The transmission of impulses through neurons is provided thanks to special substances - mediators. One of the neurotransmitters is acetylcholine. These substances, being in synapses, affect cell membranes, causing their inhibition or excitation and causing various effects. Excess neurotransmitters are broken down by special enzymes.
Anticholinesterase drugs: properties and purpose
Anticholinesterase drugs are those that inhibit the enzyme cholinesterase. This enzyme breaks down by hydrolysis the neurotransmitter acetylcholine, which ensures the transmission of impulses in synapses of parasympathetic nerves sensitive to it, ganglia and in all somatic fibers. Anticholinesterase agents have been developed to situationally enhance the action of acetylcholine on neurons and stimulate certain parts of the nervous system. The use of these drugs has an effect on the entire body as a whole.
The action of anticholinesterase drugs is similar to the effect of stimulation of cholinergic nerves. These drugs interact with the same site of activity on the receptor surface as acetylcholine, thereby creating a nerve ending action potential. Cholinomimetics and anticholinesterase agents are, in fact, the same pharmacological group of substances. There are several types of these drugs, which differ in chemical structure and reversibility of action. Cholinesterase blockers are divided into reversible and irreversible.
Means of reversible action
Anticholinesterase agents are drugs of reversible action, they are chemically esters of carbamic acid and various amino alcohols. The acid ending becomes a component of the reaction that blocks cholinesterase, which establishes a much more stable bond with the enzyme molecule than that formed when interacting with acetylcholine itself. The complete destruction of this compound occurs by hydrolysis within 3-4 hours.
Reversible anticholinesterase agents include Galantamine, Physostigmine, Prozerin (or Neostigmine), Pyridostigmine, Oksazil, Rivastigmine, Edrophonium.
Organophosphorus - substances of irreversible action
Irreversible drugs of this group are organophosphorus compounds. Thesesubstances block acetylcholinesterase for a long time. Phosphorus, which is part of their molecules, forms a stable compound with the enzyme, which can exist in the body for several days and even weeks. Restoration of the required amount of acetylcholinesterase occurs through the formation of new molecules. This group of compounds includes "Phosfakol", "Armin", "Chlorophos", "Karbofos", "Dichlorvos", poisonous substances used during military operations - sarin and soman.
Organophosphate preparations are highly toxic. They are often used in everyday life as insecticides; poisoning is possible if they are used incorrectly and safety measures are not followed.
Effects of anticholinesterase drugs
With a certain similarity of the effects that anticholinesterase drugs produce on the body, the indications for prescribing each of them will be special. You can consider the practical effect when introduced into the body using the example of "Prozerin".
"Prozerin" is available in ampoules as a 0.05% solution and is administered subcutaneously or intravenously. When released into the blood, it facilitates the passage of impulses in the neuromuscular transmission and ganglia of the autonomic nervous system. In the patient's condition, this manifests itself as follows:
- due to the contraction of the circular muscle of the iris, the pupil narrows;
- accommodation spasm occurs, the lens takes on a more convex shape due torelaxation of the zinn ligament, the focus of vision is set to the near distance, the ability to distinguish distant objects is sharply reduced;
- heart rate drops;
- the tone of the smooth muscles of the internal organs increases - the respiratory tract, stomach and intestines, uterus, bladder;
- strengthening skeletal muscle contractions due to improved transmission of impulses in synapses;
- increased secretion of exocrine glands - sweat, salivary, bronchial, gastric.
Application
The listed effects determine the use of this group of drugs in medicine in various cases. Indications for the use of anticholinesterase agents are not limited to specific diseases, as they have an effect on the central and peripheral nervous system, which causes a general effect on the entire body. Most often they are prescribed for violations of the innervation and tone of the skeletal or smooth muscles.
Consider the possibilities of treatment with anticholinesterase agents using the example of "Prozerin". This reversible drug is used for myasthenia gravis, an autoimmune disease that is expressed in the weakness of skeletal muscles. This disease is manifested first by a decrease in the tone of the mimic muscles, then by a weakening of the muscles of the neck, upper and lower extremities; in severe cases, there is a violation of breathing due to insufficient work of the diaphragm. "Prozerin" has a symptomatic effect on the body, restoringtransmission of impulses in neuromuscular transmissions, thereby increasing muscle tone and facilitating motor activity.
Also, this drug is prescribed in the postoperative period with atony of the gastrointestinal tract or bladder. In ophthalmology, it is occasionally prescribed for glaucoma to reduce intraocular pressure. As an antagonist, it is used in overdose of muscle relaxants and antidepolarizing drugs. Occasionally, "Prozerin" is used to stimulate muscle contractions with weak labor activity.
Alzheimer's disease
Reversible drugs have found application in the treatment of diseases of the central nervous system, difficult to treat. In Alzheimer's disease, "Galantamine" is prescribed - an alkaloid obtained from snowdrop tubers of the genus Galantus ("Rivastigmin", aka "Exelon"), but Donepezil has become the most therapeutically effective, which selectively blocks acetylcholinesterase in the synapses of the brain and practically does not affect it on the periphery of the nervous system.
Contraindications
Based on the effects of reversible anticholinesterase drugs, epilepsy, bronchial asthma, angina pectoris, Parkinson's disease and various disorders of the conduction system of the heart are contraindications to their use.
Symptoms of overdose and AChE poisoning
Poisoning with anticholinesterase drugs gives symptoms directly related to excessive stimulation of receptors sensitive toacetylcholine. There is a narrowing of the pupils, a slowdown in the heart rate (bradycardia), bronchospasm and - as a result - symptoms of suffocation, increased gastrointestinal peristalsis up to vomiting and diarrhea, frequent urination. Arterial pressure gradually decreases as a result of the inhibitory effect of the vagal nerve. There are chaotic contractions and twitches of the skeletal muscles and tongue due to impaired conduction in neuromuscular transmissions.
FOS poisoning
Ingestion of organophosphorus compounds causes a clinical picture similar to poisoning with reversible anticholinesterase drugs. Symptoms may be more pronounced due to higher drug toxicity. To the symptoms of poisoning at the somatic level, effects are added at the level of the central nervous system - confusion, disorientation, respiratory depression.
Organophosphorus compounds cause severe miosis, blurred vision, suffocation, sweating, severe vomiting, psychomotor agitation - the patient begins to panic, he becomes uncontrollable. Due to spasms of smooth muscles, there is a sharp pain in the abdomen. When the condition worsens, convulsions occur, blood pressure drops, and coma develops. Death can occur due to paralysis of the respiratory center.
Similar symptoms are observed in case of fly agaric poisoning. This is due to the content of muscarine in them, a poison with a cholinomimetic effect.
Poisoning action
Medicalhelp in case of poisoning with anticholinesterase agents can only be provided by a specialist. In these cases, a solution of "Atropine" is injected subcutaneously, the appointment of "Metacin" or other anticholinergics is possible. It is necessary to maintain breathing at the proper level. Tracheotomy, mechanical ventilation and oxygenation may be used.
In case of household poisoning with FOS, the source of the poison entering the body is determined. If the substance has penetrated the skin, it is washed off with a 3-5% soda solution or soap and water. In the case when the drug was taken orally, gastric lavage is performed, multiple enemas are given, adsorbents or laxatives are given. If the organophosphorus compound has already managed to get into the blood to a greater extent, forced diuresis is prescribed with the help of diuretics. In some cases, they resort to blood filtration methods using hemodialysis and hemosorption.
Additionally, in case of FOS poisoning, cholinesterase reactivators are prescribed, which, when administered in the first hours after intoxication, are able to restore blocked enzymes. It can be "Isonitrozin", "Trimedoxime", "Dipiroxime". If blood pressure is elevated, antihypertensive drugs are symptomatically prescribed. Preference should be given to those that do not affect the central nervous system. With a weakening of spontaneous breathing, artificial ventilation of the lungs and oxygen supply are indicated.
