Poisoning with anticholinesterase agents. What is anticholinesterase drugs?
The transfer of impulses to neurons is provided by special substances - mediators. One of the neurotransmitters is acetylcholine. These substances, being in synapses, affect the cell membranes, causing their inhibition or excitation and causing various effects. Excess neurotransmitters are cleaved by special enzymes.
Anticholinesterase drugs: properties and uses of
Anticholinesterase drugs include those that inhibit the cholinesterase enzyme. This enzyme cleaves the neurotransmitter acetylcholine by hydrolysis, which ensures the transfer of impulses in sensitive synapses of parasympathetic nerves, ganglia and in all somatic fibers. To situationally enhance the action of acetylcholine on neurons and stimulate certain parts of the nervous system, anticholinesterase agents have been developed. The use of these drugs has an effect on the entire body as a whole.
The action of anticholinesterase agents is similar to the effect of cholinergic nerve stimulation. These drugs interact with the same site of activity of the surface of the receptor as acetylcholine, thereby creating a potential action of the nerve endings. Cholinomimetics and anticholinesterase drugs are, in fact, the same pharmacological group of substances. There are several types of these drugs that differ in chemical structure and reversibility of action. Cholinesterase blockers are divided into reversible and irreversible.
Means of reversible action
Anticholinesterase agents - preparations of reversible action, are by chemical structure by esters of carbamic acid and various amino alcohols. The component of the reaction that blocks cholinesterase becomes the acidic end, 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 for 3-4 hours.
Anticholinesterase agents of reversible effect include Galantamine, Physostigmine, Prozerin( or Neostigmine), Pyridostigmine, Oxazil, Rivastigmine, Edrophony.
Organophosphate - irreversible substances
Non-reversible drugs of this group are organophosphorus compounds. These substances 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. Recovery of the required amount of acetylcholinesterase occurs by the formation of new molecules. This group of compounds includes "Fosfakol", "Armin", "Chlorophos", "Carbophos", "Dichlorvos", poisonous substances used in the course of military operations - sarin and soman.
Organophosphate drugs are highly toxic. They are often used in everyday life as insecticides;Poisoning is possible if they are used incorrectly and if safety measures are not taken.
Effects of anticholinesterase drugs
With a certain similarity in the effects that anticholinesterase drugs produce on the body, the indications for each of them will be special. Consider the practical action when introduced into the body can be an example of "Proserin."
Prozerin is available in ampoules as a 0.05% solution and is administered subcutaneously or intravenously. When ingested, it facilitates the passage of impulses in neuromuscular transmissions and ganglia of the autonomic nervous system. In the patient's condition, this manifests itself as follows:
- because of the contraction of the circular muscle of the iris, the pupil narrows;
- there is a spasm of accommodation, the lens assumes a more convex shape due to relaxation of the zinn ligament, the focus of vision is set to a short distance, the ability to distinguish far-away objects sharply decreases;
- decreases the heart rate;
- increases the tone of smooth muscles of internal organs - respiratory tract, stomach and intestines, uterus, bladder;
- enhances contractions of skeletal muscles due to improved passage of pulses in the synapses;
- secretion of exocrine glands increases - sweat, salivary, bronchial, gastric.
The above effects cause the use of this group of drugs in medicine in various cases. Indications for the use of anticholinesterase drugs are not limited to specific diseases, since 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 innervation and tone of skeletal or smooth muscles.
It is possible to consider the possibilities of treatment with anticholinesterase agents using the example of "Proserin".This drug of reversible action is used for myasthenia gravis, an autoimmune disease that is expressed in the weakness of skeletal muscles. This disease manifests itself first by a decrease in the tone of mimic muscles, then by weakening 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."Proserin" acts symptomatically on the body, restoring the transmission 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, he is occasionally prescribed for glaucoma to reduce intraocular pressure. As an antagonist used in overdose of muscle relaxants and antidepolarizing agents. Occasionally, "Proserin" is used to stimulate muscle contractions with weak labor.
Drugs of reversible action have found application in the disease of the central nervous system, which is difficult to treat. In Alzheimer's disease, "Galantamine" is prescribed - an alkaloid obtained from tubers of snowdrops of the genus Galantus( "Rivastigmine", also "Exelon"), but the most therapeutically effective was "Donepezil", which selectively blocks acetylcholinesterase in the synapses of the brain and practically does not affect iton the periphery of the nervous system.
Based on the effects of anticholinesterase drugs of reversible action, contraindications to their use are epilepsy, bronchial asthma, angina pectoris, Parkinson's disease and all kinds of disorders of the conduction system of the heart.
Symptoms of an overdose and poisoning of AChE
Anticholinesterase poisoning gives symptoms directly associated with excessive stimulation of receptors sensitive to acetylcholine. There is a narrowing of the pupils, a slowing of the heart rate( bradycardia), a spasm of the bronchi and, as a result, symptoms of suffocation, increased peristalsis of the gastrointestinal tract until vomiting and diarrhea, frequent urination. Gradually decreases blood pressure as a consequence of the inhibitory effect of the vagus nerve. There are chaotic contractions and twitching of skeletal muscles and tongue due to impaired conduction in neuromuscular transmissions.
The ingestion of organophosphorus compounds causes a clinical picture similar to that of anticholinesterase agents of reversible action. Symptoms may appear brighter due to higher toxicity of the drugs. To the symptoms of poisoning at the somatic level, effects are added at the level of the central nervous system - confusion, disorientation, respiratory depression.
Organophosphate compounds cause sharp miosis, visual impairment, suffocation, sweating, severe vomiting, psychomotor agitation - the patient begins to panic, he becomes uncontrollable. Because of spasms of smooth muscles, a sharp pain in the abdomen is felt. If the condition worsens, convulsions occur, blood pressure drops, coma develops. Death can occur as a result of paralysis of the respiratory center.
Similar symptomatology is observed when poisoning with fly agarics. This is due to the content in them of muscarin - a poison with holinomimeticheskim action.
Actions for poisoning
Medical treatment for poisoning with anticholinesterase agents may be provided only by a specialist. In these cases, a solution of "Atropine" is injected subcutaneously, possibly the appointment of "Metazina" or other anticholinergic blockers. It is necessary to maintain breathing at the proper level. Tracheotomy, artificial ventilation and oxygenation may be used.
When household poisoning FOS determine the source of poison into the body. If the substance has penetrated through the skin, it is rinsed with 3-5% soda solution or water and soap. In the case where the drug was ingested, gastric lavage, multiple enemas, adsorbents or laxatives are performed. If the organophosphorus compound has already managed to get more into the blood, an intensive diuresis is prescribed with the help of diuretics. In some cases, resort to methods of blood filtration with hemodialysis and hemosorption.
Additionally, in the poisoning of OPC, cholinesterase reac- tors are prescribed, which, when introduced in the first hours after intoxication, can restore blocked enzymes. It can be "Izonitrozin", "Trimedoksim", "Dipiroksim".If the arterial pressure is raised, hypotensive drugs are symptomatically prescribed. Preference should be given to those that do not affect the central nervous system. With the weakening of independent breathing, artificial ventilation of the lungs and oxygen supply are shown.