M -cholinergic receptors stimulated by the fly agaric poison muscarine and blocked by atropine. They are localized in the nervous system and internal organs that receive parasympathetic innervation (they cause cardiac depression, smooth muscle contraction, and increase the secretory function of the exocrine glands) (Table 15 in Lecture 9). M-cholinergic receptors are associated with G-proteins and have 7 segments that cross the cell membrane like a serpentine.
Molecular cloning has made it possible to identify five types of M-cholinergic receptors:
1. M 1 -cholinergic receptors CNS (limbic system, basal ganglia, reticular formation) and autonomic ganglia;
2. M 2 -cholinergic receptors heart (reduce heart rate, atrioventricular conduction and myocardial oxygen demand, weaken atrial contractions);
3. M 3 -cholinergic receptors:
· smooth muscles (cause constriction of the pupils, spasm of accommodation, bronchospasm, spasm of the biliary tract, ureters, contraction of the bladder, uterus, increase intestinal motility, relax sphincters);
· glands (cause lacrimation, sweating, copious secretion of liquid, protein-poor saliva, bronchorrhea, acid secretion gastric juice).
· Extrasynaptic M 3 -cholinergic receptors are located in the vascular endothelium and regulate the formation of the vasodilator factor - nitric oxide (NO).
· 4. M 4 - and M 5 -cholinergic receptors have less functional significance.
· M 1 -, M 3 - and M 5 - cholinergic receptors, activating through G q /11-protein phospholipase C of the cell membrane, increases the synthesis of secondary messengers - diacylglycerol and inositol triphosphate. Diacylglycerol activates protein kinase C, inositol triphosphate releases calcium ions from the endoplasmic reticulum,
· M 2 - and M 4 -cholinergic receptors with the participation G i - And G 0-proteins inhibit adenylate cyclase (inhibit cAMP synthesis), block calcium channels, and also increase the conductivity of potassium channels in the sinus node.
· Additional effects of M-cholinergic receptors are mobilization of arachidonic acid and activation of guanylate cyclase.
· H-cholinergic receptors stimulated by the tobacco alkaloid nicotine in small doses, blocked by nicotine in large doses.
· Biochemical identification and isolation of H-cholinergic receptors became possible thanks to the discovery of their selective high-molecular ligand α-bungarotoxin - the venom of the Taiwanese viper Bungarus multicintus and cobras Naja naja. H-cholinergic receptors are located in ion channels; within milliseconds they increase the permeability of the channels for Na +, K + and Ca 2+ (5 - 10 7 sodium ions pass through one channel of the skeletal muscle membrane in 1 s).
1. Cholinomimetic drugs: a) m-n-cholinomimetics direct action(acetylcholine, carbacholine); b) m-n-cholinomimetics of indirect action, or anticholinesterase (physostigmine, proserin, galantamine, phosphakol); b) m-choliomimetics (pilocarpine, aceclidine); c) n-cholinomimetics (lobeline, cititon).
2. Anticholinergic drugs: a) m-anticholinergics (atropine, platiphylline, scolamine, hyoscyamine, homatropine, metacin); b) n-anticholinergic-ganglionic blockers (benzohexonium, pentamine, pachycarpine, arfonade, hygronium, pyrylene); muscle relaxants (tubocurarine, ditilin, anatruxonium).
Cholinomimetic drugs. Direct acting m-n-cholinomimetics. ACh is quickly destroyed by cholinesterase, therefore it acts for a short time (5-15 minutes with subcutaneous administration), carbacholin is destroyed slowly and acts for up to 4 hours. These substances produce all the effects associated with the excitation of cholinergic nerves, i.e. muscarinic and nicotine-like.
Excitation of m-HR leads to an increase in smooth muscle tone, an increase in the secretion of the digestive, bronchial, lacrimal and salivary glands. This is manifested by the following effects. Constriction of the pupil (miosis) occurs as a result of contraction of the circular muscle of the iris; decline intraocular pressure, since when the iris muscle contracts, the helmet canal and fountain spaces expand, through which the outflow of fluid from the anterior chamber of the eye increases; spasm of accommodation as a result of contraction of the ciliary muscle and relaxation of the ligament of cinnamon, regulating the curvature of the lens, which becomes more convex and is installed at the near point of vision. Secretion lacrimal glands increases. On the part of the bronchi, there is an increase in smooth muscle tone and the development of bronchospasm, and an increase in the secretion of the bronchial glands. The tone and peristalsis of the gastrointestinal tract increases, the secretion of the digestive glands increases, the tone of the gallbladder and biliary tract increases, and the secretion of the pancreas increases. The tone of the bladder, ureters, and urethra increases, and the secretion of sweat glands increases. Stimulation of m-ChR of the cardiovascular system is accompanied by a decrease in heart rate, a slowdown in conduction, automaticity and contractility of the myocardium, dilation of blood vessels in skeletal muscles and pelvic organs, and a decrease in blood pressure. Excitation of n-ChR manifests itself by increased and deepening of breathing as a result of stimulation of the receptors of the carotid sinus (carotid glomeruli), from where the reflex is transmitted to the respiratory center. The release of adrenaline from the adrenal medulla into the blood increases, but its cardiotonic and vasoconstrictive effects are suppressed by depression of the heart and hypotension as a result of stimulation of m-ChR. The effects associated with increased transmission of impulses through the sympathetic ganglia (vasoconstriction, increased cardiac function) are also masked by the effects caused by the excitation of m-ChR. If you pre-administer atropine, which blocks m-ChR, then the effect of m-choliomimetics on n-ChR is clearly manifested. ACH and carbacholin increase the tone of skeletal muscles and can cause fibrillation. This effect is associated with increased transmission of impulses from the endings motor nerves on muscles as a result of n-AChR stimulation. In large doses, they block n-AChR, which is accompanied by inhibition of ganglionic and neuromuscular conduction and a decrease in the secretion of adrenaline from the adrenal glands. These substances do not penetrate the BBB, since they have ionized molecules, and therefore do not affect the central nervous system in normal doses. Carbacholine can be used to reduce intraocular pressure in glaucoma and bladder atony.
· Mn-cholinomimetics of indirect action (anticholinesteoase). These are substances that stimulate m- and n-ChRs due to the accumulation of ACh in synapses. MD is caused by inhibition of cholinesterase, which leads to a slowdown in the hydrolysis of ACh and an increase in its concentration in synapses. The accumulation of ACh under their influence reproduces all the effects of ACh (with the exception of stimulation of respiration). The above effects associated with stimulation of m- and n-AChRs are characteristic of all cholinesterase inhibitors. Their effect on the central nervous system depends on penetration through the BBB. Substances containing tertiary nitrogen(physostigmine, galantamine, phosphakol) penetrate well into the brain and enhance cholinergic effects, while substances with quaternary nitrogen (proserin) penetrate poorly and act predominantly on peripheral synapses.
By the nature of the effect on cholinesterase they are divided into substances reversible and irreversible action. The first include physostigmine, galantamine and proserine. They cause reversible inactivation of cholinesterase, as they form a weak bond with it. The second group consists organophosphorus compounds (FOS), which are used not only in the form of drugs (phosphacol), but also to kill insects (chlorophos, dichlorvos, karbofos, etc.), and also as nerve agents (sarin, etc.). they form a strong covalent bond with cholinesterase, which is very slowly hydrolyzed by water (about 20 days). Therefore, the inhibition of cholinesterase becomes irreversible.
Anticholinesterase drugs apply for the following diseases: 1) residual effects after poliomyelitis, skull injuries, cerebral hemorrhages (galantamine); 2) myasthenia gravis - a disease characterized by progressive muscle weakness (prozerin, galantamine); 3) glaucoma (phosphacol, physostigmine); 4) atony of the intestines, bladder (prozerin); 5) overdose of muscle relaxants (prozerin). These substances are contraindicated in bronchial asthma and heart diseases with conduction disorders. Poisoning most often occur when FOS, which have an irreversible effect, enters the body. Initially, miosis develops, impaired accommodation of the eye, salivation and difficulty breathing, increased blood pressure, and the urge to urinate. Muscle tone increases, bronchospasm intensifies, breathing becomes more difficult, bradycardia develops, blood pressure decreases, vomiting, diarrhea, fibrillary muscle twitching, and attacks of clonic convulsions occur. Death is usually associated with severe respiratory failure. First aid consists of the administration of atropine, cholinestease reactivators (diperoxime, etc.), barbiturates (to relieve seizures), hypertensive drugs (mesaton, ephedrine), artificial ventilation lungs (preferably oxygen). M-cholinomimetics. Muscarine is not used due to its high toxicity. It is used in scientific research. Used as a drug pilocarpine and aceclidine. The MD of these drugs is associated with direct stimulation of m-ChR, which is accompanied by pharmacological effects caused by their excitation. They are manifested by constriction of the pupil, a decrease in intraocular pressure, a spasm of accommodation, an increase in the tone of the smooth muscles of the bronchi, gastrointestinal tract, bile and urinary tract, increased secretion of bronchial, digestive glands, sweat glands, decreased automaticity, excitability, conductivity and contractility of the myocardium, dilation of blood vessels in skeletal muscles, genitals, decreased blood pressure. Of these effects, a decrease in intraocular pressure and an increase in intestinal tone are of practical importance. The remaining effects most often cause undesirable consequences: a spasm of accommodation disrupts the adaptation of vision, depression of the heart can cause circulatory disorders and even sudden stop hearts (syncope). Therefore, administering these drugs intravenously is not recommended. A decrease in blood pressure is also undesirable. bronchospasm, hyperkinesis.
The effect of m-cholinomimetics on the eye is great importance in the treatment of glaucoma, which often causes exacerbations (crises), which are common cause blindness and therefore require emergency treatment. Instillation of cholinomimetics into the eye causes a decrease in intraocular pressure. They are also used for intestinal atony. Used for glaucoma pilocarpine, with atony - aceclidine, which produces fewer side effects. M-cholinomimetics are contraindicated in bronchial asthma, conduction disorders in the heart, serious illnesses heart, with epilepsy, hyperkinesis, pregnancy (due to the risk of miscarriage). In case of poisoning m-cholinomimetics(most often with fly agaric) first aid consists of gastric lavage and administration of atropine, which is an antagonist of these substances due to the blockade of m-ChR.
· N-cholinominetics. Nicotine has no medicinal value. When smoked along with tobacco combustion products, it contributes to the development of many diseases. Nicotine has high toxicity. Along with smoke, other toxic products are inhaled when smoking: tar, phenol, carbon monoxide, hydrocyanic acid, radioactive polonium, etc. The attraction to Smoking is caused by the pharmacological effects of nicotine associated with the stimulation of n-ChRs of the central nervous system (cortex, medulla oblongata and spinal cord), which is accompanied by a subjective feeling of increased performance. The release of adrenaline from the adrenal glands, which increases blood circulation, is also important. Habit and the psychological impact of the environment play a big role in the development of desire. Smoking promotes development cardiovascular diseases(hypertension, angina pectoris, atherosclerosis, etc.), bronchopulmonary diseases (bronchitis, emphysema, lung cancer), gastrointestinal diseases (peptic ulcer, gastritis). Getting rid of this bad habit depends primarily on the smoker himself. This can be helped by some drugs (for example, Tabex) containing cytisine or lobeline.
· Lobelin And cititon selectively stimulate n-AChR. Of practical importance is the excitation of n-AChR of the carotid glomeruli, which is accompanied by reflex excitation respiratory center. Therefore, they are used as respiratory stimulants. The effect is short-term (2-3 minutes) and appears only with intravenous administration. At the same time, the work of the heart increases and blood pressure increases as a result of the release of adrenaline from the adrenal glands and the acceleration of impulses through the sympathetic ganglia. These drugs are indicated for respiratory depression caused by carbon monoxide poisoning, drowning, neonatal asphyxia, brain injury, and for the prevention of atelectasis and pneumonia. However medical significance they are limited. Direct and mixed action analeptics are used more often.
Anticholinesterase drugs: classification, mechanism and features of action, drugs, use and side effects. Clinic of acute poisoning with anticholinesterase drugs, assistance measures
Anticholinesterase drugs, reversibly or irreversibly blocking synaptic acetylcholinesterase and blood pseudocholinesterase, cause the accumulation of acetylcholine, enhance and prolong its effect on M- and N-cholinergic receptors. Cholinesterase has two active centers - anionic(carboxyl glutamic acid) and esterase(histidine imidazole and serine hydroxyl). The cationic head of acetylcholine associates with the anionic center of cholinesterase ionic bond, which ensures recognition of the enzyme by the mediator. Hydrolysis requires a covalent bond between the carbonyl carbon of acetylcholine and the hydroxyl of the esterase center.
There is an excess of acetylcholinesterase in cholinergic synapses, therefore, an increase in cholinergic transmission occurs only when 80 - 90% of the enzyme molecules are inhibited.
The first anticholinesterase drug, the alkaloid physostigmine (eserine), was isolated from Calabar beans in 1864.
Reversible CHOLINESTERASE blockers(physostigmine, proserine, pyridostigmine) are esters of amino alcohols and carbamic acid (H 2 N - COOH). Carbamic acid establishes a covalent bond with the esterase center of cholinesterase, which is much stronger than the bond acetic acid acetylcholine. Hydrolysis of the covalent bond of carbamic acid occurs within 3–4 hours.
Tertiary amines PHYSOSTIGMINE - ester of N-methylcarbamic acid, alkaloid of Calabar beans; GALANTAMINE (NIVALIN, REMINYL) - alkaloid of Voronov's snowdrop tubers; AMIRIDINE (NEUROMIDIN) - a synthetic derivative of quinoline, blocks not only cholinesterase, but also potassium channels of neurons, which prevents the release of potassium ions and facilitates depolarization;
· TACRINE- a synthetic derivative of acridine, the pharmacological action is similar to amiridine, but has hepatotoxicity. Reversible cholinesterase blockers - tertiary amines are well absorbed into the blood when taken orally, inhaled and cutaneously, and inhibit cholinesterase in the central nervous system and peripheral synapses.
Quaternary amines PROZERIN (NEOSTIGMIL) - a simplified analogue of physostigmine, an ester of N-dimethylcarbamic acid, has a strong, quickly onset and short-lasting effect; PYRIDOSTIGMINE BROMIDE (KALIMINE) - a derivative of proserine with a longer lasting effect; DISTIGMINE BROMIDE (UBRETID), OXAZIL, QUINOTILINE are symmetrical bisammonium compounds, superior in activity to proserine.
Quaternary amines have a number of features: they penetrate membranes poorly; do not enter the brain through the blood-brain barrier; weakly alter the functions of cholinergic synapses of internal organs (M-cholinergic receptors) and autonomic ganglia (HH-cholinergic receptors); significantly improve neuromuscular transmission (H M -cholinergic receptors).
Irreversible CHOLINESTERASE blockers have the chemical structure of organophosphorus compounds (OPCs). This pharmacological group includes insecticides and acaricides (karbofos, chlorophos, dichlorvos, metaphos), chemical warfare agents (sarin, soman, tabun) and drugs for the treatment of severe glaucoma (ARMIN). The first organophosphorus substance was synthesized in 1854 - 10 years earlier than it was isolated physostigmine. Phosphorus establishes a very strong covalent bond with the esterase center of cholinesterase, resistant to hydrolysis. Enzyme activity is restored after a few weeks by the synthesis of new molecules. FOS have high lipid solubility and quickly penetrate cell membranes. Some substances in this group are oxidized by cytochrome R-450 liver or hydrolyzed A- esterases (paraoxonase) of blood and liver. A-esterases do not exhibit cholinesterase activity and are resistant to blockers. In the brain, FOS irreversibly inhibits carboxylesterases (aliesterases), which protects acetylcholinesterase. Anticholinesterase drugs not only inhibit cholinesterase, but also directly excite or sensitize cholinergic receptors and facilitate the release of acetylcholine from cholinergic endings. M-cholinomimetic properties are characteristic of physostigmine and armine; galantamine, proserine, pyridostigmine, distigmine, oxazyl and quinotiline have an N-cholinomimetic effect. Selective excitation of cholinergic receptors appears after denervation of organs and degeneration of cholinergic endings. Depolarization of the presynaptic membrane under the influence of excess acetylcholine creates antidromic impulses to the motor neurons of the spinal cord, which is accompanied by fasciculation (lat. fasciculus- bunch muscle fibers) - contraction of motor units of skeletal muscles.
Local action anticholinesterase drugs on the eye similar to the effects of M-cholinomimetics (miosis, decreased intraocular pressure, accommodation spasm), but stronger and longer lasting. When using cholinesterase blockers, pain in the eye, hyperemia of the sclera and conjunctiva are possible; with long-term use, persistent miosis and cataracts develop.
Physostigmine and proserine are used in eye drops to treat severe forms glaucoma. If they are ineffective, the use of Armin is permissible. Galantamine is contraindicated in ophthalmology due to irritating effect. Resorptive effect of anticholinesterase drugs is the algebraic sum of the effects of excitation of M- and N-cholinergic receptors in the central nervous system and peripheral cholinergic synapses. Central effects- improvement of memory and learning (cholinergic transmission to the central nervous system is facilitated). 2. Muscarinic-like effects- decreased heart rate and atrioventricular conduction, arterial hypotension, contraction of smooth muscles, increased secretory function of the glands. 3. Nicotine-like effects- tachycardia, arterial hypertension (indirect stimulation of H-cholinergic receptors of the sympathetic ganglia and the adrenal medulla), shortness of breath (indirect stimulation of H-cholinergic receptors of the carotid glomeruli), increased tone and contractile activity of skeletal muscles.
Related information.
Cholinomimetic agents I
Cholinomimetic drugs (cholino [Receptors] + Greek mimētikos, imitating, reproducing; synonyms: )
drugs that reproduce the effects of stimulation of cholinergic receptors by their natural ligand - acetylcholine. The cholinergic effect can be enhanced both by direct interaction of Ch. with a certain type of cholinergic receptor (direct action cholinergic), and the preservation of excess acetylcholine in the synapse by inhibiting the destruction of it (indirect action cholinergic). In the second case, all types of cholinergic receptors are initiated, incl. localized in the central nervous system and at neuromuscular junctions of skeletal muscles. H. s. indirect action form an independent group of anticholinesterase drugs (Anticholinesterase drugs). H. s. direct action in accordance with the classification of cholinergic receptors (see Receptors) are divided into m-, n- and n+m-cholinomimetics. m-cholinomimetics- aceclidine and pilocarpine - cause local (with local use) or general effects stimulation of m-cholinergic receptors: spasm of accommodation, decrease in intraocular pressure; , slowing of atrioventricular conduction; , increased tone and motility of the gastrointestinal tract, bladder, uterus; liquid saliva, increased secretion of bronchial, gastric and other exocrine glands. All these effects are prevented or eliminated by the use of atropine and other m-cholinergic drugs (see Anticholinergic drugs), which are always used in cases of overdose of m-cholinomimetics, poisoning with substances with a similar or anticholinesterase effect. Indications for the use of m-cholinomimetics: thrombosis of the central retinal vein; stomach, intestines, bladder, uterus, postpartum. General contraindications to their use are angina, myocardial damage, intraatrial and atrioventricular, gastrointestinal bleeding, (before surgery), epilepsy, normal. Aceclidine- (for cooking eye drops in the form of 2%, 3% and 5% aqueous solutions) and 0.2% solution in ampoules of 1 and 2 ml For subcutaneous injections. For glaucoma, instillation is carried out 2 to 6 times a day. For acute atony of the bladder, 1-2 doses are administered subcutaneously ml 0.2% solution; in the absence of the expected result, the injections are repeated 2-3 times with an interval of half an hour, unless undesirable effects are expressed (bronchospasm, bradycardia, etc.). Pilocarpine hydrochloride mainly used in ophthalmological practice. Its main forms of release: 1% and 2% solutions in bottles of 5 and 10 ml; 1% solution in dropper tubes; 1% solution with methylcellulose in bottles of 5 and 10 ml; eye films (2.7 each mg pilocarpine hydrochloride in each); 1% and 2% ophthalmic. Most often, 1% and 2% solutions are used, instilling them into the eye 2 to 4 times a day. n-cholinomimetics- lobeline and cytisine - excite postsynaptic signals in the sympathetic and parasympathetic ganglia nervous system, in the carotid glomeruli and in the chromaffin tissue of the adrenal glands (increased adrenaline secretion). As a result, both adrenergic and cholinergic effects on executive bodies. At the same time, the action of cytisine (cytiton) is dominated by adrenergic peripheral effects (increased, increased heart contractions), while the action of lobeline is dominated by cholinergic effects (bradycardia, decreased blood pressure are possible). Both alkaloids reflexively (from the receptors of the carotid reflex zone) excite the respiratory system and are used mainly as respiratory drugs in cases of acute respiratory arrest (against the background of long-term depression of the respiratory center, the effect is unstable). Their nicotine-like effect became a prerequisite for the use of lobeline (Lobesil tablets) and cytisine (Tabex films and tablets) to facilitate smoking cessation. Their use for this purpose is contraindicated in case of organic diseases of the cardiovascular system, persistent arterial hypertension, angina pectoris, peptic ulcer stomach and duodenum, bleeding. Lobeline hydrochloride- 1% solution in ampoules of 1 ml; tablets 2 mg(drug "Lobesil"). For acute respiratory arrest in adults, 0.3-0.5 is administered ml(children 0.1-0.3 ml depending on age) intramuscularly or intravenously slowly (in 1-2 min), because rapid administration threatens collapse and cardiac arrest. In case of overdose, convulsions, severe bradycardia, and profound respiratory depression are also possible. During the period of quitting smoking, Lobesil is prescribed in the first week, 1 tablet up to 5 times a day, then the frequency of doses is reduced until withdrawal (20-30 days). At poor tolerance(, weakness,) the drug is discontinued. Cititon- 0.15% cytisine solution in ampoules of 1 ml; Tabex tablets and films for cheek (or gum) applications 1.5 mg. Due to its pressor effect, it is used more often than lobeline, because acute respiratory depression often occurs against the background of collapse or shock. Adults are administered intravenously or intramuscularly at 0.5-1 ml(children under 1 G oda - 0.1 each ml). For those quitting smoking general scheme the use of Tabex tablets is the same as for Lobesil tablets; The films are changed 4-8 times in the first three days, then 3 times a day, from the 13th to the 15th day 1 film is used, then discarded. n+m-cholinomimetics are represented by acetylcholine (a drug), which is practically not used in medical practice, and carbacholine, which is similar in chemical structure. Carbacholine is not destroyed by cholinesterase and has a longer-lasting and more pronounced cholinergic effect. The overall effect is dominated by the effects of excitation of m-cholinergic receptors, and only against the background of their blockade do n-cholinergic effects clearly appear. At the same time, carbocholine has no advantages over drugs from the m-cholinomimetics group, therefore, of the previously known forms of its release, only ophthalmic ones have been retained and are practically used (in the form of 0.75%, 1.5%, 2.25% and 3% r- carbacholine) for the treatment of glaucoma. During eye surgeries, sometimes 0.5 is injected into the anterior chamber of the eye to narrow the pupil. ml 0.01% carbacholine solution. cholinergic drugs with different mechanisms of action, causing effects characteristic of excitation of cholinergic receptors. M-cholinomimetic drugs(syn.: M-cholinomimetics, M-cholinergic drugs) - X. s., stimulating or promoting the excitation of M-cholinergic receptors (pilocarpine, aceclidine, etc.) N-cholinomimetic drugs(syn.: H-cholinomimetics, H-cholinergic drugs) - X. s., stimulating or promoting the excitation of H-cholinergic receptors (lobeline, cytisine, etc.). 1. Small medical encyclopedia. - M.: Medical encyclopedia. 1991-96 2. First health care. - M.: Great Russian Encyclopedia. 1994 3. Encyclopedic Dictionary of Medical Terms. - M.: Soviet Encyclopedia. - 1982-1984.
See what “cholinomimetic drugs” are in other dictionaries:
Medicinal substances whose effect is similar to the effect of excitation of cholinergic receptors of the body’s biochemical systems with which acetylcholine reacts (for example, pilocarpine) ... Big Encyclopedic Dictionary
Pharmacological substances of various chemical structures, the action of which basically coincides with the effects of excitation of cholinergic nerve fibers (See Cholinergic nerve fibers) or the mediator Acetylcholine. By… …
Medicinal substances whose effect is similar to the effect of excitation of cholinergic receptors of the body's biochemical systems with which acetylcholine reacts (for example, pilocarpine). * * * CHOLINOMIMETIC DRUGS CHOLINOMIMETIC DRUGS,… … encyclopedic Dictionary
- (choline-positive, or cholinergic drugs), lec. in VA, according to pharmacological St you are close to the neurotransmitter acetylcholine, i.e. interacting with cholinergic receptors and causing cholinergic excitation. endings of nerve fibers. Due to... ... Chemical encyclopedia
- (cholinomimetica; choline + Greek mimetikos capable of imitating, imitating; synonym: cholinomimetics, cholinergic drugs) cholinergic drugs with a different mechanism of action, causing effects characteristic of excitation... ... Big medical dictionary
CHOLINOMIMETICS- cholinomimetics, drugs. substances that act like acetylcholine on cholinoreactive synaptic systems. According to its ability to act on muscarine or nicotine-sensitive synapses X. p. are divided into m cholinomimetics (arecoline hydrobromide... Veterinary encyclopedic Dictionary
- (syn.: M cholinomimetics, M cholinergic drugs) X. s., stimulating or promoting the excitation of M cholinergic receptors (pilocarpine, aceclidine, etc.) ... Large medical dictionary
- (syn.: H cholinomimetics, H cholinergic drugs) X. s., stimulating or promoting the excitation of H cholinergic receptors (lobelia, cytisine, etc.) ... Large medical dictionary
Anticholinergics, pharmacological substances, blocking the transmission of excitation from cholinergic nerve fibers (See Cholinergic nerve fibers), antagonists of the mediator acetylcholine. Belong to different groups... ... Big Soviet encyclopedia
- (anticholinergic, anticholinergic, anticholinergic), medication. in va, warning, weakening and stopping interaction. neurotransmitter acetylcholine and cholinomimetic. drugs with cholinergic receptors. Due to the presence in the central and peripheral... ... Chemical encyclopedia
Subgroup drugs excluded. Turn on
Description
Drugs in this group reproduce the effects of the parasympathetic nervous system mediator, acetylcholine, due to its interaction with m-cholinergic receptors. m-cholinergic receptors are localized in all organs receiving parasympathetic innervation, at the end of postganglionic parasympathetic fibers. m-cholinergic receptors are heterogeneous. Interaction with m 1 -cholinergic receptors of the central nervous system is accompanied by the occurrence of excitation, and with m 1 -receptors of the intramural parasympathetic plexuses of the gastrointestinal tract - an increase in the secretion of gastrointestinal glands.
The effect of activation of m 2 -cholinergic receptors localized in the heart is manifested in a decrease in heart rate and other cardiac functions, incl. conductivity.
The most numerous effects of m-cholinomimetics are due to the stimulation of m 3 -cholinergic receptors of smooth muscles and exocrine glands. They cause bronchospasm and bronchorrhea, increased secretion of the gastric glands, increased tone of the gastrointestinal tract, bile and urinary tract. The effect of aceclidine on the gastrointestinal tract can be used for intestinal and bladder atony.
The most relevant aspect of the pharmacodynamics of m-cholinomimetics is their effect on intraocular pressure: they improve the outflow of intraocular fluid and, thereby, lower intraocular pressure. This effect is used in the treatment of intraocular hypertension and glaucoma.
Drugs
Drugs - 222 ; Trade names - 12 ; Active ingredients - 1
| Active substance | Trade names |
| Information is absent | |
7. N-cholinomimetic drugs. The use of nicotine mimetics to combat smoking.
Localization of Hn-cholinergic receptors and pharmacological effects upon their stimulation.
Localization: neuronal ganglia of the ANS, adrenal medulla, neurons of the central nervous system
Pharmacological effects when stimulated:
1) excitation of the neuronal ganglia of the ANS (sympathetic more than parasympathetic)
2) CVS: tachycardia, vasospasm, hypertension
3) Gastrointestinal tract, MPS: 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.
a) short-acting – trepirium iodide (hygronium);
b) average duration of action - hexamethonium benzosulfonate (benzohexonium), azamethonium bromide (pentamine);
c) long-acting – pempidine (pyrylene).
Place of action on the PNS diagram: ANS ganglia, adrenal medulla, central nervous system.
mechanisms of action and pharmacological effects of N-cholinomimetics.
Mechanism of action: excitation of N-Chr. The initial effect is stimulation of H-Chr, the long-term effect is a depolarization block.
Pharmacological effects of N-cholinomimetics:
1) stimulation of the autonomic ganglia (sympathetic more 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 useN-cholinomimetics.
Indications:
smoking cessation relief
reflex cessation of breathing (during operations, injuries, etc.)
shock and collaptoid states (pressor effect), respiratory and circulatory depression in patients with infectious diseases.
Contraindications:
atherosclerosis
marked increase in blood pressure
erosive and ulcerative lesions of the gastrointestinal tract in the acute phase, bleeding from large vessels
pulmonary edema
pregnancy.
LOBELIN (Lobelinum).
Lobeline racemate is obtained synthetically.
In medical practice, lobeline 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.
Lobeline 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 effect of lobeline is accompanied by stimulation of the respiratory and other centers of the medulla oblongata. In connection with the stimulation of breathing, lobeline was proposed as an analeptic agent for use in reflex respiratory arrests (mainly when inhaling irritants, carbon monoxide poisoning, etc.).
Due to the simultaneous stimulation of the vagus nerve, lobeline causes a slowdown in heart rate and a decrease in blood pressure. Later arterial pressure may increase slightly, which depends on vasoconstriction caused by the stimulating effect of lobeline on the sympathetic ganglia and adrenal glands. In large doses, lobeline stimulates the vomiting center, causing deep respiratory depression, tonic-clonic convulsions, and cardiac arrest.
Recently, lobeline has been used extremely rarely as a respiratory stimulant. If breathing weakens or stops, developing as a result of progressive depletion of the respiratory center, the administration of lobeline is not indicated.
Lobeline is used as an injection intravenously, less often intramuscularly.
Lobeline is administered intravenously slowly (1 ml over 1 - 2 minutes). With rapid administration, temporary cessation of breathing (apnea) sometimes occurs and side effects from the cardiovascular system (bradycardia, conduction disturbances) develop.
Lobelin is contraindicated in acute organic diseases of the cardiovascular system.
Lobelin and others similar in action<<ганглионарные>> substances (cytisine, anabasine) have found use in recent years as smoking cessation aids. Tablets containing lobeline are available for this purpose under the name<<Лобесил>> (Tabulttae "Lobesilum").
The tablets are coated (cellulose acetylphthalyl cellulose), which ensures the passage of the drug unchanged through the stomach and its rapid release in the intestines.
Use of tablets<<Лобесил>>, as well as tablets and other medicines containing cytisine and anabasine hydrochloride, reduces the desire to smoke and alleviates the painful phenomena associated with smoking cessation for smokers.
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 also 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 - 4 weeks with a gradual decrease in the frequency of administration. In case of relapses, the course of treatment can be repeated.
The use of tablets with lobeline, cytisine and anabasine is contraindicated in case of exacerbation of gastric and duodenal ulcers, sudden organic changes in cardiovascular system. Treatment should be carried out under the supervision of a physician. In case of overdose, side effects are possible: weakness, irritability, dizziness, nausea, vomiting.
CITIZIN (Cytisinum).
Cytisine is an alkaloid found in the seeds of broom (Cytisus laburnum L.) and thermopsis (Thermopsis lanceolata, R. Br.), both from the legume family (Leguminosae).
Refers to substances<<ганглионарного>> actions and in connection with the stimulating effect on breathing is considered as a respiratory analeptic. For this purpose, it is available in the form of a ready-made 0.15% aqueous solution called<<Цититон>> (Cytitonum).
In recent years, cytisine has also begun to be used as a smoking cessation aid (see tablets<<Лобесил>>) .
Cytisine has an exciting effect on the ganglia of the autonomic nervous system and related formations: chromaffin tissue of the adrenal glands and carotid glomeruli.
Characteristic of the action of cytisine (as well as lobeline) is the excitation of breathing associated with reflex stimulation of the respiratory center by enhanced impulses coming from the carotid glomeruli. Simultaneous stimulation of the sympathetic nodes and adrenal glands leads to an increase in blood pressure.
The effect of cytiton (cytisine solution) on breathing is short-term<<толчкообразный>> character, however, in some cases, especially with reflex cessation of breathing, the use of cititon can lead to a permanent restoration of breathing and blood circulation.
Previously, cititone was widely used for poisoning (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, cititon and lobeline currently have limited use. Nevertheless, in case of reflex cessation of breathing (during operations, injuries, etc.), tsititon can be used as a respiratory analeptic; Due to the pressor effect (which distinguishes it from lobeline), cititone can be used in shock and collaptoid conditions, in respiratory and circulatory depression in patients with infectious diseases, etc.
Cititon is administered into a vein or intramuscularly. Most effective intravenous administration. If indicated, the injection of cititon can be repeated after 15 - 30 minutes.
Cititon was previously also used to determine blood flow velocity. The method consists of determining the time that elapses from the moment of injection of cititon into the antecubital vein until the appearance of the first deep breath. The determination is more demonstrative than with the administration of lobeline, since the excitation of breathing is more clearly expressed and changes in breathing are easy to register. Usually 0.7 - 1 ml of tsititon is administered for this purpose (0.015 ml per 1 kg of patient body weight).
Cititon is contraindicated (due to its ability to increase blood pressure) in cases of severe atherosclerosis and hypertension, bleeding from large vessels, and pulmonary edema.
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 anabasine.
Use of tablets<<Табекс>> must be carried out as directed and under the supervision of a physician. In case of an overdose, nausea, vomiting, dilated pupils, and increased heart rate are possible, which requires stopping the drug.
Films with cytisine (Membranulae cum Cytisino) are also produced. Oval-shaped polymer plates with blunted 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 gums or mucous membrane of the cheek area every day for the first 3 to 5 days, 4 to 8 times.
If the effect is positive, 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 12th day, 1 film 2 times a day, from the 13th to 15th 1st 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 cases of bleeding, severe hypertension, and advanced stages of atherosclerosis.
ANABAZINE HYDROCHLORIDE (Anabasinum hydrochloridum).
Anabasine is an alkaloid found in the plant Anabasis aphylla L. (barnyard grass), fam. goosefoot (Chenopodiaceae).
Chemically it is 3-(piperidyl-2) pyridine.
Its pharmacological properties are similar to nicotine, cytisine and lobeline.
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>> .
Take tablets with anabasine hydrochloride orally or sublingually daily. From the first day of taking the pills, you must stop smoking or sharply reduce its frequency and completely stop smoking no later than 8-10 days from the start of treatment.
If the desire to smoke does not decrease within 8-10 days, stop taking the pills and make a new attempt at treatment after 2-3 months.
Tablets are contraindicated for atherosclerosis, severe increases in blood pressure, and bleeding.
In the first days of taking the pills, nausea, headache and increased blood pressure are possible. Usually these phenomena disappear when the dose is reduced. If necessary, stop taking the pills.
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). Polymer oval-shaped plates of white (or with yellowish tints) color, dimensions 9 X 4.5 X 0.5 mm, containing 0.0015 g (1.5 mg) of anabasine hydrochloride. They are also intended for smoking cessation.
The film is glued to the gum of the labial part or the mucous membrane of the buccal area every day for the first 3 to 5 days, 4 to 8 times.
From the first day of treatment, it is advisable to stop smoking or sharply reduce the frequency of smoking.
In the first days of using film with anabasine hydrochloride, unpleasant taste sensations, nausea, mild headache, dizziness, and a slight increase in blood pressure are possible. In these cases, you should stop using the drug.
Gamibasin (Gamibasinum). Chewing gum(based on a special chewing mass) containing 0.003 g of anabasine hydrochloride.
A rectangular or square elastic band (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, lemon acid, flavoring, etc.).
Is one of dosage forms Anabasine for smoking cessation. Apply by prolonged chewing daily, initially 1 gum (0.003 g) 4 times a day for 4 - 5 days. If the effect is positive, treatment is continued according to the following scheme: from the 5th - 6th to the 8th day - 1 rubber band 3 times a day; from the 9th to the 12th day - 1 elastic band 2 times a day; further until the 20th day - 1 rubber band 1 - 2 times a day. Subsequent courses may be repeated.
| " |
M-cholinomimetics have a direct stimulating effect on M-cholinergic receptors. The standard for such substances is the alkaloid muscarine, which has a selective effect on M-cholinergic receptors. Muscarine is not a medicine, and the poison contained in fly agaric mushrooms can cause acute poisoning.
Muscarine poisoning produces the same clinical picture and pharmacological effects as AChE agents. There is only one difference - here the effect on M-receptors is direct. The same basic symptoms are noted: diarrhea, difficulty breathing, abdominal pain, salivation, constriction of the pupil (miosis - the circular muscle of the pupil contracts), decreased intraocular pressure, a spasm of accommodation (near point of vision), confusion, convulsions, coma.
From M-cholinomimetics to medical practice the most widely used are: PILOCARPINE HYDROCHLORIDE (Pilocarpini hydrochloridum) powder; eye drops 1-2% solution in bottles of 5 and 10 ml, eye ointment - 1% and 2%, eye films containing 2.7 mg of pilocarpine), ACECLIDINE (Aceclidinum) - amp. - 1 and 2 ml 0 .2% solution; 3% and 5% - eye ointment.
Pilocarpine is an alkaloid from the shrub Pilocarpus microphyllus, ( South America). Currently obtained synthetically. Has a direct M-cholinomimetic effect.
By stimulating effector organs that receive cholinergic innervation, M-cholinomimetics cause effects similar to those observed when irritating autonomic colinergic nerves. Pilocarpine especially strongly increases the secretion of glands. But pilocarpine, being a very strong and toxic drug, is used only in ophthalmic practice for glaucoma. In addition, pilocarpine is used for thrombosis of retinal vessels. Use topically, in the form of eye drops (1-2% solution) and eye ointment (1 and 2%) and in the form of eye films. It constricts the pupil (3 to 24 hours) and reduces intraocular pressure. In addition, it causes a spasm of accommodation. The main difference from AChE agents is that pilocarpine has a direct effect on M-cholinergic receptors of the eye muscles, and AChE agents have an indirect effect.
ACECLIDINE (Aceclidinum) is a synthetic direct-acting M-cholinomimetic. Less toxic. They are used for local and resorptive action, i.e. they are used both in ophthalmic practice and for general effects. Aceclidine is prescribed for glaucoma (slightly irritates the conjunctiva), as well as for gastrointestinal atony (in postoperative period), bladder and uterus. At parenteral administration There may be side effects: diarrhea, sweating, drooling. Contraindications: bronchial asthma, pregnancy, atherosclerosis.
Drugs that block m-cholinergic receptors (m-cholinergic blockers, 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 M-cholinergic receptors located on the membrane of effector cells at the endings of postganglionic cholinergic fibers, i.e., they block PARASYMPATHETIC, 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, i.e. chemically. The name Atropa Belladonna is paradoxical, since the term "Atropos" means "three destinies leading to an inglorious end of life", and "Belladonna" means "charming woman" (donna - woman, Bella - 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:
1) 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 preservation of the sympathetic innervation of the m.dilatator pupillae. Therefore, atropine acts on the eye for a long time in this regard - up to 7 days;
2) 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);
3) relaxation of the ciliary muscle and displacement of the lens into the anterior chamber of the eye is accompanied by a violation of the outflow of intraocular fluid from the anterior chamber. In this regard, atropine either does not change intraocular pressure in healthy individuals, or in individuals with a shallow anterior chamber and in patients with narrow-angle glaucoma, it may even increase, i.e., 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, i.e. 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 EXTERNAL SECRETION GLANDS. Atropine sharply weakens the secretion of all exocrine glands, with the exception of mammary glands. In this case, atropine blocks the secretion of thin, watery saliva caused by stimulation parasympathetic division autonomic nervous system, dry mouth occurs. Tear production decreases. Atropine reduces the volume and overall acidity of gastric juice. In this case, suppression and weakening of the secretion of these glands can be up to their complete shutdown. Atropine reduces the secretory function of glands in the cavities of the nose, mouth, pharynx and bronchi. The secretion of the bronchial glands becomes viscous. Atropine, even in small doses, inhibits the secretion of SWEAT GLANDS.
5) INFLUENCE OF ATROPINE ON THE CARDIOVASCULAR SYSTEM. Atropine, removing the heart from the control of n.vagus, causes TACHYCARDIA, i.e. 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 n.vagus tone. 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:
1) intestinal
2) renal
3) hepatic colic.
2) For bronchospasms (see adrenergic agonists).
3) B complex therapy patients with peptic ulcer of the stomach and duodenum (reduces the tone and secretion of the glands). Used only in combination therapeutic activities, since secretion is reduced only in large doses.
4) As a premedication agent in anesthesiological practice, atropine is widely used before surgery. Atropine is used as a means of drug preparation of a patient for surgery 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, the development of inflammatory postoperative complications in the lungs is prevented. 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, i.e., bradycardia and heart block).
6) Atropine has found widespread use as an ambulance 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 scopolamine (0.3-0.6 mg s.c.) as a premedication, but usually in combination with morphine (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, increased tone cerebral 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 dilation of the pupil and paralysis of accommodation, i.e. 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 IOP elevation is less, because weaker than atropine, but at the same time, the drug is contraindicated in 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 does not penetrate well through the BBB. This means that all its effects are due to peripheral M-anticholinergic action. 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 (i.v. - in 5-10 minutes, intramuscularly - in 30 minutes) - more convenient than atropine. It has an analgesic effect superior to atropine and 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 in 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 broad pharmacological action of the drugs being studied and are manifested by dry mouth, difficulty swallowing, intestinal atony (constipation), visual perceptions, tachycardia. Topical use of atropine may cause allergic reactions(dermatitis, conjunctivitis, swelling of the eyelids). Atropine is contraindicated in 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 these symptoms, PSYCHOMOTOR EXCITATION comes to the fore, i.e., both mental and motor excitement. From here famous expression: “I ate 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 orally, then an attempt should be made to pour it out 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 and 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 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 with cool water. Careful care is required. Artificial respiration is often required.
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. 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 neuromuscular junctions, CNS.
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.
Loading...