Anticholinesterase agents

Anticholinesterase agents - the substances which inhibit the activity of cholinesterase - enzymethat breaks down acetylcholine.
To the anticholinesterase means are physostigmine, galantamine, neostigmine, oksazil, fosfata, Armin, piropos and other
In the presence of anticholinesterase means slowing the destruction of acetylcholine (see), it accumulates and causes the appropriate action: narrowing of a pupil, downturn intraocular pressure, drowsiness, increased peristalsis of the bowel, slow heart rate, strengthening of the uterus and other
Anticholinesterase agents most often used in glaucoma as a means of narrowing a pupil and decreasing the intraocular pressure. Physostigmine, neostigmine, galantamine, oksazil used with flaccid paralysis, myasthenia. The therapeutic effect in these cases, due to the improvement of impulses in the synapses of the Central and peripheral nervous system. The use of anticholinesterase means contraindicated in epilepsy, the giperkineza, bronchial asthma, the expressed atherosclerosis, stenocardia.
Symptoms of poisoning antiholinesteraznami means: severe headache, shortness of breath, narrowing pupils, abdominal pain, diarrhea, strong salivation and sweating, severe poisoning - convulsions, loss of consciousness. Death can occur from respiratory arrest.
First aid - 3-4 ml of 0.1% solution of atropine subcutaneously or intravenously. Also effective amizil (see), tropatsin (see); apply reaktivatory cholinesterase (2-PAM, and other). Disorders of breathing - artificial respiration. Separate anticholinesterase agents - see Art. name drugs (Armin, Galantamine and others).

Antiholinesteraznae means - group substances inhibit the activity of cholinesterase enzyme that breaks down acetylcholine (acetylcholinesterase, cholinesterase). The inhibition of acetylcholinesterase activity, which is contained in the nervous system, red blood cells and in many tissues, leading to the accumulation of acetylcholine (see) in the synapses, where he is the mediator of nervous excitement. Thus there is the excitement of all cholinergic systems. When toxic doses antiholinesteraznah funds after the excitation may be a violation of holding in the cholinergic synapses. Cholinesterase contained in the blood plasma and in some tissues; activity it can be slowed down almost completely without serious violations of the physiological functions of the organism.
Antiholinesteraznae funds are divided into two large groups on the reversibility of their oppressive actions. Antiholinesteraznae means reversible action [ezerin (see Fizostigmina, galantamina (see), neostigmine (cables) and others] are connected with the same reactive points of the active surface of enzyme - anionic and asterichesky, interacts and acetylcholine. When this enzyme is losing the ability to connect with acetylcholine and split it. Oppression is of a competitive nature. Themselves anticholinesterase agents (ezerin, neostigmine), too, is hydrolyzed by cholinesterase, but much (in thousands of times slower than acetylcholine. After the destruction or removal antiholinesteraznah funds reversible actions, the ability of cholinesterase to break down acetylcholine is fully restored.
The group antiholinesteraznah funds, irreversibly oppressive cholinesterase, are derivatives of phosphorous and phosphinic acid - organophosphorus substances [fosfata (see), Armin (see), piropos (see) and others]. When interacting with cholinesterase part molecules such A. C. firmly attached to asterichesky paragraph, forming phosphorylated enzyme, unable to break down acetylcholine. The possibility to reactivate phosphorylated enzyme using Akimov (so-called the reaktivatory): pyridine-2-alcoxylate (2 PM), diacetylmonooxide (LADIES), 1,3-bis-(N-pyridine - 4-aldoxime) - propargylamine (TMB-4).
Under the action of many of organophosphorus substances in the organism, the activity of cholinesterase (without the use of reaktivatory) to recover almost only by the synthesis of a new enzyme. This is related to the duration of these A. S. and cumulation of their actions. Serum cholinesterase is synthesized in the liver. Its activity, reduced organophosphorus antiholinesteraznami means is restored within a few weeks, but with liver disease process can be very slow. The restoration of activity of erythrocyte acetylcholinesterase is the same rate as their regeneration, and acetylcholinesterase brain and muscles can only be achieved in a few months.
Some substances used in connection with their anticholinesterase action outside the body does not inhibit cholinesterase and only in the body turn into A. S. these Are, for example, octamethylcyclotetrasiloxane (OMPA), parathion, systox.
Effect antiholinesteraznah funds to different systems and organs is mainly determined by their ability to protect the acetylcholine from destruction. Therefore, it is usually the same as the effects of excitation of cholinergic nerves and to a large extent depends on their tonus. So, ezerin not big eyeball in the dark when oculomotor nerve not toned and end to end, not allocated acetylcholine. Action A. S. on bodies with the cholinergic innervation not develop after their denervation. Some A. S., apparently, can be toxic in high doses to show and direct holinomimeticescoe effect, especially on the n-holinoreaguykh systems.


Anticholinesterase agents cause narrowing of a pupil, downturn intraocular pressure and accommodation spasm, increase motility and partly gland secretion of gastrointestinal tract increases the contractions of the uterus and bladder, increase the bronchial tone muscles, increased secretion of the glands with the cholinergic innervation (salivary, tearful, sweat, mucous glands of the respiratory tract). Effect antiholinesteraznah funds on the cardiovascular system is less certain, as they raise the tone not only parasympathetic, but sympathetic nerves, affecting cholinergic the transfer of excitation in the nerve, and increase the secretion of adrenalin brain substance napochechnikov. On the Central nervous system A. S. usually provide a stimulating, exciting action, which, apparently, is also connected with stabilization of acetylcholine at the cholinergic synapses of the Central nervous system, as the Central effects A. S. removed anticholinergic agents. The Central action is especially strongly expressed in A. E., well-soluble in lipids (ezerin, galantamine).
A. S. widely used in medicine. Glaucoma drops A. S. eyes reduces inner pressure. A. S. also used for prevention and treatment of postoperative atony bowel and bladder. Neostigmine is used to accelerate delivery with the weakness of contractile activity of the uterus. For diagnosis and treatment mvastenia gravis used galantamine, neostigmine. A. S. is used for rehabilitation therapy for diseases of the Central nervous system. Neostigmine, galantamine, ezerin used as an antidote for poisoning anticholinergic agents (atropine, curare and others) as their physiological antagonist. In a joint application of different antiholinesteraznah funds should be aware that organophosphorus A. S. for a few days and increase sensitivity to A. S. reversible action type prozerina. On the contrary, after prozerina sensitivity to organophosphorus A. S. reduced. A. S. contraindicated in epilepsy, giperkineza, bronchial asthma, stenocardia expressed arteriosclerosis. They are used for physiological analysis of the role of acetylcholine and cholinesterase in norm and pathology.
Organophosphorus anticholinesterase agents (piropos, AMPA, systox and other) are widely used as insecticides for control of pests of agriculture.
The main symptoms of poisoning A. S. are: reduced pupil (especially when the effects of vapors of volatile A. S. on unprotected eyes), severe headache, shortness of breath due to spasm of the bronchi, stomach pain, diarrhea, drowsiness, fastsikulyarny twitching of voluntary muscles, difficulty speaking, the excitement, the feeling of fear. In severe poisoning - strong choking, General convulsions, loss of consciousness, vomiting, involuntary urination and defecation. Death occurs from respiratory arrest; it may be associated with paralysis of the respiratory centre, severe bronchospasm, and in violation of the procedure of nerves on the respiratory muscles. In chronic poisoning A. S. at the forefront are the narrowing of a pupil, headaches, occasional difficulty breathing, weakness, irritability. The objective criterion of severity of poisoning is the decrease of activity of cholinesterase (especially acetylcholinesterase) blood in chronic poisoning by 25-50%, and in acute - stronger (when death by accidental poisoning Perfocom - 90%).
Acute poisoning antiholinesteraznami means the main antidote are anticholinergic agents. The positive effect gives the re-introduction of atropine under the skin to 0,002 grams (!) before the emergence of feelings of dryness in the mouth. More effective antidotes are: amizil (see), tropatsin (see) and other synthetic anticholinergic agents. Substantial assistance can provide artificial respiration and intravenous reaktivatory: 2 AM, LADIES (2000 mg), TMB-4 (250 mg).