Main pharmacological effects of atropine. How to correctly use atropine for complex treatment Atropine farm action

1. Atropine has especially pronounced antispasmodic properties. By blocking M-cholinergic receptors, atropine eliminates the stimulating effect of parasympathetic nerves on smooth muscle organs. The tone of the muscles of the gastrointestinal tract, bile ducts and gallbladder, bronchi, ureters, and bladder decreases.

2. Atropine also affects the tone of the eye muscles. Let's look at the effects of atropine on the eye:

a) when atropine is administered, especially when applied topically, due to a block of M-cholinergic receptors in the circular muscle of the iris, pupil dilation is noted - mydriasis. Mydriasis also intensifies as a result of the preservation of the sympathetic innervation of m. dilatator pupillae. Therefore, atropine acts on the eye for a long time in this regard - up to 7 days;

b) under the influence of atropine, the ciliary muscle loses its tone, it becomes flattened, which is accompanied by tension in the ligament of Zinn, which supports the lens. As a result, the lens also flattens, and the focal length of such a lens lengthens. The lens sets vision to the far point of vision, so nearby objects are not clearly perceived by the patient. Since the sphincter is in a state of paralysis, it is not able to constrict the pupil when viewing nearby objects, and photophobia (photophobia) occurs in bright light. This condition is called ACCOMMODATION PARALYSIS or CYCLOPLEGIA. Thus, atropine is both a mydriatic and a cycloplegic. Local application of a 1% atropine solution causes a maximum mydriatic effect within 30-40 minutes, and complete restoration of function occurs on average after 3-4 days (sometimes up to 7-10 days). Paralysis of accommodation occurs within 1-3 hours and lasts up to 8-12 days (approximately 7 days);

c) relaxation of the ciliary muscle and displacement of the lens into the anterior chamber of the eye is accompanied by a violation of the outflow of intraocular fluid from the anterior chamber. In this regard, atropine either does not change intraocular pressure in healthy individuals, or in individuals with a shallow anterior chamber and in patients with narrow-angle glaucoma, it may even increase, that is, lead to an exacerbation of an attack of glaucoma.

INDICATIONS FOR THE USE OF ATROPINE IN OPHTHALMOLOGY

1) In ophthalmology, atropine is used as a mydriatic to cause cycloplegia (paralysis of accommodation). Mydriasis is necessary when examining the fundus of the eye and in the treatment of patients with iritis, iridocyclitis and keratitis. In the latter case, atropine is used as an immobilization agent that promotes functional rest of the eye.

2) To determine the true refractive power of the lens when selecting glasses.

3) Atropine is the drug of choice if it is necessary to achieve maximum cycloplegia (paralysis of accommodation), for example, when correcting accommodative strabismus.

3. INFLUENCE OF ATROPINE ON ORGANS WITH SMOOTH MUSCLE. Atropine reduces the tone and motor activity (peristalsis) of all parts of the gastrointestinal tract. Atropine also reduces peristalsis of the ureters and the bottom of the bladder. In addition, atropine relaxes the smooth muscles of the bronchi and bronchioles. In relation to the biliary tract, the antispasmodic effect of atropine is weak. It should be emphasized that the antispasmodic effect of atropine is especially pronounced against the background of a previous spasm. Thus, atropine has an antispasmodic effect, that is, atropine acts in this case as an antispasmodic. And only in this sense can atropine act as a “painkiller”.

4. INFLUENCE OF ATROPINE ON THE ENDOCRECTION GLANDS. Atropine sharply weakens the secretion of all exocrine glands, with the exception of mammary glands. In this case, atropine blocks the secretion of liquid watery saliva caused by stimulation of the parasympathetic part of the autonomic nervous system, causing dry mouth. Tear production decreases. Atropine reduces the volume and overall acidity of gastric juice. In this case, suppression and weakening of the secretion of these glands can be up to their complete shutdown. Atropine reduces the secretory function of glands in the cavities of the nose, mouth, pharynx and bronchi. The secretion of the bronchial glands becomes viscous. Atropine, even in small doses, inhibits the secretion of SWEAT GLANDS.

5. INFLUENCE OF ATROPINE ON THE CARDIOVASCULAR SYSTEM. Atropine, taking the heart out of control n. vagus, causes TACHYCARDIA, that is, it increases the heart rate. In addition, atropine helps facilitate the conduction of impulses in the conduction system of the heart, in particular in the AV node and along the atrioventricular bundle as a whole. These effects are less pronounced in elderly people, since in therapeutic doses atropine does not have a significant effect on peripheral blood vessels; their tone is reduced. vagus Atropine does not have a significant effect on blood vessels in therapeutic doses.

6. INFLUENCE OF ATROPINE ON THE CNS. In therapeutic doses, atropine has no effect on the central nervous system. In toxic doses, atropine sharply excites the neurons of the cerebral cortex, causing motor and speech excitation, reaching mania, delirium and hallucinations. The so-called “atropine psychosis” occurs, leading further to a decrease in functions and the development of coma. It also has a stimulating effect on the respiratory center, but with increasing doses, respiratory depression may occur.

INDICATIONS FOR USE OF ATROPINE (except ophthalmological)

1) As an ambulance for:

a) intestinal

b) renal

c) hepatic colic.

2) For bronchospasms (see adrenergic agonists).

3) In complex therapy of patients with peptic ulcer of the stomach and duodenum (reduces the tone and secretion of the glands). It is used only in a complex of therapeutic measures, since it reduces secretion only in large doses.

4) As a presedation agent in anesthesiological practice, atropine is widely used before surgery. Atropine is used as a means of drug preparation of a patient for surgery because it has the ability to suppress the secretion of the salivary, nasopharyngeal and tracheobronchial glands.

As is known, many anesthetics (ether in particular) are strong irritants of the mucous membranes. In addition, by blocking M-cholinergic receptors of the heart (the so-called vagolytic effect), atropine prevents negative reflexes on the heart, including the possibility of its reflex stop.

By using atropine and reducing the secretion of these glands, the development of inflammatory postoperative complications in the lungs is prevented. This explains the importance of the fact that resuscitation doctors attach when they talk about the full opportunity to “breathe” the patient.

5) Atropine is used in cardiology. Its M-anticholinergic effect on the heart is beneficial in some forms of cardiac arrhythmias (for example, atrioventricular block of vagal origin, that is, with bradycardia and heart block).

6) Atropine has found widespread use as an ambulance for poisoning:

a) AChE means (FOS)

b) M-cholinomimetics (muscarine).

Along with atropine, other atropine-like drugs are well known. Natural atropine-like alkaloids include SCOPOLAMINE(hyoscine) Scopolominum hydrobromidum. Available in ampoules of 1 ml - 0.05%, as well as in the form of eye drops (0.25%). Contained in the mandrake plant (Scopolia carniolica) and in the same plants that contain atropine (belladonna, henbane, datura). Structurally close to atropine. It has pronounced M-anticholinergic properties. There is one significant difference from atropine: in therapeutic doses, scopolamine causes mild sedation, central nervous system depression, sweating and sleep. It has a depressing effect on the extrapyramidal system and the transmission of excitation from the pyramidal tracts to the motor neurons of the brain. Introducing the drug into the conjunctival cavity causes less prolonged mydriasis.

Therefore, anesthesiologists use scopolomine (0.3-0.6 mg s.c.) as a premedication, but usually in combination with morphine (but not in the elderly, as it can cause confusion). It is sometimes used in psychiatric practice as a sedative, and in neurology for the correction of parkinsonism. Scopolamine has a shorter duration of action than atropine. They are also used as an antiemetic and sedative for sea and airborne illnesses (Aeron tablets are a combination of scopolamine and hyoscyamine).

The group of alkaloids obtained from plant materials (rhombolic ragwort) also includes PLATIFILLINE.(Platyphyllini hydrotartras: tablets of 0.005, as well as ampoules of 1 ml - 0.2%; eye drops - 1-2% solution). It acts in much the same way, causing similar pharmacological effects, but weaker than atropine. It has a moderate ganglion-blocking effect, as well as a direct myotropic antispasmodic effect (papaverine-like), as well as on the vasomotor centers. Has a calming effect on the central nervous system. Platiphylline is used as an antispasmodic for spasms of the gastrointestinal tract, bile ducts, gallbladder, ureters, with increased tone of the cerebral and coronary vessels, as well as for the relief of bronchial asthma. In ophthalmic practice, the drug is used to dilate the pupil (it has a shorter effect than atropine and does not affect accommodation). It is administered under the skin, but it should be remembered that solutions of 0.2% concentration (pH = 3.6) are painful.

Suggested for eye practice HOMATROPINE(Homatropinum: 5 ml bottles - 0.25%). It causes pupil dilation and paralysis of accommodation, that is, it acts as a mydriatic and cycloplegic. The ophthalmic effects caused by homatropine last only 15-24 hours, which is much more convenient for the patient compared to the situation when atropine is used. The risk of raising IOP is less, since atropine is weaker, but at the same time, the drug is contraindicated for glaucoma. Otherwise, it is not fundamentally different from atropine; it is used only in ophthalmic practice.

Synthetic drug METACIN- a very active M-anticholinergic blocker (Methacinum: in tablets - 0.002; in ampoules 0.1% - 1 ml. Quaternary, ammonium compound that poorly penetrates the BBB. This means that all its effects are due to the peripheral M-anticholinergic action .

It differs from atropine in having a more pronounced bronchodilator effect and no effect on the central nervous system. It suppresses the secretion of the salivary and bronchial glands more strongly than atropine. Used for bronchial asthma, peptic ulcer disease, for relieving renal and hepatic colic, for premedication in anesthesiology (iv - in 5-10 minutes, intramuscularly - in 30 minutes) - more convenient than atropine. The analgesic effect is superior to atropine and causes less tachycardia.

Among medicines containing atropine, belladonna (belladonna) preparations are also used, for example, belladonna extracts (thick and dry), belladonna tinctures, and combined tablets. These are weak drugs and are not used in ambulances. Used at home at the pre-hospital stage.

Finally, a few words about the first representative of selective muscarinic receptor antagonists. It turned out that in different organs of the body there are different subclasses of muscarinic receptors (M-one and M-two). Recently, the drug gastrocepin (pirenzepine) was synthesized, which is a specific inhibitor of M-one cholinergic receptors of the stomach. Clinically, this is manifested by intense inhibition of gastric juice secretion. Due to the pronounced inhibition of gastric juice secretion, gastrocepin causes persistent and rapid pain relief. Used for stomach and duodenal ulcers, gastritis, daudenitis. It has significantly fewer side effects and has virtually no effect on the heart and does not penetrate into the central nervous system.

SIDE EFFECTS OF ATROPINE AND ITS DRUGS.

In most cases, side effects are a consequence of the breadth of the pharmacological action of the drugs being studied and are manifested by dry mouth, difficulty swallowing, intestinal atony (constipation), blurred visual perception, and tachycardia. Topical use of atropine can cause allergic reactions (dermatitis, conjunctivitis, swelling of the eyelids). Atropine is contraindicated in glaucoma.

ACUTE POISONING WITH ATROPINE, ATROPINE-LIKE DRUGS AND PLANTS CONTAINING ATROPINE.

Atropine is far from a harmless drug. Suffice it to say that even 5-10 drops can be toxic. The lethal dose for adults when taken orally starts at 100 mg, for children - at 2 mg; When administered parenterally, the drug is even more toxic. The clinical picture of poisoning with atropine and atropine-like drugs is very characteristic. There are symptoms associated with the suppression of cholinergic influences and the effect of the poison on the central nervous system. At the same time, depending on the dose of the ingested medication, MILD and SEVERE courses are distinguished.

In case of mild poisoning, the following clinical signs develop:

1) dilated pupils (mydriasis), photophobia;

2) dry skin and mucous membranes. However, due to a decrease in sweating, the skin becomes hot and red, there is an increase in body temperature, and a sharp flushing of the face (the face is “bursting with heat”);

3) dry mucous membranes;

4) severe tachycardia;

5) intestinal atony.

In case of severe poisoning, against the background of all these symptoms, PSYCHOMOTOR Arousal comes to the fore, that is, both mental and motor arousal. Hence the well-known expression: “I’ve eaten too much henbane.” Motor coordination is impaired, speech is blurred, consciousness is confused, and hallucinations are noted. Phenomena of atropine psychosis are developing, requiring the intervention of a psychiatrist. Subsequently, depression of the vasomotor center may occur with a sharp expansion of the capillaries. Collapse, coma and respiratory paralysis develop.

HELP MEASURES FOR ATROPINE POISONING

If the poison is taken orally, then an attempt should be made to pour it out as quickly as possible (gastric lavage, laxatives, etc.); astringents - tannin, adsorbents - activated carbon, forced diuresis, hemosorption. It is important to apply specific treatment here.

1) Before washing, a small dose (0.3-0.4 ml) of sibazon (Relanium) should be administered to combat psychosis and psychomotor agitation. The dose of sibazon should not be large, as the patient may develop paralysis of vital centers.

In this situation, aminazine cannot be administered, since it has its own muscarinic-like effect.

2) It is necessary to displace atropine from its connection with cholinergic receptors; various cholinomimetics are used for these purposes. It is best to use physostigmine (iv, slowly, 1-4 mg), which is what they do abroad. We use AChE agents, most often prozerin (2-5 mg, s.c.). Medicines are administered at intervals of 1-2 hours until signs of elimination of the blockade of muscarinic receptors appear. The use of physostigmine is preferable because it penetrates well through the BBB into the central nervous system, reducing the central mechanisms of atropine psychosis. To alleviate photophobia, the patient is placed in a darkened room and rubbed with cool water. Careful care is required. Artificial respiration is often required.

N-CHOLINERGIC DRUGS

Let me remind you that H-cholinergic receptors are localized in the autonomic ganglia and end plates of skeletal muscles. In addition, H-cholinergic receptors are located in the carotid glomeruli (they are necessary to respond to changes in blood chemistry), as well as the adrenal medulla and the brain.

The sensitivity of H-cholinergic receptors of different localization to chemical compounds is not the same, which makes it possible to obtain substances with a predominant effect on the autonomic ganglia, cholinergic receptors of neuromuscular synapses, and the central nervous system.

Drugs that stimulate H-cholinergic receptors are called H-cholinomimetics (nicotinomimetics), and those that block them are called H-cholinergic blockers (nicotine blockers).

It is important to emphasize the following feature: all H-cholinomimetics excite H-cholinergic receptors only in the first phase of their action, and in the second phase the excitation is replaced by an inhibitory effect. In other words, N-cholinomimetics, in particular the reference substance nicotine, have a two-phase effect on H-cholinergic receptors: in the first phase, nicotine acts as an N-cholinomimetic, in the second - as an N-cholinergic blocker.

Included in the preparations

VED

A.03.B.A Belladonna alkaloids, tertiary amines

A.03.B.A.01 Atropine

VII.H15-H22.H16 Keratitis

VII.H15-H22.H20.0 Acute and subacute iridocyclitis

VII.H15-H22.H20.1 Chronic iridocyclitis

VII.H30-H36.H34 Retinal vascular occlusion

IX.I30-I52.I44 Atrioventricular [atrioventricular] block and left bundle branch block [His]

X.J00-J06.J05 Acute obstructive laryngitis [croup] and epiglottitis

X.J40-J47.J42 Chronic bronchitis, unspecified

XI.K20-K31.K26 Duodenal ulcer

XI.K20-K31.K25 Stomach ulcer

XI.K20-K31.K31.3 Pylorospasm, not elsewhere classified

XI.K55-K63.K58 Irritable bowel syndrome

XI.K80-K87.K80 Gallstone disease [cholelithiasis]

XI.K80-K87.K85 Acute pancreatitis

XIX.S00-S09.S05 Trauma to the eye and orbit

XIX.T36-T50.T48 Poisoning with drugs acting primarily on smooth and skeletal muscles and respiratory organs

Pharmacological.

The mechanism of action is due to the selective blockade of M-cholinergic receptors by atropine (it has a lesser effect on N-cholinergic receptors), as a result of which M-cholinergic receptors become insensitive to acetylcholine, which is formed in the area of ​​​​the endings of postganglionic parasympathetic neurons. The ability of atropine to bind to cholinergic receptors is explained by the presence in its molecule of a fragment that gives it affinity with the molecule of the endogenous ligand - acetylcholine. Atropine sulfate reduces the secretion of the salivary, bronchial, gastric and sweat glands, increases the viscosity of bronchial secretions, suppresses the activity of the cilia of the ciliated epithelium of the bronchi, thereby reducing mucociliary transport, accelerates heart contraction, increases AV conductivity, reduces the tone of smooth muscle organs, reduces the number and total acidity gastric juice (especially with the predominance of cholinergic regulation of secretion), reduces basal and nocturnal secretion of gastric juice, to a lesser extent reduces stimulated secretion, vira enno dilates the pupil (this may increase intraocular pressure). Penetrating the blood-brain barrier, atropine in therapeutic doses stimulates the respiratory center.

Pharmacokinetics.

After intravenous administration, the maximum effect appears within 2-4 minutes. Atropine sulfate is quickly absorbed into the bloodstream from the injection site. It is quickly distributed in the body, penetrates the blood-brain, placental barrier and into breast milk. In the blood, atropine is 50% protein bound, its volume of distribution is about 3 l/kg. After administration, the concentration of atropine in the blood plasma decreases in two stages. The first stage is fast - the half-life is 2:00. During this time, approximately 80% of the administered dose of atropine is excreted in the urine. The second stage - the rest of the drug is excreted in the urine - the half-life is 13-36 hours. Atropine is metabolized in the liver by enzymatic hydrolysis, approximately 50% of the dose is excreted unchanged by the kidneys.

Indications

As a symptomatic remedy for gastric and duodenal ulcers, pylorospasm, acute pancreatitis, cholelithiasis, cholecystitis, intestinal spasms, urinary tract spasms, bronchial asthma, bradycardia, as a result of increased tone of the vagus nerve, to reduce the secretion of salivary, gastric, bronchial, and sometimes sweat glands, for X-ray examination of the digestive system (decreased tone and motor activity of organs).

The drug is also used before anesthesia, surgery and during surgery as a means of preventing broncho and laryngospasms, reduces gland secretion, reflex reactions and side effects caused by excitation of the vagus nerve. As a specific antidote for poisoning with cholinomimetic compounds and anticholinesterase (including organophosphorus) substances.

Contraindications

Hypersensitivity to the components of the drug. Diseases of the cardiovascular system in which an increase in heart rate may be undesirable: atrial fibrillation, tachycardia, chronic heart failure, coronary heart disease, mitral stenosis, severe arterial hypertension. Acute bleeding. Thyrotoxicosis. Hyperthermic syndrome. Diseases of the digestive system accompanied by obstruction (achalasia of the esophagus, pyloric stenosis, intestinal atony). Glaucoma. Liver and kidney failure. Myasthenia gravis gravis. Urinary retention or predisposition to it. Brain damage.

Interaction with other drugs and other types of interactions

When using atropine sulfate with MAO inhibitors, cardiac arrhythmias occur; with quinidine, novocainamide, a summation of the anticholinergic effect is observed. When taken orally with lily of the valley preparations, a physicochemical interaction is observed with tannin, which leads to a mutual weakening of the effects.

Atropine sulfate reduces the duration and depth of action of narcotic drugs and weakens the analgesic effect of opiates.

When used simultaneously with diphenhydramine or diprazine, the effect of atropine increases; with nitrates, haloperidol, corticosteroids for systemic use - the likelihood of increasing intraocular pressure increases; with sertraline - the depressive effect of both drugs increases; with spironolactone, minoxidil - the effect of spironolactone and minoxidil decreases; with penicillins - the effect of both drugs is enhanced, with nizatidine - the effect of nizatidine is enhanced, ketoconazole - the absorption of ketoconazole is reduced, with ascorbic acid and attapulgite - the effect of atropine is reduced, with pilocarpine - the effect of pilocarpine in the treatment of glaucoma is reduced, with oxprenolone - the antihypertensive effect of the drug is reduced. Under the influence of octadin, it is possible to reduce the hyposecretory effect of atropine, which weakens the effect of M-cholinomimetics and anticholinesterase drugs. When used simultaneously with sulfonamide drugs, the risk of kidney damage increases; with drugs containing potassium, the formation of intestinal ulcers is possible; with nonsteroidal anti-inflammatory drugs, the risk of gastric ulcers and bleeding increases.

The effect of atropine sulfate can be enhanced by the simultaneous use of other drugs with an antimuscarinic effect (M-anticholinergics, antispasmodics, amantadine, some antihistamines, drugs from the butyrophenone group, phenothiazines, dispyramidives, quinidine, tricyclic antidepressants, non-selective monoamine reuptake inhibitors). Inhibition of peristalsis under the influence of atropine can lead to changes in the absorption of other drugs.

Features of application

Use with caution in patients with prostatic hypertrophy without urinary tract obstruction, with Down's disease, with cerebral palsy, reflux esophagitis, hiatal hernia combined with reflux esophagitis, nonspecific ulcerative colitis, megacolon, patients with xerostomia, elderly patients or weakened patients, with chronic lung diseases without reversible obstruction, with chronic lung diseases occurring with low production of thick sputum, which is difficult to separate, especially in young children and weakened patients, with autonomic (autonomic) neuropathy.

Use during pregnancy or breastfeeding

The drug is contraindicated during pregnancy.

The use of atropine sulfate during breastfeeding is contraindicated due to the risk of developing toxic effects on the child.

The ability to influence the reaction rate when driving vehicles or other mechanisms

Considering the possibility of adverse reactions such as dizziness, hallucinations, and accommodation disturbances, when using the drug you should refrain from driving vehicles or other mechanisms.

Directions for use and doses

Atropine sulfate is administered subcutaneously, intramuscularly, intravenously. During induction of anesthesia in order to reduce the risk of vagal suppression of the heart rate and reduce the secretion of the salivary and bronchial glands - 0.3-0.6 mg subcutaneously or 30-60 minutes before anesthesia in combination with morphine (10 mg morphine sulfate) - 1:00 before anesthesia. In case of poisoning with anticholinesterase drugs, atropine sulfate is administered 2 mg intramuscularly every 20-30 minutes until redness and dryness of the skin occurs, pupil dilation and tachycardia appear, and breathing normalizes. In case of moderate and severe poisoning, atropine can be administered for two days (until signs of “pereatropinization” appear).

For children, the highest single dose is:

• up to 6 months - 0.02 mg
• aged 6 months to 1 year - 0.05 mg
• aged 1 to 2 years - 0.2 mg
• at the age of 3 to 4 years - 0.25 mg
• aged 5 to 6 years - 0.3 mg
• aged 7 to 9 years - 0.4 mg
• aged 10 to 14 years - 0.5 mg.

Higher doses for adults subcutaneously: single - 1 mg, daily - 3 mg.

Adverse reactions

The side effects of the drug are mainly associated with the M-anticholinergic effect of atropine.

From the digestive system: dry mouth, thirst, impaired taste, dysphagia, decreased intestinal motility to atony, decreased tone of the biliary tract and gallbladder.

From the urinary system: difficulty and retention of urination.

From the cardiovascular system: tachycardia, arrhythmia, including extrasystole, myocardial ischemia, facial flushing, feeling of hot flashes.

From the nervous system: headache, dizziness, nervousness, insomnia.

From the side of the organ of vision: dilated pupils, photophobia, paralysis of accommodation, increased intraocular pressure, visual impairment.

From the respiratory system: a decrease in secretory activity and bronchial tone, which leads to the formation of viscous sputum, making it difficult to cough up.

From the skin: rash, urticaria, exfoliative dermatitis.

Manufacturer

LLC "Kharkov Pharmaceutical Enterprise" Health of the People ".