M Holinomimetics Basic effects. Holinomimetic means. Lowering intraocular pressure
M-cholinomimetics have a direct stimulating effect on M-Hololine trampulators. The benchmark of such substances is the alkaloid muscarine, which has the electoral influence against M-cholinoreceptors. Muskarine is not a medicine, but the poison contained in the moon can be the cause of sharp poisoning.
Muscarin poisoning gives the same clinical picture and pharmacological effects, like AHE means. The difference is one thing - here is a direct action on M-receptors. The same main symptoms are noted: diarrhea, difficulty breathing, abdominal pain, savory, narrowing of the pupil (MIOS - the pupil muscle is reduced), the intraocular pressure decreases, the accommodation spasm is noted (near point of vision), confusion, convulsion, coma. Localization of M-receptors: M1-mucousness of the stomach; m2 heart; M3-glands
M-Holinomimetics in medical practice are most widely used: 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 pylocarpine), aceclidine (ACECLIDINUM) - AMP.- 1 and 2 ml 0.2 % r-ra; 3% and 5% - eye ointment.
Pilocarpine is an alkaloid from the Pilocarpus Microphyllus shrub, (South America). Currently obtained synthetically. It has a direct M-cholinomimetic effect.
Stimulating effector organs receiving cholinergic innervation, M-cholinomimetics cause effects similar to those observed in irritation of vegetative quinerity nerves. Especially greatly raises the pilocarpine secretion of glands. But the pylocarpine, being a very strong and toxic drug, is applied only in eye practice when glauer. In addition, pylocarpines are used during retinal vessels. Used locally in the form eye drops (1-2% r-p) and eye ointment (1 and 2%) and in the form of eye films. He narrows the pupil (from 3 to 24 hours) and reduces intraocular pressure. In addition, the accommodation spasm causes. The main difference from AHE funds is that the pylocarpine has a direct effect on M-cholinproptestructors of the eye muscles, and the AHE is mediated. Replaced in tablets (5 Mg), in dentistry (xerophthalmia).
Aceclidine (ACeclidinum) -nut from production - synthetic M-cholinomimetics of direct action. Less toxic. Apply for local and resorbative action, i.e., used both in eye practice and with general impact. Aceclidine is prescribed at glaucoma (a little annoying in a conjunct), as well as at Atony's CCT (in the postoperative period), bladder and uterus. In parenteral administration, there may be side effects: diarrhea, sweating, salivament. Contraindications: bronchial asthma, pregnancy, atherosclerosis.
Cisapride-modern prokinic
Means blocking M-cholinoreceptors (M-cholinoblastors, Atropine-like)
M-cholinoblockers or M-cholinolics, preparations of the Atropine group are funds blocking M-cholinoreceptors.
The typical and most well-studied representative of this group is atropine - hence and the group is called atropine-like funds. M-cholinoblocators block peripheral M-cholinoreceptors, located on the effector cell membrane at the end of postganglyonary cholinergic fibers, i.e., block parasympathetic, cholinergic innervation. Blocking predominantly the muscarine effects of acetylcholine, the effect of atropine on vegetative ganglia and non-muscular synapses does not apply. Most atropine-like funds block M-cholinoreceptors in the central nervous system. A m-cholinoblocator with a high selective action is atropine (ATROPINI Sulfas; Tablets 0.0005; Ampules 0.1% - 1 ml; 1% eye ointment).
Atropine is an alkaloid contained in the plants of the Polenic family. Atropine and alkaloids close to him are contained in a number of plants:
Handicraft (Atropa Belladonna);
Belene (Hyoscyamus Niger);
Datura Stramonium.
Atropine is currently obtained synthetically, i.e., by chemical. The name Atropa Belladonna is paradoxically, since the term "Atropos" means "three fates leading to the inglorious ending of life", and "Belladonna" - "charming woman" (Donna - woman, Bella - women's name in Romanesque languages). This term is due to the fact that the extract from this plant, corpusing the beauties of the Venetian courtyard in the eyes, gave them a "radiance" - expanded pupils. The mechanism of action of atropine and other means of this group is that, blocking M-cholinoreceptors, competing with acetylcholine, they interfere with the interaction with them of the mediator. The synthesis, liberation and hydrolysis of acetylcholine do not act. Acetylcholine stands out, but does not interact with receptors, since atropine has greater affinity (affinity) to the receptor. Atropine, as well as all M-cholinoblocators, reduces or eliminates the effects of irritation of cholinergic (parasympathetic) nerves and the effects of substances with M-cholinomimetic activity (acetylcholine and its analogues, AHE funds, M-cholinomimetics). In particular, atropine reduces the effects of irritation N. Vagus. Antagonism between acetylcholine and atropine is competitive, therefore, with an increase in acetylcholine concentration, the action of atropine at the point of the Muscarin application is eliminated.
The main pharmacological effects of Atropine
Safety spasmodic properties are especially expressed in atropine. Blocking M-cholinoreceptors, atropine eliminates stimulating effect parasympathetic nerves for smooth muscle bodies. The tone of the muscles of the gastroof, biliary ducts and the gallbladder, bronchi, ureters, bladder is reduced.
Atropine affects the tone of the eye muscles. We will analyze the effects of the effect of atropine on the eyes:
with the introduction of atropine, especially with its local application, due to the M-cholinoreceptor block of the circular muscle of the iris, there is an expansion of the pupil - mydriasis. Midships are also intensified as a result of saving sympathetic innervation M.Dilatator Pupillae. Therefore, atropine on the eyes in this regard is valid for a long time - up to 7 days;
under the influence of atropine loses the tone of the ciliary muscle, it is complied, which is accompanied by the tension of the zinnoy ligament supporting the lens. As a result, the lens is also compacted, and the focal length of such a lens is extended. The lens establishes the vision to the far point of the vision, so the nearby sick items are not clearly perceived. Since the sphincter is in a paralysis state, it is not capable of narrowing the pupil when viewing nearby objects and photophobia (light-free) occurs during bright light. This state received the name of the paralysis of accommodation or cycliplegia. Thus, atropine is also a midwarter and cyclopelic. Local use of 1% of the atropine solution causes the maximum mydritic effect for 30-40 minutes, and the full restoration of the function occurs on average after 3-4 days (sometimes up to 7-10 days). Accommodation paralysis occurs after 1-3 hours and lasts up to 8-12 days (approximately 7 days);
relaxation of the ciliary muscle and shifting the lens into the front chamber of the eye is accompanied by a disturbance of outflow intraocular fluid From the front chamber. In this regard, atropine or does not change intraocular pressure In healthy individuals, or in people with a shallow front chamber and in patients with a narrow-angled glaucoma, it may even increase, i.e., lead to the exacerbation of the attack of glaucoma.
Indications for the use of atropine in ophthalmology
In ophthalmology, atropine is used as a midriad in order to cause cycloplegia (accommodation paralysis). Midships are needed in the study of the fundus and in the treatment of patients with irita, iridocyclitis and keratitis. In the latter case, atropine is used as a means of immobilization, contributing to the functional entry of the eye.
To determine the true refractive capacity of the lens when selecting points.
Atropine is a means of choice if it is necessary to obtain the maximum cycloplegia (accommodation paralysis), for example, when correction of accommodation squint.
The effect of atropine on the organs with a smooth muscles. Atropine reduces the tone and motor activity (peristaltics) of all gastrointestinal departments. Atropine also reduces the peristaltics of the ureters and the bottom of the bladder. In addition, Atropine relaxes the smooth muscles of bronchi and bronchiol. With respect to biliary tract, the antopine antopine is weak. It should be emphasized that the anthropine spasmodic effect is especially pronounced against the background of the previous spasm. Thus, the atropine has an antispasmodic effect, i.e., atropine acts in this case as a spasmolitic. And only in this sense, atropine can act as a "anesthetic" means.
The effect of atropine on the gland of the exterior secretion. Atropine sharply weakens the secretion of all the glands of the external secretion, with the exception of dairy. At the same time, the atropine blocks the secretion of liquid water-resistant saliva, caused by the stimulation of the parasympathetic department of the autonomic nervous system, dryness in the mouth occurs. Decreases tear. Atropine reduces the volume and overall acidity of gastric juice. At the same time, the depression, the weakening of the secretion of the specified glands can be up to their complete shutdown. Atropine reduces the secretory function of the glands in the cavities of the nose, mouth, pharynx and bronchi. The secret of the bronchial glands becomes viscous. Atropine even in small doses inhibits the secretion of sweat glands.
The effect of atropine on the cardiovascular system. Atropine, withdrawing a heart from under control N.Vagus, causes tachycardia, i.e. increases the frequency of heart abbreviations. In addition, atropine contributes to the relief of the pulse in the conductive heart system, in particular in the AV node and at the atrocadic bunch as a whole. These effects are less pronounced in the elderly, since in the therapeutic doses, atropine does not have a significant effect on the peripheral blood vessels, they are reduced by N.Vagus tone. At the blood vessels in therapeutic doses, atropine does not have a significant action.
The effect of atropine on the central nervous system. In the therapeutic doses, atropine does not affect the CNS. In the toxic doses, atropine sharply excites the neurons of the cerebral cortex, causing motor and speech arousal, reaching mania, delirium and hallucinations. The so-called, "Atropin psychosis" arises, leading further to a decrease in functions and the development of coma. It is also characterized by stimulating influence on the respiratory center, but when the dose is raised, breathing may occur.
Indications for the use of atropine (except ophthalmic)
As an ambulance with:
intestinal
renal
hepatic colic.
In bronchial spasms (cm.adrenomimetics).
IN complex therapy patients with ulcerative ulcer of the stomach and 12-rosewind (reduces the tone and secretion of glands). Used only in the complex of therapeutic measures, as secretion reduces only in large doses.
As a means of premium in anesthesiological practice, atropine is used widely before operation. As a means of drug preparation of a patient for surgery atropine use because it has the ability to suppress the secretion of salivary, nasopharynk and tracheobronchial glands. As is known, many drugs for anesthesia (ether in particular) are strong jums of mucous membranes. In addition, blocking m-cholinoreceptors of the heart (the so-called vagolitical action), Atropine warns negative reflexes on the heart, including the possibility of its reflex stop. Using atropine and reducing the secretion of these glands, prevent the development of inflammatory postoperative complications in the lungs. From here it is clear the meaning of the fact that the renexcatalogists attach, when they talk about the full possibility of "breatind" the patient.
Atropine is used in cardiology. The M-choline-blocking effect of it on the heart is favorable with some forms of heart arrhythmias (for example, an atrioventricular block of vagus origin, i.e., in bradycardians and heart blocks).
Widespread applications found atropine as ambulance means for poisoning:
but) AHE fundsmi (FOS)
b) M-cholinomimetics (muscarin).
Along with Atropine, other atropine-like drugs are well known. Natural atropine-like alkaloids include scopolamine (hyoscin) Scopolominum Hydrobromidum. Available in ampoules 1 ml - 0.05%, as well as in the form of eye drops (0.25%). It is contained in the Mandragore plant (Scopolia Carniolica) and in the same plants in which there is an atropine (handsome, whlen, donber). Structurally close to Atropine. It has pronounced M-choline-blocking properties. An essential difference from atropine one thing: in therapeutic doses, the scopolamine causes slight calmness, depression of the central nervous system, sweating and sleep. It acts oppressingly on the extrapyramidal system and the transmission of excitation from the pyramids on the brain motorway. The introduction of the drug in the cavity of the conjunct is less prolonged mydriasis. Therefore, the anesthesiologists use scopolamine (0.3-0.6 mg P / K) as a means of premedication, but usually in combination with morphine (only not in old people, as it can give a confusion). It is sometimes used in psychiatric practice as a soothing, and in neurology - for the correction of Parkinsonism. Skopolamine is shorter than Atropine. Also used as an antiemetic and soothing agent for sea and air diseases (Tablets "Aeron" are a combination of scopolamine and hyoscyiamine). The group of alkaloids obtained from vegetable raw materials (diabstore) is also placifillain. (Platyphyllini HydrotartRas: Tablets of 0.005, as well as ampoules 1 ml - 0.2%; Eye drops - 1-2% solution). It acts about also, causing similar pharmacological effects, but asleeping atropine. It has a moderate gangli-blocking effect, as well as a direct myotropic antispasmodic effect (papaverinoid), as well as on vascular centers. It has a soothing effect on the CNS. Apply Platifillin as an antispasmodic during the spasms of the gastrointestinal tract, bile ducts, gallbladder, ureters, with an increased tone of brain and coronary vessels, as well as to relieve bronchial asthma. In the eye practice, the drug is used to expand the pupil (actual atropine acts in short, does not affect accommodation). We are injected under the skin, but it should be remembered that the solutions of 0.2% concentration (pH \u003d 3.6) are painful.
For eye practice, homatropinum is proposed (Homatropinum: 5 ml bottles - 0.25%). It causes an expansion of the pupil and accommodation paralysis, i.e. it acts as a midriad and cyclopelic. Ophthalmological effects caused by homatropine last 15-24 hours, which is much more convenient for the patient compared with the situation when atropine is used. Risk of lifting of the WGD less, because Weaker atropine, but at the same time, the drug is contraindicated in glaucoma. The rest does not differ in principle from atropine, it is used only in eye practice.
The synthetic drug metacin is a very active M-cholinoblocator (methacinum: in tablets 0.002; in ampoules 0.1% - 1 ml. Quaternary, ammonium compound, which penetrates badly through the BGB. This means that all its effects are due to peripheral M-choline-lock Action. From atropine is characterized by a more pronounced broncholy action, the lack of influence on the CNS. Higher than atropine, suppresses the secretion of salivary and bronchial glands. Used when bronchial asthma, peptic ulcer, for relieving renal and liver colic, for premium in anesthesiology (in / in 5-10 min., in / m - for 30 minutes) - more convenient atropine. Over the painful effect exceeds atropine, it causes tachycardia less.
IPRATRUPIUM Bromide-forbing bronchospasm, produced in aerosol
Antichern drugs containing atropine also use drugs (belladonna), for example, masting extracts (thick and dry), belladonny tinctures, combined tablets. These weak drugs and ambulance are not used. Applied at home at the prehospital stage.
Finally, a few words about the first representative of the electoral antagonists of muscarinic receptors. It turned out that in various organs of the body there are various subclasses of muscarinic receptors (M-one and M-two). Recently, the preparation of gastrocepin (Pyrenspine) was synthesized, which is a specific inhibitor of M-one-cholinoreceptors of the stomach. It is clinically manifested by intense intensifying the secretion of gastric juice. Thanks to the pronounced oppression of the secretion of the gastric juice, the gastrocepin causes persistent and fast pain relief. Used under the ulcer of the stomach and 12-rosewood, gastritis, dudenites. It has a significantly less than the number of side effects and practically does not act on the heart in the CNS does not penetrate.
Side effects of atropine and its drugs. In most cases, side effects are a consequence of the latitude of the pharmacological effects studied drugs and manifest themselves dryness in the mouth, the difficulty of swallowing, the intestinal aton (constipation), the fuzziness of visual perceptions, tachycardia. Local use of atropine can cause allergic reactions (dermatitis, conjunctivitis, edema). Atropine is contraindicated in glaucoma.
Acute poisoning by atropine, atropine-like drugs and plants containing atropine. Atropine is not a harmless agent. It is enough to say that even 5-10 drops can be toxic. The fatal dose for adults when taking orally from 100 mg, for children - with 2 mg; With parenteral administration, the drug is even more toxic. The clinical picture in the poisoning of atropine and atropine-like preparations is very characteristic. The symptoms associated with the suppression of the cholinergic effects and the effects of the poison on the CNS are noted. At the same time, depending on the dose of the drug, they allocate a light and serious flow.
With light poisoning, the following clinical signs are developing:
expansion of pupils (MIDRIAZ), PhotoFobia;
dry skin and mucous covers. However, due to the reduction in the sweating of the skin hot, red, there is an increase in body temperature, sharp hyperemia of the face (the face "silent with heat");
dryness mucous
strongest tachycardia;
athion intestines.
In severe poisoning, against the background of all these symptoms, psychomotor excitation performs to the fore, i.e., excitation and mental, and motor. Hence the famous expression: "whites are launched." Motor coordination is disturbed, the speech is blurred, the consciousness is confused, hallucinations are noted. The phenomena of atropine psychosis are developing, requiring psychiatrist intervention. Subsequently, the depression of a vasodent center with a sharp expansion of capillaries may occur. Collapse, coma and palsy of breathing developing.
Assistance MEASURES Atropin
If the poison is accepted inside, it is an attempt to pour it if possible faster (stomaching, laxatives, etc.); Binding - tannin adsorbing - activated carbon, forced diuresis, hemosorption. It is important to apply specific treatment here.
Before washing, a small dose (0.3-0.4 ml) of diazepam (sybazone, relaignum) should be introduced to combat psychosis, psychomotor excitation. The dose of Sibazone should not be big, since the patient can develop paralysis of vitality centers. In this situation, it is impossible to introduce aminazine, as it has its own muscarin-like influence.
It is necessary to displace the atropine due to the cholinoreceptors, various cholinomimetics use for these purposes. It is best to use Fizostigmin (V / B, slow, 1-4 mg), which is made abroad. We use AHE products, most often prozerne (2-5 mg, p / k). Drugs are introduced with an interval of 1-2 hours until there are signs of eliminating the blockade of muscarinic receptors. The use of physostigmine is preferable because it penetrates well through the BCU in the CNS, reducing the central mechanisms of atropine psychosis. To facilitate the state of photophobia, the patient is placed in a darkened room, make rubbing with cool water. Careful care is needed. Frequently required artificial respiration.
N-cholinergic
Let me remind you that n-cholinoreceptors are localized in vegetative ganglia and end plates of skeletal muscles. In addition, n-cholinoreceptors are in carotid glomers (they are necessary to respond changes in blood chemical), as well as the brain layer of the adrenal glands and the brain. The sensitivity of n-cholinoreceptors of different localization to chemical compounds of non-etinakov, which makes it possible to obtain substances with predominantly influence on vegetative ganglia, cholinoreceptors of neuromuscular synapses, CNS.
Means stimulating n-cholinoreceptors are called n-cholinomimetics (nicotinomimetics), and blocking - n-cholinoblocators (nicotinal blockers).
It is important to emphasize the following feature: all H-cholinomimetics are excited by n-cholinoreceptors only in the first phase of their action, and in the second phase, the excitation is replaced by the oppressive effect. In other words, n-cholinomimetics, in particular the Nicotine reference substance, possess a two-phase effect on n-cholinoreceptors: in the first phase, nicotine acts as a Holinomimetic, in the second - as a H-cholinoblocator.
Subject: "Holinomimetics »
Plan:
1) The concept of M-and N-cholinoreceptors.
2) Classification of cholinomimetics.
3) Localization of M-cholinoreceptors.
4) Comparative characteristics of M-cholinomimetics.
5) Muscarin poisoning symptoms. First aid.
6) Localization of n-cholinoreceptors.
7) Comparative characteristics of n-cholinomimetics.
8) comparative characteristics of m, n-cholineimetics direct and indirect action(Anticholinesterase agents).
9) FOS poisoning symptoms. First aid.
All cholinoreceptors are divided:
1.M-cholinoreceptors-Momscarino-sensitive. Musarine-poison of the Mumor.
2.N-cholinoreceptors-nico-sensitive. Nicotine-alkaloid leaves of tobacco.
When studies of the nervous system on animals were conducted, it was found that the receptors localized in some organs are equally sensitive and react to small doses of Muskarin, bind to it, while causing the change in the functions of these organs and do not respond at all to nicotine. They were called m-cholinoreceptors. Receptors in other organs are sensitive to small nicotine doses, are associated with it and cause changes in the functions of these organs, and do not react to muscarine. They were called n-cholinoreceptors. All cholinoreceptors are divided into subtypes: M1, M2, HN, N M. Each subtype has its own strict localization and a specific function. Drugs acting in cholinergic systems are divided into 2 groups: cholinomimetics and cholinoblocators.
Classification of cholinomimetics
M-Holinomimetics: N-cholinomimetics:
Pylocarpine, aceclidine, cisapride. Cytion, Lobelin,
Anabazin, "Tablex," Lobesil "
M, n-cholinomimetics:
Direct Action: Indirect Action
Acetylcholine Anticholinesterase
Karbicholin.
Indirect action (anticholinesterase):
a) reversible action: b) irreversible action:
Fizostigmin Armin.
Galanamin FOS (phosphorganicorganic
Prezero (Neostigmin) Connections): Chlorofos,
Oxazil (Ambenonium) Dichlofos
Pyridostigmine (Calimin) Tabun, Zarin
Distigmin (ulitid) (chemical attack funds)
M-cholinomimeticsa direct exciting effect on m-cholinoreceptors are rendered. A typical representative is muscarine (mushroom alkaloid mushroom).
Localization of M-cholinoreceptors:
M-cholinoreceptorslocalize mainly in PS nervous system:
1). In CNS (subcortical structures, reticular formation, bark);
2) in postganglyonary fibers in the heart. They contain a wandering nerve, it has a braking effect on the heart;
3) in postganglyonar P.S. Fibers innervating smooth muscles: bronchi, J.K.T., eye, urinary and biliary tract;
4) in postganglyonar P.S. fibers, innervating cells of glands (salivary, stomach, bronchial);
5) in postganglyonar S.. Fibersinnervating skin.
Effects that occur in organs when excitation
M-cholinoreceptors M-cholinomimetics drugs:
On the heart:
1. In / in the introduction of m-cholinomimetics cause a sudden stop of the heart-parenterally they are not used !!!
2.Bradiconde (deceleration of heart abbreviations). The brake vagus effect on the heart increases (localization in the conductive heart system);
3. Reduced A.D (hypotension);
On bronchi:
1. Make the bronchi, to bronchospasm (attack of choking), especially in patients with bronchial asthma. (not desirable effects)
2. The use of the secretion of bronchial glands.
Positive effects that have practical interest:
1. Removal of intestinal motility and urinary tract: The tone and intestinal peristalistic increases, the sphincters relax at the same time, while the speed of moving the dietary mass, gases increases - the intestinal atony is eliminated, the meteorism, constipation (defecation delay) occurs during overdose.
2. The extension of the tone of the bladder - the imony of the bladder is eliminated, urination delay occurs during overdose.
3. Improving the tone of eye muscles: a) the circular muscle of the iris is reduced, as a result of which the pupil is narrowed (myiosis); b) As a result of the reduction in the eyelic muscles of the eye, the outflow of the fluid from the front chamber of the eye through the fantasies of space (the brabecuber network is at the base of the iris) and the channel helmets into the venous system of the eye, which leads to a decrease in intraocular pressure - is used to treat glaucoma; c) Reducing the circular muscles of the eye (ciliary body of the eye) leads to the movement of the abdomen of the muscles, to which Zinnov bundle is attached closer to the lens. As a result, the bundle is relaxed - the lens capsule ceases to stretch and crystal becomes more convex (since it is very elastic). As a result, it appears accommodation spasm (Eye is installed on a close vision) - the objects are poorly visible.
Glaucoma isthe disease with a resistant increase in intraocular pressure and sawing pain in the eye leading to blindness. Its aggravation (glaucoma crisis) requires emergency! Eye drops are used to treat glaucoma: Pilocarpine, aceclidinewhich act several hours: the heedy canal presses with a finger so that the solution does not glasses in the nasal cavity - bury in the conjunction bag.
When overdosing m-cholinomimetics The effects caused by them are clear, as well as when poisoning by amanomor or drugs of this group, the so-called holieregic effects(They may be partly to cause drugs of different pharmacological groups):
Bradycardia, decline of A.D (hypotension);
Difficulty breathing (bronchospasm);
Reinforced sweating, salivation, abundant sputum;
Reinforced, painful intestinal peristalsis, which is accompanied by vomiting, diarrhea;
The tone of the bladder increases, which leads to a delay in urination;
Expansion of skin vessels;
Narrowing of the pupil-spasm of accommodation;
Far items are not clearly visible;
Psychomotor arousal and convulsions.
Death may occur from the paralysis of the respiratory center.
All symptoms are easily removed by M-cholinoblocators, which cause opposite effects, because They are one-sided antagonists, for example, a solution of atropine sulfate, administered n / k.
Indications:
Treatment of glaucoma, prescribe eye drops, films, ointment with pilocarpine. In connection with its high toxicity, it is impossible to introduce parenterally.
Under the atony of the stomach, intestines and bladder after operating or pathological and most often, aceclidine is used in the solution, they are injected subcutaneously. It is less toxic than pylocarpine.
Contraindications: B.ronchial asthma, heart disease - heart attacks, vices, pregnancy, epilepsy, hyperkinosis-elevated tone of smooth muscles of internal organs.
Pilocarpin- Alkaloid, obtained from the Brazilian Plant Pilocarpus Pinnatifolius Jaborandi. Inside (PER OS) are not prescribed, with in / in the introduction causes a heart stop !!! Apply only locally, in ophthalmology: 1.) In the form of eye drops of 1% aqueous solution of 1.5 ml. In a tube - dropper and 1%, 2% solutions of 5 and 10 ml. In the vials, prescribe 1-2 cap., 3-4 p. per day in a conjunction bag to reduce intraocular pressure during glaucoma; for removing mydriasis (expansion of the pupil) after applying atropine (for the eye bottom studies); In comprehensive therapy with drops "Timol", "Proksodolol" - to reduce intraocular pressure; as part of combined drugs "Fotil", "Fotil-Forte" (pilocarpine + Timolol) ; 1% solution of 5.10 ml with methylcellulose (extended); 2) in the form of eye films of prolonged action, they are laid by the eye tweezers for the lower eyelid 1-2 times a day, collagen, swelling (wetted by tears fluid), green. Contain 2.7 mg of pylocarpine each film. Packed in Penals of 20 pieces; Eye films "Piloren" (pilocarpine 2.5 mg + adrenaline 1 mg) in 1 film; 3) Eye ointment 1%, 2%, lay the blade for the lower eyelid 1-2 times a day.
Aceclidine "Greudin", "Glaungs"a solution of 0.2% vampuls of 1 and 2 ml., P / K is administered; Powder for cooking eye drops. Applywith the imony of the bladder, increases the daily diuresis, postoperative musculature atony Zh.K.T., in obstetrics with a decrease in the tone of the uterus, to stop the uterine bleeding in after the generic period; For radiological studies of the esophagus, stomach and 12-rosewood, a solution of p / k 15 minutes to studies are introduced; in ophthalmology, the eye drops of 2% are used to narrow the pupils and lowering intraocular pressure during glaucoma; to remove mydriasis from the eye drops of homatropine - 5% The solution, with mydriase from atropine and scopolamine -MallEeefficient.
Contraindications: Bronchial asthma, heart disease, J.K.T. bleeding, epilepsy, pregnancy.
Cisapride "Coordinix", "Perventyl"tablets at 0.005, 0.01, suspension in ampoules 1 ml. Refers to prokineal, has another mechanism of action: enhances the output of acetylcholine from the presynaptic endings, especially the intestinal plexus. Increases the tone and intestinal peristalsis and the tone of the esophageal sphincter, prevents the conversion of the contents of the stomach in the esophagus. Used with stomach, reflux-esophagitis, intestinal atonia, chronic constipation, to accelerate the peristaltics during radiological studies of the gastrointestinal studies.
Contraindications:gastrointestinal bleeding, pregnancy, lactation, impaired liver and kidney functions.
Symptoms of overdose and poisoning by M-cholinomimetics:
sluting, diarrhea, vomiting, sweating, narrowing of the pupil, lowering A.D., slowdown in the heart. Easy removed H.B. - Atropine, metacin.
N-cholinomimeticsa direct exciting effect on n-cholinoreceptors are rendered.
N-cholinoreceptors are localized In the central nervous system, carotid gloms (accumulation of blood vessels in the place of the carotid artery), vegetative ganglia s and r s nervous system.
A typical representative is nicotine - Alkaloid Tobacco leaves. Very toxic, 1-2 drops of pure nicotine kills a man. In Russia, Tobacco was brought by Peter I from Holland. When combustion of tobacco, it is inhaled with smoke, in addition to nicotine phenol, carbon monoxide .inyl acid, resin. Radioactive polonium is aimed with it and the carcinogenic effect of tobacco. Smoking causes a number of diseases cardiovascular Systems, lungs, stomach, oncological diseases. The incidence of smoking is associated with the pharmacological effects of nicotine: the excitation of n-cholinoreceptors of the central nervous system, especially in the crust of large hemispheres, the stimulation of adrenal brainstones with increased emission of adrenaline, which also excites cerebral centers, increases blood pressure, increases the feeling of improving performance attention. The excited-cholinoreceptors of vegetative ganglia leads to narrowing the vessels, and the carotid zone leads to the reflex excitation of the respiratory center and the reflex emission of the vasopressin-antidiuretic hormone of the rear line of the pituitary gland, which also narrows the vessels and delays the fluid in the body. The medical importance of n-cholinomimetics is limited, only the ability to excite chemoreceptors of vessels of carotid glomes, and in this way to reflexively stimulate the operation of the respiratory center, so on. They are analeptics of reflex action. They act strongly, but briefly 2-5 minutes with in / in the introduction, which is used in the oppression of the respiratory center in the poisoning of barbiturate morphine and its counterparts (the sensitivity of its cells to CO2 decreases), then resort to reflex stimulation. When P / C and V / M administration for the proper effect it is necessary to introduce a dose of these drugs 10-20 times large, and this leads to dangerous side effects, up to the heart stop, so only in / in small doses are administered. Indications for use:1. For the resumption of respiration in the poisoning of barbiturates, opioid analgesics, carbon monoxide, the reflex stop of breathing on operations, during drowning, injuries. Apply to / in lobelin or cytisin solutions. Cytithonan aqueous solution of the alkaloid of cytisine, from seeds of a Cytisus Laburnum distribution plant, 0.15% 1 ml. Lobelin1% 1 ml of solubaloid from the Lobelia Inflate plant. 2. To cancel smoking, use: " Tablex "," Lobesil ", "Anabazin" Tablets inside or sublingual according to the scheme, gradually reducing the dose, films with cytisin for 10 pcs., Bonqually, on the gum or on the mucous membrane; chewing gum « Hamibazin ",containing anabazine, " Nicortte "containing the therapeutic doses of nicotine, a course of 20-25 days; Tablextablets containing alkaloid citisin; Anabazintablets, films, chewing gum containing tanning plants Anabasis Aphilla; "Lobesil"tablets containing 0.002mg Lobelin alkaloid. Side effects:nausea, vomiting, weakness, increased blood pressure, irritability. Contraindications: peptic ulcer of the stomach and a 12-rosewoman, organic diseases Cardiovascular system, treatment should be carried out under the supervision of the doctor.
M, n-cholinomimetics of direct action.
Carbocholine, Acetylcholine. For use in medical practice and for manufactured synthetic Acetylcholine chloride0.1, 0.2 Powder in bottles of 5 ml. Breakdown with water for injections and introduced in / m, p / k,. As the medicine is rarely used, when taking inside, it is rapidly collapsed (hydrolyzed), with parenteral administration acts quickly, but not long, it does not penetrate the BGB, does not have a central action. It is used as a vasodilator in the spasms of peripheral vessels and the arteries of the retina, rarely at the intestine and the bladder atony and the bladder, for radiological studies of the esophagus. The / in is not injected, it can cause a sharp drop in blood pressure and stop the heart. Contraindications: Bronchial asthma, angina, atherosclerosis, epilepsy. After an overdose, it is observed: a sharp decrease in blood pressure, bradycardia, a profuse sweat, myiosis (narrowing of the pupil), an increase in intestinal peristaltics, etc. In such cases, 1 ml of p / k or in / at 0.1% of the solution is injected in such cases Atropine.
Karbicholin.powder for the manufacture of 0.5-1% eye drops Ex Tempore when glauer. Mostat- 0.01% solution, applied to narrowness of pupil when eye operations, introduced into the front chamber of the eye. B.more active and more prolonged action than acetylcholine. It does not destroy when taking inside, therefore was produced in pills and solutions for injections, which are currently excluded from the state registry. It is stronger than acetylcholine increases the tone of the bladder and intestines, with local use in the form of eye drops, it reduces the eye pressure during glaucoma.
Contraindications and side effects like acetylcholine.
M, n-cholinomimetics of indirect action or anticholinesterase agents.Inhibit the true and false cholinesterase is an enzyme that destroys acetylcholine, as a result of which the mediator accumulates in the cholinergic synapse, its effect is enhanced and extended. At the same time, both M- and H-cholinoreceptors are excited. In addition, the anticholinesterase agents themselves, in addition to the destruction of the enzyme, the cholinoreceptors are excited, and most of the drugs are more excited by M-cholinoreceptors, therefore the heart rate is agreed, an increase in the bronchi tone, myiosis (narrowing) of pupils, savory-strengthening of the secretion of salivary, sweat, bronchial, gastric glands, increasing the tone and intestinal peristals, bladder and biliary tract. The smaller number of drugs are more exhibiting n-cholinomimetic effects: the excitation of the CNS, the narrowing of the vessels and an increase in blood pressure.
Anticholinesterase reversible action.They associate cholinesterase for several hours, after which it is completely restored and the effects of acetylcholine decreases. They are more often used in medical practice:
Fizostigmine and Galanamin It is well penetrated through the BC, therefore they are prescribed under the defeats (braking) of the CNS activities, after the injuries, strokes, poliomyelitis suffered.
Fizostigminalkaloidcalabar beans seeds of the West African Plant Physostigma Venenosum. FV: Powder for cooking droplets 0.25% -1% solution , When glaucoma reduces to / eye pressure when the pilocard is not effective. For treating b. Alzheimer (imperative of the subject memory), with progressive dementia, is used in a complex with nootropic means.
Galanaminalcaloid of Snowdrop of Voronov Calanthus Woronovi in \u200b\u200bother types of snowdrop . Release form:0.1%, 0.25%, 0.5% and 1% solutions in ampoules 1 ml, n / k ,
With residual phenomena after polio, stroke, the injuries of the CNS, to accelerate and alleviate the cholinergic transmission in the peripocal zones of persistent braking.
Prezero, Oksazil, Pyridostigmin, Distigminon the contrary, they do not penetrate the BC, they are used for postoperative intestinal and stomach. Prezerosynthetic substance , tablets of 0.015, eye drops 0.5%, 0.05% solution in ampoules., P / k. Inside taking a tablet 2-3 times a day. Under the bowel and bladder atony, to increase muscle tone (deuffinization) after the Mioroxification of tubocraran in anesthesiology; Miasthenia, paralysis cross-striped muscles. "Ubollid" distigmin,preparation more long actionapplied in the same way 0. 05% solution in ampoules 1 ml, in / m, 0.5 mg tablets inside 1 time per day or 1 time in 2-3 days. The overall excitation and M- and H-cholinoreceptors cause a lot side Effects, Therefore, anticholinesterase is combined with m-cholinoblockers (atropine), in carefully selected doses, to eliminate M-cholinomimetic effects. Contraindications: Bronchial asthma, organic heart disease, blockades in a conductive system.
Anticholinesterase irreversible action.
It is irreversible blocking the cholinesterase, excluding the cholinergic control over the functions of the body. Not used in medicine. With the exception of the drug " Armin ", Eye drops, 0.01% solution for glaucoma treatment.
FOS (phosphorus-organic) chlorofos, dichlofos is Highly efficient household insecticides. FOOD (phosphorganic poisoning substances), chemical attack Tabun, ZarinCurrently, their development and use is prohibited by the International Convention.
Picture of phos poisoning (anticholinesterase irreversible action): myiosis, sowing glands, breathing difficulty to bronchospasm, braking CNS replaces convulsive attacks, hypotension, spastic reductions of the gastrointestinal tract, vomiting, diarrhea, abdominal pain, death comes from an acute respiratory disorder. First aid: Introduction of M-cholinoblocators, for example, solution Atropine Sulfat p / k, or Holinesterase reactivators " Dipiroxim "," Isonitrosis ".
Control questions for fixing:
1. What caused M- and H-cholinoreceptors were allocated?
2. What symptoms occur during the poisoning of the amicer? What are the aid measures?
3. What symptoms occur during chlorophos poisoning? What are the aid measures?
4. In which plants contain substances of cholinomimetic action?
5. Does the combined preparations use pilocarpine hydrochloride?
6. Why are Lobelin and Cytiton solutions can be administered to the body only intravenously?
Recommended literature:
Mandatory:
1.V.M.Vinogradov, E.B. Katova, E.A. Mukhin "Pharmacology with recipe", a textbook for pharmaceutical schools and colleges / edited by V.M. Vinogradov-4 ed. IPR.- SPB.: SPEC. Lit., 2008-864c.: Il.
Additional:
1. Ppm Gaevy, P.A. Galenko - Yaroshevsky, V.I. Petrov, L.M. Gauge "Pharmacology with recipe": tutorial. - Rostov N / D: Mart Publishing Center, 2008 - 480s.
2.m.d. Mashkovsky "Medicines" - 16 ed., Recycled .. Act. And add.-m.: New Wave: Publisher of Demoles, 2010.- 1216 p.
3. Directory of Vidal, Medicinal preparations in Russia: Handbook. M.: Astrafarmservis, 2008.- 1520С.
4.ATLAS drugs. - M.: Sia International Co., Ltd. TF World: Publishing House Eksmo, 2008. - 992 p., Il.
5. N.I. Fedyukovich PU Directory medicinal preparations: at 2 h. C. P .. - MN: INTERPRESERVIS; Book House, 2008 - 544 p.
6.D.A. Kharekevich Pharmacology with general recipe: Textbook for medical schools and colleges. - M: Gootar - Honey, 2008, - 408 p., Il.
Electronic resources:
1.Electronic library on discipline. Lecture on "Holinomimetics".
6. M-Holinomimetics.
Localization M. 1
Localization: CNS neurons, sympathetic postganglionic neurons, some presynaptic zones.
Pharmacological effects in stimulation:
a) Activation of muscle plexus gasts
b) the activation of the sweat glands
Localization M. 2 -Holinoreceptors and pharmacological effects in their stimulation.
Localization: myocardium, gmk, some presynaptic zones
Pharmacological effects in their stimulation: Reducing the excitability of the node and a decrease in the reduction of the heart
Localization M. 3 -Holinoreceptors and pharmacological effects in their stimulation.
Localization: Ecocrine glands, vessels (MMC and endothelium)
Pharmacological effects when stimulating them:
Rainbow - Reducing the circular muscle (m 3-HR)
Cylier muscle - reduced (m 3-HD)
2) MMC vessels:
Endothelium - allocation of the endothelial relaxing factor NO (M 3-HD)
3) bronchiolar MMC: reduced (m 3-HD)
MMC Walls - Reduced (M 3-HD)
GMK Sphynbters - Relax (M 3-HD)
Secretion - rises (m 3-HD)
5) GMK of the urogenital system:
Bladder walls - reduced (m 3-HD)
Sphinteer - relax (m 3-HD)
The uterus during pregnancy is reduced (m 3-HD)
preparations from group M-Holinomimetics.
Pilocarpine, aceclidine.
mechanisms of action and pharmacological effects of M-Holinomimetics.
Mechanism of action: Stimulation M-XP.
Pharmacological effects of m-cholinomimetics:
Reduction m. Constrictor Pupillae.
The narrowing of the pupil (MIOS)
Opening an angle of the anterior chamber eye
Improved fluid outflow in channel helmets
Reducing the ciliary muscles and improving the outflow of intraocular fluid through the trabecular network
Increase curvature crustal (near focus)
2. Action on the CCC:
Reduced heart rate
Reducing atrioventricular conduction
Reducing heart rate
Peripheral vasodyolating (mediated through incompatible M-XP and the release of NO)
3. GCC: Increase the tone and amplitude of intestinal cutting
4. Bubble: Reduction of Destroyer, Reducing the Bladder Tank.
5. Matter: person is not sensitive to M-agonists.
6. Respiratory system:
Absolition of the muscles of the bronchial tree
Increasing the secretion of bronchial glands
7. CNS: Parkinginson-like effects.
side effects of m-cholinomimetics.
Under the local application:
1) Headache
2) follicular conjunctivitis, contact dermatitis of the eyelids
3) strong narrowing of pupil
4) Injection of vessels, lubricants and gravity in the eye. When taking inside:
1) nausea, vomiting
2) diarrhea or constipation, gastralgia, digestion disorders
3) chills, strengthening
4) frequent urination
5) Toothing, Rinorea
6) impairment of vision, dizziness, headache, burning heat to face, increase hell
basic indications and contraindications to use M-cholinomimetics.
Indications:
bladder Atonia, associated with neurogenic disorders
athony Musculature Zhkt.
reduced tone and submissive uterus, to stop bleeding in the postpartum period
as a diagnostic tool with radiological examination of the esophagus, stomach and duodenum
to narrow the pupil and reduce intraocular pressure during glaucoma or diseases leading to it (central veins thrombosis of the retina)
to narrow the pupil after instillation of mydriatics
gypofunction of salivary glands accompanied by dry oral mucosa
Contraindications:
eye diseases under which myiosis is unwanted, closedian glaucoma
bronchial asthma
pregnancy, lactation (except for use to increase the tone of myometrium)
increased sensitivity to m-cholinomimetics
chronic heart failure II-III stage, angina
bleeding from the gastro
epilepsy
Pilocarpin (Pilocarpinum).
Alkaloid extracted from Plant Pilocarus Pinnatifolius Jahorandi growing in Brazil.
Pilocarpini hydrochloride (Pilocarpini Hydrochloride) is used in medical practice.
Synonyms: Pilocrpinum Hydrochloridum, Pilocar.
Pilocarpine excites peripheral M-cholinoreceptors, causes an increase in the secretion of digestive and bronchial glands, a sharp increase in sweating, the narrowing of the pupil (with a simultaneous decrease in intraocular pressure and improved tissue trophics), an increase in the tone of smooth muscles, bronchi, intestines, gall and bladder, uterus. Pilocarpine antagonists are atropine and other M-cholinolithic agents.
When taking inside, the pylocarpine is quickly absorbed, however, PER OS is usually not prescribed. When instilled in the conjuncting bag of the eye, it is not enough in conventional concentrations and has no pronounced systemic effect.
Pilocarpine is widely used in ophthalmological practice to reduce intraocular pressure at glaucoma, as well as to improve the trophic eyes during thrombosis central Vienna retina, acute impassability of the artery of the retina, during atrophy spectator nerve, with hemorrhages in the vitreous body.
Pilocarpines are also used to stop the mydritic effect after the use of atropine, homatropine, scopolamine or other cholinolitic substances to expand the pupil with ophthalmic studies.
Pilocarpine prescribed aqueous solutions; solutions with the addition of polymer compounds (methylcellulose, etc.), which have a prolonged action; Ointment and special films made of polymeric material containing pylocarpine.
Pilocarpine is often used in combination with other drugs that reduce intraocular pressure: ~ -adrenoblockers (see Timolol), adrenomimetics, etc.
Eye films with pylocarpine are appropriate to assign in cases when it takes more than 3-4 to normalize the tone of the eyeball, one-time buckling of pylocarpine solutions per day. The film is layered with an eye tweezers for the lower eyelid 1 - 2 times a day. Wetting the tear fluid, it swells and is held in the lower conjunctival arch. Immediately after laying the film, the eye should be kept in a fixed state for 30 - 60 s, while wetting the film and switch it to a soft (elastic) state.
Aceclidine (Aceclidinum). 3-acetoxychinuclear salicylate.
Synonyms: ACeclidine, Glaucstat (hydrochloride), glauudin, glauunorm.
It is a cholineimetic substance that stimulates predominantly cholinoreactive systems of the body.
According to the chemical structure, the aceclay refers to 3-oxychinuclearididine derivatives (see also oxylidine, hasten, panenemin).
It relates it to the acetylcholine molecule and creates conditions for the binding of aceclidine with cholinoreceptors.
In contrast to acetylcholine, aceclay is not a quaternary, but tertiary basis, which ensures the possibility of penetration of aceclidine through histohematic barriers, including through the blood-brain barrier.
When administered to the organism, aceclidine causes an increase in the function of organs having cholinergic innervation. Particularly expressed the ability of the drug to increase the tone and strengthen the reducing the intestines, the bladder, the uterus. At higher doses there may be bradycardia, a decrease arterial pressure, reinforcement of savory, bronchio-acid. The drug has a strong Miotic effect; The narrowing of the pupil is accompanied by a decrease in intraocular pressure. The action of aceclidine is removed and prevented when the use of atropine and other cholinolistic substances.
The drug is easily absorbed at different ways of administration, including when instilled in a conjunctival bag.
Aceclay is used mainly as a means that warns and eliminating the atron of the bladder, especially with an increase in the amount of urine associated with the neurogenic urinary bubble disorders, during the atony of the muscles of the gastrointestinal tract, as well as in obstetric and gynecological practice - with a reduced tone and the submissions of the uterus, To stop bleeding in the postpartum period.
In ophthalmological practice, aceclidine solutions are used to narrow the pupil and reducing intraocular pressure during glaucoma.
Aceclay is a valuable pharmacological agent for an x-ray examination of the esophagus, stomach and duodenum. To identify the ahalasia of the esophagus caused by parasympathetic denervation. To clarify the nature of the lesions of the stomach and duodenum.
Aceclay is not inferior to morphine, does not have side effect.
In the ophthalmological practice, the aceclidine is prescribed in the form of eye drops.
Aceclay can be used in combination with other Miotics. 5% solution can be used to remove the mydriasis caused by homatropine; With mydriase from atropine and scopolamine aceclidine is not effective enough.
In therapeutic doses, aceclidine is well tolerated. In some cases, with the introduction of a solution in a conjunctival bag, a small irritation of conjunctivations may appear, the injection of vessels; Sometimes unpleasant subjective sensations (lubrication and severity in the eye) are developing. These phenomena pass on their own. Also, after the use of other Miotic tools, it is recommended after the aceclidine to press the field of a lacrimal bag to prevent the solution in tooth canal And the cavity of the nose.
Under the overdose of aceclidine (when used in the form of injections) or at elevated individual sensitivity, salivation, sweating, diarrhea and other phenomena associated with the excitation of cholinoreactive systems can be observed. These phenomena are quickly bought by the introduction of atropine, metacine or other cholinolithics.
The use of aceclidine is contraindicated in bronchial asthma, severe diseases of the heart, angina, bleeding from the gastrointestinal tract, epilepsy, hyperkinosis, during pregnancy (if the drug is not prescribed to increase the tone of the muscles of the uterus), as well as with inflammatory processes in abdominal cavity to surgical intervention.
M-, n-cholinomimetics
I. M-, N-cholinomimetically
Acetylcholine
Karbicholin.
II. M-cholinomimetic means (anticholinesterase agents, AHE)
a) reversible action
Prezero - Galanamin
Fizostigmine - Oxazil
Edrophonium - pyridostigmine
b) irreversible action
Phosphall - Armin.
Insecticides (chlorofos, carboofos, dichlorofos)
Fungicides (pesticides, defoliants)
Combat Poisoning Substances (Zarin, Zaman, Tabun)
III. M-cholinomimetics
Pilocarpin
Aceclidine
Muskarin
IV. M- cholinoblocators (preparations of the group atropine) a)
leaky
Atropine - Skopolamine
Platifillain - Metacin
b) selective (M-one - cholinoblocators)
Pyrezipin (Gastrepypin)
V. n-cholinomimetics
Cytithon
Lobelin
Nicotine
Vi. N-cholinoblocators
a) ganglioblocators
Benzohexonium - pyrine
Gigroniography - Arfonad
Pentamine
b) Miorlaxanta
Tubokurarine - Panteroniya
Anatruconium - Ditilin
We will analyze a group of funds related to M-, H-Holinomimetics. The means directly stimulating M- and Holinoreceptors (M-, H-Holinomimetics) include acetylcholine and its analogues (carbacholine). Acetylcholine, is a mediator in cholinergic synapses, is a choline ester and acetic acid and refers to monochrutic ammonium compounds.
It is practically not used as a medicinal product, as it acts sharply, quickly, almost lightningly, very briefly (minutes). When taking inside it is ineffective, as it is hydrolyzed. In the form of chloride, acetylcholine is used in experimental physiology and pharmacology.
Acetylcholine has a direct stimulating effect on M- and N -holinoreceptors. With systemic action of acetylcholine (in / in Introduction is unacceptable, because the blood pressure is sharply reduced) M-cholinomimetic effects are dominated: bradycardia, extension of blood vessels, increase the tone and contractual activity of the muscles of bronchi, gastrointestinal tract. The listed effects are similar to what is observed in irritation of the corresponding cholinergic (parasympathetic) nerves. The stimulating effect of acetylcholine on the N-cholinoreceptors of vegetative ganglia also takes place, but it is masked by a M-cholineimometric effect. Acetylhlin causes a stimulating effect on H-cholinoreceptors of skeletal muscles.
M-cholinomimetics in medical practice are most widely used: Pilocarin 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 pylocarpine), aceclidine (ACECLIDINUM) - AMM. - 1 and 2 ml of 0, 2% of RR; 3% and 5% - eye ointment.
Pilocarpine is an alkaloid from the Pilocarpus Microphyllus shrub, (South America). Currently obtained synthetically. It has a direct M-cholinomimetic effect.
Stimulating effector organs receiving cholinergic innervation, M-cholinomimetics cause effects similar to those observed in irritation of vegetative quinerity nerves. Especially greatly raises the pilocarpine secretion of glands. But the pylocarpine, being a very strong and toxic drug, is applied only in eye practice when glauer. In addition, pylocarpines are used during retinal vessels. Used locally, in the form of eye drops (1-2% r-p) and eye ointment (1 and 2%) and in the form of eye films. He narrows the pupil (from 3 to 24 hours) and reduces intraocular pressure. In addition, the accommodation spasm causes. The main difference from AHE funds is that the pylocarpine has a direct effect on the M-cholinrpecotors of the eye muscles, and the AHE means mediated.
Aceclidine (ACeclidinum) - synthetic M-cholinomimetics of direct action. Less toxic. Apply for local and resorbative action, that is, they are used both in eye practice and with general impact. Aceclidine is prescribed under glaucoma (a little annoying by a conjunct), as well as atomic gastrointestinal tract (in the postoperative period), bladder and uterine. In parenteral administration, there may be side effects: diarrhea, sweating, salivament. Contraindications: bronchial asthma, pregnancy, atherosclerosis.
H-cholinomimetics or means that stimulate nicotine-sensitive cholinoreceptors. This group includes alkaloids: nicotine, labeline and cytizin (cytifiton).
Since Nicotine therapeutic value does not submit, we will stop your attention on the 2nd Line Holinomimetics (Lobeline and Citizen).
We will analyze the preparation of Cytitonum (AMP. Pores 1 ml), representing 0, 15% citisin solution. Cytician itself is an alkaloid of the Raktnik plant (Cytisus Laburnum) and thermopsis (Termopsis Lanceolata). The feature of the drug of cytiton is that it is more or less selectively exciting H-cholinoreceptors of carotid glomes and the brain layer of adrenal glands, without acting on the other H-cholinoreceptors. The respiratory center is rapidly excited, the level of blood pressure rises.
Use a cytithon when stimulating a dummy center when it is in depression. With the introduction of cytiton, as a means, reflexively exciting respiratory center, after 3-5 minutes there is an excitement of respiration and the rise of blood pressure by 10-20 mm Hg. Art., for 15-20 minutes.
The drug acts reflexively, peculiar, briefly. It is used to excite the respiratory center with the saved reflex excitability (to coma) of the respiratory center. It is currently used by one indication: with carbon monoxide poisoning (CO). Now, in essence, in the clinic it is the only testimony. In experimental pharmacology, used to determine blood flow rates.
There is a similar drug - Lobelini (Lobelini Hydrochloridum: AMP. 1% 1 ml). The action is exactly the same as cytiton, but somewhat weaker the latter.
Use both drugs to stimulate breathing. Introduced in / in (only, t. The effect is reflex). In addition, both alkaloids are used as the main components of drugs that facilitate dumping from smoking tobacco (cytisin in Tablex tablets, Lobelin - in the tablast "Lobesil"). Preparations of weak action. They will leak smoking they helped a minor number of persons.
The drugs of this group have a direct stimulating effect on the MSholinoreceptors located at the endings of postganglyonary parasympathetic nerve fibers. As a result, they reproduce the effects of acetylcholine, associated with the excitation of parasympathetic innervation: the narrowing of the pupil (MIOS), the accommodation spasm (the eye is installed on the near vision), the narrowing of the bronchi, abundant salivation, increase the secretion of bronchial, digestive and sweat glands, increase the motorcycle tract motor , increase the tone of the bladder, bradycardia.
Fig.7. The effect of cholinomimetics on the eye (the number of arrows is indicated intensity of the outflow of intraocular fluid)
Pilocarpine - alkaloid of plant origin. It is obtained synthetically produced in the form of pilocarpine hydrochloride. His effect is a decrease in intraocular pressure, used to treat glaucoma (increased intraocular pressure up to 50-70mm Hg. Art.). The use of pylocarpine causes the narrowing of the pupil due to the reduction of the circular muscle of the iris, facilitates the outflow of the fluid from the front chamber of the eye to the rear due to the reduction of the ciliary muscle. At the same time, the accompliament spasm is developed (the crystal curvature increases). (Fig.11).
Pilocarpine is applied locally, because It is pretty toxic. Used in glaucoma, in atrophy of the optic nerve, to improve the trophic eyes, etc. has a slight irritating effect. It is part of the combined eye drops "Fotyl", "Pilotim".
H - Holinomimetics
The sensitivity of n-cholinoreceptors of different localization to chemicals is non-etinakov due to the differences in their structure.
H-cholinomimetics (cititon, labeline) excite the n-cholinoreceptors of synolocarotide glomers, which leads to reflex stimulation of respiratory and vascular centers. There is an increase and deepening breathing. The simultaneous excitation of synaptic assemblies and adrenalines leads to increased adrenaline emissions and an increase in blood pressure.
Cyticon and Lobelin hydrochloride are respiratory stimulants of reflexive action and can be used in a reflex respiratory stop (carbon monoxide poisoning, drowning, suffocation, electricians, etc.), during the asphyxia of newborns.
More widespread these substances are used to treat tobacco. As part of Tablex Tablets (Citizen) is used to facilitate dumping from smoking. For this purpose, low doses of nicotine are also used (Nikorette chewing gum, nicotinell plaster). These medicinal products Reduce physical dependence on nicotine.
Alkaloid tobacco - nicotine is also n-cholinomimetics, but as an LAN is not used. Penetrates the body during smoking tobacco and has a variety of action. Nicotine affects both peripheral and central n-cholinoreceptors, and possesses a two-phase effect: the first stage - excitement - is replaced by the oppressive effect. The constant effect of nicotine is its vasoconstrictor effect associated with the fact that nicotine stimulates n-cholinoreceptors of sympathetic ganglia, chromaphine cells of adrenal and synolocarotide zone, stimulates the selection of adrenaline and reflectically excites the vasomotor center. In this regard, nicotine increases blood pressure and promotes development hypertensive disease. Heavy vascular disease lower extremities - Supporting endarterite - it is found almost exclusively in smokers. Nicotine narrows heart vessels and promotes the development of angina, myocardial infarction, tachycardia. Serious changes are observed by the CNS. Shows nicotine and carcinogenic effect.
M, n - cholinomimetics
These substances simultaneously stimulate M- and n-cholinoreceptors and directly or indirectly affect the executive bodies. Differ M, n-cholinomimetics direct and indirect action.
LAN direct action includes acetylcholine and carbacholin (carbachol). They directly stimulate postsynaptic receptors. As a medicament, acetylcholine is practically not used, because It acts briefly (a few minutes). It is used in experimental pharmacology.
In medical practice, an analogue of acetylcholine - carbacholin with glaucoma is sometimes used in the form of eye drops. It differs from acetylcholine greater resistance and acts longer (up to 1-1.5 hours), because It is not hydrolyzed by acetylcholineserase.
Anticholinesterase means (m, n - cholinomimetics of indirect action).
These substances inhibit the activity of the enzyme acetylcholinesterase and enhance the effect of acetylcholine on M- and H-cholinoreceptors. The effects of anticholinesterase agents are mainly similar to the effects of direct m, n-cholinomimetics. M-cholinomimetic effect manifests itself in increasing the tone and contractile activity of smooth muscles (bronchi, gastrointestinal tract, bladder, circular muscles of iris, etc.), in strengthening the secretion of glands (bronchial, digestive, sweat, etc.), in bradycardia and falling blood pressure. H-cholinomimetic effect is manifested in stimulation of neuromuscular conductivity. In small doses, anticholinesterase agents stimulate the CNS, and in large - inhibit.
Tertiary amines (physostigmine, galantamine) penetrate through biological membranes, including through the BC, and have a pronounced effect on the CNS. Quaternary ammonium derivatives (prozerne, pyridostigmine, distigmin) are difficult to penetrate the BGB.
Inhibition of acetylcholinesterase is carried out due to the interaction of substances with the same sections of the enzyme with which acetylcholine is associated. This connection can be reversible and irreversible.
Neostigmin (prozerne) - synthetic LS, is a quaternary ammonium compound, does not penetrate the BGB and has a preferential effect in peripheral tissues. It is used for miastic, muscle dystrophy, paralymps, motor disorders associated with neuritis, polyneuritis, residual phenomena after injuries of brain, poliomyelitis, meningitis, encephalitis, as well as in atony in the intestine and bladder, weak generic activity. Prezero is an antagonist of M-cholinoblocators and strip-like drugs with an antide-polarizing type of action. Contraindicated in epilepsy, bronchial asthma, angina, atherosclerosis, pregnancy.
Galanamin (Nivalin) is an alkaloid contained in the tubers of snowdrops. Available in the form of galantamine hydrobromide. It is a tertiary amine, penetrates through the BGB and has a central activity. Similar properties have Fizostigmin (Fisostigmine Salicylate).
It is used in polyneuritis, violations of cerebral circulation, polio, children's cerebral paralysis, dementia (memory violation), during myasthenia, internal organ athi.
Distigmine Bromide (ulitid), pyridostigmine Bromide (Calimine) - synthetic drugs, reversible inhibit acetylcholineserase. Applied in atony of intestines and bladder, myasthenia, paralysis of striped muscles.
Due to the phosphorylation of acetylcholinesterase, an irreversible oppression of its activity for a long time is carried out. Such actions have phosphorodorganic compounds (FOS), of which the medical use in the treatment of glaucoma acquired phosphares and armor in the form of eye drops.
But the FOS also includes a large group of insecticides used to destroy insects (chlorophos, carbofos, dichlofos, etc.), as well as fungicides, herbicides, etc. used in agriculture.
When they are used, poisoning often occur, having the following symptoms: MIOS (narrowing of the pupil), saliva, sweating, vomiting, bronchospasm, diarrhea. Clear, psychomotor arousal, coma and stop breathing may occur. In case of acute phos poisoning, first of all, it is necessary to remove the poisoning substance from the place of administration, the skin cover was rinsed with a 3-5% sodium hydrocarbonate solution. If you get a floss inside - rinse the stomach, give laxative and adsorbing agents. If the FOS entered blood, then forced diuresis, hemosorption, hemodialysis.
As functional antagonists, m-cholinoblockers (atropine et al.), As well as Holinesterase reactivators - dipiroxim and isonitrosin are used. They bind to the FOS, destroy the phosphorus-enzyme communications and restore the activity of the enzyme. These LS are effective only in the first hours after poisoning.
Cholinoblochetics
Choline-blocking or anticholinergic agents call substances that weaken, prevent or stopping the interaction of acetylcholine with cholinoreceptors. Blocking receptors, they act oppositely acetylcholine.
M - cholinoblocators
The drugs of this group are blocked by M - cholinoreceptors and impede the interaction with them acetylcholine mediator. It eliminates (blocked) parasympathetic innervation of organs and appropriate effects arise: decrease in the secretion of salivary, sweat, bronchial, digestive glands, the expansion of the bronchi, the decrease in the tone of smooth muscles and the peristals of the internal organs, tachycardia and the strengthening of heartbreaks; Under the local application, the expansion of the pupil (MIDRIAZ), the accommodation paralysis (vision is installed on a far vision), an increase in intraocular pressure.
Non-selective M - Holy Blockers
They affect the peripheral and central M-cholinoreceptors. Among them are produced vegetable and synthetic drugs.
Atropine is the alkaloid of a row of plants from the Parenic family: beautification, dope, white and others. Released in the form of atropine sulfate. It is a racemate, represents a mixture of L- and D-isomers of the Hyoscyiamine. Get also a synthetic way. Call all the above effects. Safety spasmodic properties are especially expressed in atropine, eye effect, secretion of glands, conductive heart system. In large doses, atropin stimulates the cerebral bark and can cause motor and speech concern.
Apply atropine at ulcer of stomach and duodenal gut, in intestinal spasms and urinary tract, with bronchial asthma, in bradycardia and an atrioventricular blockade of the heart, with an increased sweating, to reduce salivation in Parkinson's disease, for premium in front of anesthesia due to its ability to suppress the secretion of salivary and bronchial glands, in the poisoning of M-cholinomimetics and anticholinesterase agents.
In the eye practice, atropine is used to expand the pupil with a diagnostic purpose and with acute inflammatory diseases and eye injuries. The maximum expansion of the pupil occurs after 30-40 minutes and lasts 7-10 days. The atropine-like dosage agents of homatopine (15-20 hours) and tropiacal (2-6 hours) are less continuous.
The undesirable effects of atropine are associated with its M-choline-blocking effect: dryness of the mouth, leather, violation of vision, tachycardia, change in voice, violation of the uriction, constipation. Reducing the sweating can lead to an increase in body temperature.
Atropine and m-cholinoblocators are contraindicated with glaucoma, increased sensitivity to them, during fever, in the hot season (due to the possibility of "heat strike").
In case of atropine poisoning, dryness of the oral mucosa, nasopharynx, swallowing, speech is noted; dryness and hyperemia of the skin, increasing body temperature, expansion of pupils, photophobia (light-free). Sophisticated motor and speech arousal, nonsense, hallucinations.
Poisoning occurs in the overdose of drugs or when eating parts of a plant containing alkaloids. Assistance in acute poisoning is to wash the stomach, the use of salt laxative, activated carbon, diuretics. With pronounced excitation, diazepams and other means of oppressive CNS are used. Functional antagonists from the group of anticholinesterase products are also introduced - Fizostigmin Salicylate.
From drugs containing atropine, prepressing preparations (belladone) are also used, obtained from the leaves and the grass of this plant. Tablet's tincture, pills "Bekarbon", Blessing, "Bepasal", "Bellalgin", "Bellatesin" are used in spasmodic pains of the gastrointestinal tract. Handicker extract is part of the Bethiol candles, anusol used in the hemorrhoids and the cracks of the rear passage. Tablets "Bellataminal", "Bellaspon", containing the sum of the alkaloids of beautification, are used with elevated irritability, neurosis, etc.
Skptolamine (hyoscium) is an atropine-like alkaloid of the same plants. Has pronounced M-choline-blocking properties, has more strong action on the eye and secretion of glands. Unlike atropine, the CNS oppresses, causes calm and drowsiness, acts on the extrapyramid system and the vestibular apparatus. Released in the form of a scopolamine hydrobromide.
It is applied according to the same indications as the atropine, as well as during sea and aerial disease (part of the Tablets "Aeron"). The air-sea, locomotive also possess the anti-anemic effect.
Platifillin - the alkaloid of a cross-line. Used in the form of hydrotathe salts. It has a more pronounced peripheral antispasmodic effect. Apply mainly in the spasms of the stomach, intestines, biliary tract, ureters.
Metocynes Iodide (metacin) - synthetic M-cholinoblocator. It does not penetrate the hematostephalic barrier, it does not affect the CNS. According to the effect on the bronchial muscles, it is more active than atropine, stronger suppresses the secretion of salivary and bronchial glands. Relaxes the muscles of the esophagus, intestines, stomach, but has a significantly less mydritic effect than atropine.
Metacin is used in smooth muscle spasms. Effective when killing renal and liver colic. Unwanted side effects appear less often.
Selective M - cholinoblocators
Pyrenspine (gastrozepin, gastroin) selectively blocks M1-cholinoreceptors of the stomach and suppresses the secretion of hydrochloric acid. Applied for ulcerative diseases of the stomach and duodenum, hyperacid gastritis. Unwanted side effects are rarely manifested: dry mouth, dyspeptic phenomena, easy violation of accommodation. Contraindicated in glaucoma.
Hypratropy Bromide (Atrovant), Tiotropi Bromide (Spiriva) - Block M-cholinoreceptors of bronchi, have a bronchological effect, reduce the secretion of glands. Applied with bronchial asthma. IPratropy is part of the combined aerosols "Berodual", "Combivent". Unwanted side effects: dry mouth, increased sputum viscosity, allergic reactions.
H - cholinoblocators
This group includes gangli-blocking agents and blockers of neuromuscular synapses.
Ganglioblocators
These substances block n-cholinoreceptors of vegetative ganglia, brainstant of adrenal glands, synolocarotide zone. At the same time, n-cholinoreceptors of sympathetic and parasympathetic nerves are blocked at the same time. Due to the oppression of the sympathetic ganglia, the transfer of impulses to the blood vessels is disturbed, as a result of which the vessels are expanding, arterial and venous pressure decreases. The expansion of peripheral vessels leads to improved blood circulation in them. When the blockade of parasympathetic ganglia decreases the secretion of the glands (sweat, salivary, digestive), the muscles of the bronchi relaxes, the motorbate of the digestive tract is slowed down.
Hexametonium (benzenexonium) is a quartered ammonium compound, has a strong gangli-blocking activity. More active in parenteral administration. It is used in snapshams of peripheral vessels (endarterite, Reino disease, etc.), for controlled hypotension during operations, in the edema of the lungs, the brain (against the background of increased blood pressure), less often - with ulcer of the stomach, bronchial asthma, intestinal spasms, etc., Hypertension.
When administered hexametonia and other gangliplockers, the orthostatic collapse is possible. For its prevention, the patients are recommended for 1-2 hours after the injection of the gangliplocker is in the lying position. At the phenomena of the collapse should be introduced -adrenomimetic.
When using benzenexonia is also possible total weakness, dizziness, dry mouth, tachycardia, expansion of pupils, inhibition of breathing, constipation, urination disorder.
LANs are contraindicated in hypotension, with myocardial infarction in the acute stage, with damage and liver damage, during thrombosis, degenerative changes in the central nervous system. Caution is needed at appointments of elderly.
Trepium iodide (hygros) and trimetafan (arfonad) have a short-term gangli-blocking effect. Used for controlled hypotension and to relieve hypertensive crises. They introduce them to Vienna drip.
Currently, gangliplockers are rarely applied.
Miorolaksanta (from Greek - Mys - muscles, lat. - Relaxio - weakening) (strip-like)
The drugs of this group selectively block n-cholinoreceptors in neuromuscular synapses and cause relaxation of skeletal muscles. They are called string-like means by the name of the rocky poison "Kurara" used by the Indians during the hunt for animal immobilization.
According to the mechanism of action, two groups of minelaxants distinguish: non-compolant (antide-polarizing) and depolarizing.
Most of the drugs are antidehaming. They interact with n-cholinoreceptors of the postsynaptic membrane of neuromuscular synapses and prevent the depolarizing action of acetylcholine. Their antagonists are anticholinesterase agents (neostigmin, galanamine): the activity of cholinesterase in the respective doses, they contribute to the accumulation of acetylcholine synapses, with an increase in the concentration of which the interaction of strip-like substances with H-cholinoreceptors weakens and neuromuscular conductivity is restored. These include Tubokuarina chloride, diplocine, punchonia bromide (Pavlon), Pipecuronia Bromide (Ardaun), etc. These drugs are used to relax muscles during surgery, when the tracheal is intubated, during the reposition of bone fragments, during cramps, tetanus, to order dislocation.
The stripping means relax muscles in a certain sequence: first the muscles of the face and neck relaxes, then the limbs and torso, the latter is the intercostal muscles and the diaphragm, which is accompanied by stopping the breath.
Another group of drugs - depolarizing muscle relaxants. They cause persistent depolarization of the postsynaptic membrane, while repolarization occurs and the subsequent impulses do not pass. LS of this group relatively quickly hydrolyzed by cholinesterase and in one-time introduction they have a short-term action. They do not have antagonists. Such an LAN is suucameonia chloride (dithiline, leafenon). He is introduced into Vienna. He quickly and briefly relaxes a skeletal muscles. For longer muscle relaxation is necessary repeated administration Hp.
When using muscle relaxants of both groups, as a rule, paralysis of respiratory muscles is developing, so their use is allowed only if there are conditions for artificial respiration.
Of unwanted side effects, a decrease in blood pressure and bronchospasm is sometimes noted. It is contraindicated in miastic, with caution, it is necessary to use when the function of the kidneys and the liver is violated, as well as in high age.
M, n - cholinoblocators
These drugs have a peripheral and central mbolin-blocking effect. Central action helps to reduce or eliminate motor disorders (tremor, rigidity) associated with the damage to the extrapyramid system. Widespread use was received by trihexiphenidyl (cyclodol, Paropean) in the treatment of Parkinson's disease. When using drugs may occur sideflinesassociated with its cholinolic properties: dry mouth, accommodation violation, pulse, dizziness. LS is contraindicated with glaucoma, heart diseases, elderly people.
