typically, ganglion blockers are used orally, but in emergency cases they are administered intravenously or intramuscularly.

MAIN DISADVANTAGE AND MAIN SIDE EFFECTS OF GANGLION BLOCKERS. The main disadvantage of ganglion blockers is the lack of selectivity of action. Among the side effects it should be noted frequent development arthostatic collapse, that is, when, when taking a vertical position, the patient’s blood pressure sharply decreases (fainting, collapse).

To prevent the development of this condition, the patient is recommended to stay in bed for 2 hours after taking ganglion blockers.

In case of severe poisoning with ganglion blockers, a drop in blood pressure to 0 (zero) is observed, and in case of very severe poisoning, skeletal atony may even develop. This occurs when ganglion blockers lose their selectivity of action on the H-cholinergic receptors of the ganglia and then act on all H-receptors, including skeletal muscles.

Often, when taking ganglion blockers, constipation (obstipation) is observed, there may be mydriasis, urinary retention, and more. In addition, tolerance to ganglion blockers quickly develops.

ASSISTANCE MEASURES IN CASE OF POISONING WITH GANGLION BLOCKERS. Everything needs to be carried out as indicated earlier to combat the poison in the patient’s body. Give oxygen, put on artificial respiration, administer analeptics, AChE agents, proserin (ganglionic blocker antagonists). Raising blood pressure (adrenergic agonists) and from these positions the drug ephedrine looks a little better.

DRUGS BLOCKING N-CHOLINORECEPTORS OF SKELETAL MUSCLES

(CURARE-LIKE DRUGS OR PERIPHERAL MUSTERELXANTS

ACTIONS)

The main effect of this group of pharmacological agents is the relaxation of skeletal muscles as a result of the blocking effect of substances on neuromuscular transmission. Since such properties were first discovered in CURARE, the substances of this group were called curare-like agents.

CURARE is an extract from plants native to South America. Aborigines South America Curare poison has been used for a long time as an arrow poison. Since the 40s of the 20th century they began to use it in medicine. Curare contains a significant number of different alkaloids, one of the main ones being TUBOCURARINE. Now (mostly synthetics) a number of synthetic and semi-synthetic drugs have been obtained that block the transmission of excitation from motor nerves to skeletal muscles.

BY CHEMICAL STRUCTURE, all curare-like drugs belong either to quaternary (dioxonium, tubocurarine, pancuronium, ditilin) ​​ammonium compounds (they are less absorbed), or they are tertiary amines (they penetrate the BBB poorly; pachycarpine, pyrylene, melliktin, candelphin, etc.).

MECHANISM OF ACTION OF CURARE-LIKE DRUGS. Muscle relaxants inhibit neuromuscular transmission at the level of the postsynaptic membrane by interacting with cholinergic receptors in the end plates.

The neuromuscular block caused by different muscle relaxants does not have the same genesis. The classification of curare-like drugs is based on this. Based on the mechanism of action, muscle relaxants are divided into 3 groups of drugs:

1) anti-depolarizing (non-depolarizing) agents (prevent membrane depolarization): tubocurarine, anatruxonium, pancuronium, melliktin, diplacin;

2) depolarizing agents (ditilin) ​​- significantly contribute to depolarization;

3) mixed type agents - dioxin. Currently, there are many new synthetic products of mixed type.

ANTI-DEPOLARIZING DRUGS, as follows from the definition, block H-cholinergic receptors and interfere with the depolarizing effect of acetylcholine.

DEPOLARIZING DRUGS such as dithiline - excite H-cholinergic receptors and cause persistent depolarization of the postsynaptic membrane, thereby providing a persistent myoparalytic effect (if acetylcholine acts for 0.001-0.002 seconds, then dithiline - 5-7 minutes).

MIXED TYPE DRUGS (dioxonium) combine depolarizing and antidepolarizing properties. In the light of modern views, these effects are associated with ionic relaxation mechanisms. There is a blockade of ion channels and, accordingly, a blockade of ion currents. Muscle relaxants relax muscles in a specific sequence: most drugs first block the neuromuscular junctions of the face and neck, then the limbs and torso. The respiratory muscles are the most resistant to the action of muscle relaxants. Lastly, the diaphragm is paralyzed, which is accompanied by cessation of breathing. During the period when paralysis progresses, consciousness and sensitivity are not impaired. Recovery proceeds in reverse order. It has now been revised, and muscle relaxants are being created with a predominant effect on certain groups of skeletal muscles.

There are SHORT-acting muscle relaxants (5-10 minutes), these include ditilin; MEDIUM duration (20-50 minutes) - tubocurarine, pancuronium, anatruxonium and LONG acting(60 minutes or more) - anatruxonium, pylecuronium, etc. in large doses.

Based on the mechanism of action, antagonists of curare-like drugs are selected. For anti-depolarizing competitive agents, active antagonists are AChE agents (proserine, galantamine, pyridostigmine, edrophonium). In addition, agents have now been developed to promote the release of acetylcholine from the endings of motor nerves (pimadine).

In case of an overdose of depolarizing agents (ditilin), AChE agents are ineffective (on the contrary, even). Therefore, the assistance measures are different. First of all, they use the introduction of fresh citrated blood containing plasma cholinesterase, which hydrolyzes dithiline (which is a double acetylcholine molecule in structure). In addition, ventilation! Route of administration: i.v. But there are drugs for per os.

INDICATIONS FOR USE. The main purpose of muscle relaxants is to relax skeletal muscles during major operations and various surgical interventions. Relaxing skeletal muscles greatly facilitates:

1) performing many operations on the organs of the abdominal and thoracic cavities, as well as on the limbs. Use long-acting drugs;

2) muscle relaxants are used for tracheal intubation, bronchoscopy, correction of dislocations and reposition of bone fragments. In this case, short-acting drugs (ditilin) ​​are used;

3) in addition, the drugs are used in the treatment of patients with tetanus, status epilepticus, and electroconvulsive therapy (d-tubocurarine is used to diagnose myasthenia gravis);

4) tertiary amines (mellictin, codelfin - larkspur alkaloids), used in some diseases of the central nervous system to reduce increased skeletal muscle tone (per os).

SIDE EFFECTS. Side effects when using curare-like drugs are not of a threatening nature. However, one should always keep in mind the instability of blood pressure.

1) Blood pressure can decrease (tubocurarine, anatruxonium) and increase (ditilin).

2) Some drugs (anatruxonium, pancuronium) have a pronounced H-anticholinergic (vagolytic) effect on the heart, which leads to tachycardia.

Depolarizing (ditylin) muscle relaxants, in the process of depolarization of the postsynaptic membrane, cause the release of potassium ions from skeletal muscles and its content in the blood plasma increases. This is facilitated by muscle microtrauma. Hyperkalemia, in turn, causes cardiac arrhythmias. By promoting the release of histamine, tubocurarine increases bronchial muscle tone (bronchospasm), and ditilin increases intraocular pressure. Ditylin > intraventricular pressure. In addition, when using depolarizing muscle relaxants (ditilin), muscle pain is typical.

Finally, when using antidepolarizing agents, one should be aware of their accumulation upon repeated administration.