Cholinomimetics

Cholinomimetics (holinomimetiki) - substances which excite holinoretseptora - biochemical systems of the body that reacts acetylcholine. Holinoretseptora are not homogeneous. Some of them are selective sensitivity to nicotine and are called nicotine-sensitive, or n-holinoretseptorami. n-holinoretseptora are in the ganglion of the sympathetic and parasympathetic nerves, brain substance napochechnikov, karotidnykh clubockah, the motor nerves endings in Other CNS acetylcholine receptors selective sensitivity to muscarine - alkaloid isolated from toadstools. Therefore they are called muskarinochuvstvitelnye, or m-holinoretseptorami. m-Holinoretseptora are endings postganglionarnyh parasympathetic (cholinergic) nerve fibers, as well as in the Central nervous system.
Depending on influence on those or other cholinergic receptors are three groups of cholinomimetic funds: 1) n-cholinomimetics - substances, mainly stimulating n-holinoretseptora: lobelin (see), Sahalin (see), tsititon (see); 2) m-cholinomimetics - substances, mainly exciting m-holinoretseptora: aceclidine (see), Bensimon (see), pilocarpine (see); 3) substances which excite both n-and m-holinoretseptora: antiholinesteraznae funds (see), karbaholin (see).
n-cholinomimetics excite breath and increase blood pressure. They are used mainly for extra stimulation of respiration.
m-cholinomimetics enhance the secretion of digestive, and bronchial glands; a slow heart rate; expands blood vessels, lower blood pressure; cause the reduction of smooth muscles of the gastrointestinal tract, bronchi, cholelithiasis and urinary tract; narrow down the pupil and cause spasm of accommodation. m-Holinomimeticalkie means used mainly for the treatment of glaucoma. Constriction of the pupil caused by these substances, leads to lower intraocular pressure.
The effects of substances that excite m - and n-holinoretseptora, largely similar to the effects m-holinomimeticakih funds. This is because the excitement n-holinoretseptorov masked simultaneous excitation m-holinoretseptorov. Among the substances relating to the m - and n-holinomimetikov, wide therapeutic use are only anticholinesterase agents.
Poisoning m - and n-holinomimeticalkie means is characterized by a sharp increase in the secretion of saliva, perspiration, diarrhea, narrowing pupils, slow pulse (in case of poisoning antiholinesteraznami means is more frequent), fall in blood pressure, asthma breathing. The treatment of poisoning is reduced to the introduction of atropine (2 ml of 0.1% solution intravenously) or other holinoliticakih (see).

Cholinomimetics (holinomimetiki) - substances that mimic the action of acetylcholine and providing for the authority's work the same effect as irritation cholinergic nerves that Innervate the body.
Some cholinomimetics (nicotineonline substances) are affected predominantly or exclusively nikotinochuvstvitelnye holinoretseptora. These include nicotine, lobeline (see), tsitizin, anabasine, Sahalin (see).
Mainly on muskarinochuvstvitelnye holinoretseptora act: muscarin, arcolin, aceclidine (see), Bensimon (see), pilocarpine (see), karbaholin (see) - effectiveness of substance.
The mechanism of action holinomimetikov is the same as the mechanism of action of acetylcholine (see)released at the end cholinergic nerves or input from outside. As acetylcholine, holinomimetiki contain a molecule positively charged nitrogen atom - Quaternary, fully ionized (butyrylcholine, Mihail, carbazole, Bensimon, muscarin, Sahalin) or tertiary, usually highly ionized (nicotine, arcolin, aceclidine, pilocarpine, lobelin).
In addition, in the molecule holinomimetikov there is usually ester or another group, creating in the molecule holinomimetikov same distribution of electronic density in a molecule acetylcholine. Due to the similarity of acetylcholine on chemical reactivity cholinomimetics interact with the same areas of activity of surface receptor that react acetylcholine: positively charged nitrogen is connected with the anionic, broadcasting group (or group with similar distribution of electrons) with astrofili part of the receptor. Interaction holinomimetikov with the receptor increases cell membrane permeability to ions. Occurs membrane depolarization, there is a potential actions. In certain organs (such as the heart) holinomimetikami, as acetylcholine, not cause depolarization, and hyperpolarization. This leads to the suppression of the activity of the pacemaker of the heart, slowing heart rate. Unlike acetylcholine, many holinomimetiki not destroyed by cholinesterase.
Nicotineonline and effectiveness substances cause when introduced into the body varies, and sometimes even opposite effects. So, nicotineonline substances increase blood pressure, and lower effectiveness.
Action nicotineonline substances consists of excitation nikotinochuvstvitelnye of holinoretseptora vegetative gangliev, adrenal glands, vascular reflex zones (sinocarotidna and others). The main symptoms of actions nicotineonline substances in case of introducing them in the body are the initiation of breath coming due to reflex excitation holinoretseptorov sinocarotidna zone, and the rise in blood pressure caused by increased secretion of adrenalin adrenal stimulation of sympathetic ganglia, and pressorne reflex with karotidnykh clubockov. Substances containing secondary or tertiary nitrogen atom in the molecule (nicotine, lobelin, tsitizin, anabasine), affect the Central
holinoretseptora: cause the reaction activation on EEG, stimulate higher nervous activity, increase the production of the hormones of the posterior lobe of the pituitary. When large doses are observed tremor and convulsions. Substances containing Quaternary nitrogen atom in the molecule (Sahalin and its homologues, karbaholin), does not have a Central action, so as not penetrate the blood-brain barrier.
For nicotineonline substances characteristically, in their effect on holinoretseptora after excitation occurs blocking receptors, which become insensitive as to acetylcholine and holinomimeticakih means. The exception is Sahalin. It is possible that the lack of "political" phase when it is the action explained partly by the fact that he quickly destroyed cholinesterase.
Effectiveness substances stimulate holinoretseptora receiving pulses from postganglionarnyh cholinergic nerves. Reproduce the effects of excitation of the parasympathetic nervous system. Cause the reduction circular muscle iris, narrowing pupils, reduction of intraocular pressure, spasm of accommodation. Enhance the secretion of glands salivary, tearful, gastrointestinal tract and mucous glands of the respiratory tract. Increase the tone and irritative stomach and intestines; increase the tone and cause reduction of the bladder and uterus. Cause the slower pace and reducing the force of heart contractions, shortening refrakternogo period and infringement on the beam of GIS; cause expansion of blood vessels, especially the skin. Affecting the heart and blood vessels, they cause a marked hypotensive effect. Effectiveness of substance with tertiary nitrogen in the molecule (arcolin, aceclidine) excite and Central muskarinochuvstvitelnye holinoretseptora. Thus observed the reaction activation on EEG, accelerating the development of conditioned reflexes; in high doses, there tremor Central origin.


Some nicotineonline substances used as stimulators of breath when his reflex stop; respiratory depression caused by drug overdose during anaesthesia, poisoning barbiturates and analgesics, carbon monoxide, etc.; to enhance ventilation in the postoperative period for the prevention of pneumonia; to combat asphyxia newborns. As the breathing pacemaker Sahalin has advantages over lobelina and tsititonom as deprived of the Central (side) actions quickly destroyed cholinesterase, and is the second, blocking phases of activity. Due to the large therapeutic latitude of Sahalin you can enter not only intravenously and subcutaneously. Lobelin and tsititon can only be entered intravenously, as in a subcutaneous they in therapeutic doses does not effective.
Effectiveness substances used in the clinic mainly for the same reasons that anticholinesterase: as mioticescimi means - to reduce intraocular pressure in glaucoma and other eye diseases; to combat atony bowel and bladder in the postoperative period; in case of poisoning cholinergic substances as physiological antagonist. Holinomimetiki are usually weaker than anticholinesterase agents, and not so long. Karbaholin use sometimes with paroxysmal tachycardia.
Contraindicated nicotineonline substances for high blood pressure and diseases, in which the increase of pressure is undesirable (expressed cardiovascular pathology, swelling lungs, severe atherosclerosis). Effectiveness of the substance is contraindicated in bronchial asthma, severe organic heart disease, strokes, bleeding from the gastrointestinal tract, pregnancy.
Side effects nicotineonline substances is to increase blood pressure and, in the case of application lobelina and tsitizina - also in the Central effects: may cause nausea, dizziness. Effectiveness substances can cause salivation, sweating, diarrhea, redness of skin, the pressure drop.
Poisoning nicotineonline substances is manifested in the increase of pressure, increased respiration, heartbeat; lobelin and tsitizin can cause dizziness, nausea, vomiting. In the administration of sahalina (at 50-fold increase in therapeutic doses), there may be respiratory failure due to paralysis of the respiratory muscles. Antagonists nicotineonline substances are ganglioblokirtee and sympatholytic agents. Poisoning Maccarinelli is manifested in the excitation of the parasympathetic system: sharp narrowing pupils, lacrimation, increased secretion of the glands, slow heartbeat, expansion vessels, a drop in blood pressure, causes smooth muscles bronchi and intestines, and bladder. All these phenomena are easily removed atropine and other muscarinics substances.