Gross formula

Pharmacological group of the substance Atropine

Nosological classification (ICD-10)

CAS code

Characteristics of the substance Atropine

Atropine sulfate is a white crystalline or granular powder, odorless. Easily soluble in water and ethanol, practically insoluble in chloroform and ether.

Pharmacology

Blocks m-cholinergic receptors. Causes mydriasis, paralysis of accommodation, increased intraocular pressure, tachycardia, xerostomia. Inhibits the secretion of bronchial and gastric, sweat glands. Relaxes the smooth muscles of the bronchi, gastrointestinal tract, bile and urinary systems - antispasmodic effect. Stimulates (large doses) the central nervous system. After intravenous administration, the maximum effect appears after 2-4 minutes, after oral administration (in the form of drops) after 30 minutes. In the blood, it is 18% bound to plasma proteins. Passes through the BBB. Excreted by the kidneys (50% unchanged).

Use of the substance Atropine

Peptic ulcer of the stomach and duodenum, pylorospasm, cholelithiasis, cholecystitis, acute pancreatitis, hypersalivation (parkinsonism, poisoning with heavy metal salts, during dental procedures), irritable bowel syndrome, intestinal colic, biliary colic, renal colic, symptomatic bradycardia (sinus, sinoatrial blockade, proximal AV blockade, electrical activity of the ventricles without pulse, asystole), for preoperative sedation; poisoning with m-cholinergic stimulants and anticholinesterase drugs (reversible and irreversible action), incl.

organophosphorus compounds; for X-ray studies of the gastrointestinal tract (if necessary to reduce the tone of the stomach and intestines), bronchial asthma, bronchitis with hyperproduction of mucus, bronchospasm, laryngospasm (prevention). To dilate the pupil and achieve paralysis of accommodation (determining the true refraction of the eye, examining the fundus), creating functional rest in inflammatory diseases and injuries of the eye (iritis, iridocyclitis, choroiditis, keratitis, thromboembolism and spasm of the central retinal artery).

Contraindications

Hypersensitivity, for ophthalmic forms - closed-angle glaucoma (including if it is suspected), open-angle glaucoma, keratoconus, children (1% solution - up to 7 years).

Restrictions on use

Diseases of cardio-vascular system in which an increase in heart rate may be undesirable: atrial fibrillation, tachycardia, chronic heart failure, coronary artery disease, mitral stenosis, arterial hypertension, acute bleeding; thyrotoxicosis (possibly increased tachycardia); increased body temperature (further increase is possible due to suppression of the activity of the sweat glands); reflux esophagitis, hiatal hernia, combined with reflux esophagitis (decreased motility of the esophagus and stomach and relaxation of the lower esophageal sphincter can slow down gastric emptying and increase gastroesophageal reflux through the sphincter with impaired function); gastrointestinal diseases accompanied by obstruction: achalasia of the esophagus, pyloric stenosis (possibly decreased motility and tone, leading to obstruction and delayed evacuation of gastric contents); intestinal atony in elderly or debilitated patients (possible development of obstruction), paralytic intestinal obstruction (possible development of obstruction); diseases with increased intraocular pressure: closed-angle (mydriatic effect, leading to an increase in intraocular pressure, can cause an acute attack) and open-angle glaucoma (mydriatic effect can cause a slight increase in intraocular pressure; adjustment of therapy may be required); nonspecific ulcerative colitis (high doses can inhibit intestinal motility, increasing the likelihood of paralytic ileus; in addition, the manifestation or exacerbation of such a severe complication as toxic megacolon is possible); dry mouth (long-term use may further increase the severity of xerostomia); liver failure (decreased metabolism) and kidney failure (risk of developing side effects due to decreased excretion); chronic lung diseases, especially in young children and weakened patients (a decrease in bronchial secretion can lead to thickening of secretions and the formation of plugs in the bronchi); myasthenia gravis (the condition may worsen due to inhibition of the action of acetylcholine); prostatic hypertrophy without urinary tract obstruction, urinary retention or predisposition to it, or diseases accompanied by urinary tract obstruction (including cervical Bladder due to prostatic hypertrophy); gestosis (possibly increased arterial hypertension); brain damage in children, cerebral palsy, Down's disease (response to anticholinergic drugs increases). For ophthalmological forms (additionally) - age over 40 years (risk of undiagnosed glaucoma), synechia of the iris.

Use during pregnancy and breastfeeding

Side effects of the substance Atropine

Systemic effects

From the outside nervous system and sense organs: headache, dizziness, insomnia, confusion, euphoria, hallucinations, mydriasis, paralysis of accommodation, impaired tactile perception.

From the cardiovascular system and blood (hematopoiesis, hemostasis): sinus tachycardia, worsening myocardial ischemia due to excessive tachycardia, ventricular tachycardia and ventricular fibrillation.

From the gastrointestinal tract: xerostomia, constipation.

Others: fever, intestinal and bladder atony, urinary retention, photophobia.

Local effects: transient tingling and increased intraocular pressure; with prolonged use - irritation, hyperemia of the skin of the eyelids; hyperemia and swelling of the conjunctiva, the development of conjunctivitis, mydriasis and paralysis of accommodation.

When administered in single doses<0,5 мг возможна парадоксальная реакция, связанная с активацией парасимпатического отдела вегетативной нервной системы (брадикардия, замедление AV проводимости).

Interaction

Weakens the effect of m-cholinomimetics and anticholinesterase drugs. Drugs with anticholinergic activity enhance the effect of atropine. When taken simultaneously with antacids containing Al 3+ or Ca 2+, the absorption of atropine from the gastrointestinal tract is reduced. Diphenhydramine and promethazine enhance the effect of atropine. The likelihood of developing systemic side effects is increased by tricyclic antidepressants, phenothiazines, amantadine, quinidine, antihistamines and other drugs with m-anticholinergic properties. Nitrates increase the likelihood of increased intraocular pressure. Atropine changes the absorption parameters of mexiletine and levodopa.

Routes of administration

Inside, intravenously, intramuscularly, PC, conjunctivally, subconjunctival or parabulbar, by electrophoresis. The ointment is placed behind the eyelids.

Precautions for the substance Atropine

For distal AV block (with wide QRS complexes), atropine is ineffective and is not recommended.

When instilling into the conjunctival sac, it is necessary to press the lower lacrimal opening to prevent the solution from entering the nasopharynx. With subconjunctival or parabulbar administration, it is advisable to prescribe validol to reduce tachycardia.

An intensely pigmented iris is more resistant to dilatation and to achieve an effect it may be necessary to increase the concentration or frequency of administration, so one should be wary of an overdose of mydriatics.

Pupil dilation can trigger an acute attack of glaucoma in people over 60 years of age and people with hyperopia, who are predisposed to glaucoma due to the fact that they have a shallow anterior chamber.

Atropine is a non-selective blocker of M-cholinergic receptors. The effect of the drug is the opposite of the effect that is observed when the parasympathetic division of the autonomic nervous system is excited.

Release form and composition

The active ingredient of the drug is a substance of the same name - atropine sulfate.

The drug is available in the following dosage forms:

• Eye drops 1%, 5 ml and 10 ml;
• Eye ointment 1%;
• Solution for injection 0.5 mg/ml 1 ml, 1 mg/ml 1 ml and 1 mg/ml 1.4 ml;
• Oral solution 1 mg/ml, 10 ml;
• Tablets 0.5 mg.

Indications for use

According to the instructions, Atropine is prescribed for the following diseases:

• Cholecystitis;
• Pylorospasm;
• Acute pancreatitis;
• Peptic ulcer of the stomach and duodenum;
• Cholelithiasis (cholelithiasis);
• Hypersalivation (increased secretion of the salivary glands);
• Irritable bowel syndrome;
• Renal, biliary and intestinal colic;
• Bronchospasm;
• Bronchitis with increased mucus production;
• Bronchial asthma;
• Laryngospasm (prevention);
• Symptomatic bradycardia;
• Poisoning with anticholinesterase drugs and M-cholinergic stimulants.

Atropine is widely used in ophthalmology. Eye drops are used to dilate the pupil, create functional rest in case of eye injuries and inflammatory diseases, as well as to achieve accommodation paralysis (when examining the fundus of the eye and determining the true refraction of the eye).

In addition, Atropine is used to medically prepare a patient for surgery.

Contraindications

For ophthalmic forms of Atropine, contraindications are open-angle and closed-angle glaucoma (including if it is suspected), keratoconus (thinning and change in the shape of the cornea), as well as childhood (1% solution is not prescribed to children under 7 years of age).

For other forms of the drug, the only contraindication is hypersensitivity to atropine sulfate or other components of the drug.

Directions for use and dosage

Atropine tablets are taken orally at 0.25-1 mg 1 to 3 times a day. Children under 18 years of age, depending on age, are prescribed 0.05-0.5 mg once or twice a day. The maximum single dose of the drug is 1 mg, and the daily dose is 3 mg.

The injection solution is administered subcutaneously, intravenously or intramuscularly 1-2 times during the day, 0.25-1 mg. To eliminate bradycardia, Atropine, according to the instructions, is prescribed intravenously at 0.5-1 mg for adults and 10 mcg/kg for children.

For preliminary medical preparation of the patient for surgery and general anesthesia, the drug is administered intramuscularly 45-60 minutes before the procedure: 400-600 mcg for adults and 10 mcg/kg for children.

When using Atropine in ophthalmology, the recommended dosage for adults is 1-2 drops of a 1% solution in the affected eye up to three times a day with an interval of 5-6 hours, depending on the indications. Children are prescribed a similar dose of the drug, but at a lower concentration.

Sometimes a 0.1% solution of Atropine is administered 0.2-0.5 ml subconjunctivally (under the mucous membrane of the eye) or 0.3-0.5 ml parabulbarly (injection under the eye). A 0.5% solution is injected from the anode through an eye bath or eyelids (by electrophoresis).

Side effects

When using Atropine, the following systemic (general) side effects are possible:

• Nervous system and sensory organs: dizziness, hallucinations, euphoria, insomnia, paralysis of accommodation, confusion, dilated pupils, impaired tactile perception;
• Cardiovascular and hematopoietic system: ventricular fibrillation, sinus tachycardia, ventricular tachycardia and worsening myocardial ischemia;
• Gastrointestinal tract: constipation, dry oral mucosa;
• Other reactions: urinary retention, fever, photophobia, lack of normal tone of the bladder and intestines.

Among the local effects when using Atropine, one can note an increase in intraocular pressure and transient tingling, and with prolonged use - hyperemia and irritation of the skin of the eyelids, redness and swelling of the conjunctiva, paralysis of accommodation, the development of conjunctivitis and mydriasis (pupil dilation).

With single doses (less than 0.5 mg), a paradoxical reaction may occur, which is associated with activation of the parasympathetic department (slowing of atrioventricular conduction, bradycardia).

special instructions

When instilling Atropine into the conjunctival sac, the lower lacrimal punctum should be pressed so that the solution does not enter the nasopharynx. To reduce tachycardia during parabulbar and subconjunctival administration of the drug, it is advisable to prescribe validol.

The intensely pigmented iris is more resistant to dilation, and to achieve the desired effect, an increase in the concentration of Atropine or the frequency of administration is required, so one should be wary of a possible overdose of drugs that dilate the pupil of the eye.

In patients with farsightedness and patients over 60 years of age who are predisposed to glaucoma, an acute attack of glaucoma may occur when using Atropine. This is due to the fact that their anterior chamber of the eye is shallow.

During the treatment period, you should refrain from driving vehicles and engaging in other potentially hazardous activities that require good vision, speed of psychomotor reactions and increased concentration.

Treatment with Atropine must be stopped gradually to avoid withdrawal syndrome.

Analogs

An analogue of the drug in composition is Atropine sulfate, and in terms of pharmacological action the following mydriatics are: Cyclomed, Midriacil and Irifrin.

Terms and conditions of storage

Atropine, according to the instructions, is stored in a place protected from light, out of reach of children. The room temperature should not exceed 25 °C. The shelf life of the medicine is 3 years.

Composition and release form of the drug

1 ml - ampoules (10) - cardboard boxes.
1 ml - ampoules (5) - contour plastic packaging (1) - cardboard packs.
1 ml - ampoules (5) - contour cell packaging (1) - cardboard packs.

pharmachologic effect

M-cholinergic receptor blocker is a natural tertiary amine. It is believed that atropine binds equally to the m 1 -, m 2 - and m 3 -subtypes of muscarinic receptors. Affects both central and peripheral m-cholinergic receptors.

Reduces the secretion of salivary, gastric, bronchial, and sweat glands. Reduces the tone of smooth muscles of internal organs (including bronchi, digestive system organs, urethra, bladder), reduces gastrointestinal motility. Has virtually no effect on the secretion of bile and pancreas. Causes mydriasis, paralysis of accommodation, reduces the secretion of tear fluid.

In average therapeutic doses, atropine has a moderate stimulating effect on the central nervous system and a delayed but long-lasting sedative effect. The central anticholinergic effect explains the ability of atropine to eliminate tremor in Parkinson's disease. In toxic doses, atropine causes agitation, agitation, hallucinations, and coma.

Atropine reduces the tone of the vagus nerve, which leads to an increase in heart rate (with a slight change in blood pressure) and an increase in conductivity in the His bundle.

In therapeutic doses, atropine does not have a significant effect on peripheral vessels, but with an overdose, vasodilation is observed.

When applied topically in ophthalmology, maximum pupil dilation occurs after 30-40 minutes and disappears after 7-10 days. Mydriasis caused by atropine is not eliminated by instillation of cholinomimetic drugs.

Pharmacokinetics

Well absorbed from the gastrointestinal tract or through the conjunctival membrane. After systemic administration, it is widely distributed in the body. Penetrates through the BBB. A significant concentration in the central nervous system is achieved within 0.5-1 hour. Protein binding is moderate.

T1/2 is 2 hours. Excreted in the urine; about 60% is unchanged, the remaining part is in the form of hydrolysis and conjugation products.

Indications

Systemic use: spasm of smooth muscle organs of the gastrointestinal tract, bile ducts, bronchi; peptic ulcer of the stomach and duodenum, acute pancreatitis, hypersalivation (parkinsonism, poisoning with heavy metal salts, during dental procedures), irritable bowel syndrome, intestinal colic, renal colic, bronchitis with hypersecretion, bronchospasm, laryngospasm (prevention); premedication before surgery; AV block, bradycardia; poisoning with m-cholinomimetics and anticholinesterase substances (reversible and irreversible effects); X-ray examination of the gastrointestinal tract (if necessary to reduce the tone of the stomach and intestines).

Local use in ophthalmology: for examining the fundus of the eye, for dilating the pupil and achieving accommodation paralysis in order to determine the true refraction of the eye; for the treatment of iritis, iridocyclitis, choroiditis, keratitis, embolism and spasm of the central retinal artery and some eye injuries.

Contraindications

Hypersensitivity to atropine.

Dosage

Orally - 300 mcg every 4-6 hours.

To eliminate bradycardia intravenously in adults - 0.5-1 mg; if necessary, the administration can be repeated after 5 minutes; children - 10 mcg/kg.

For the purpose of intramuscular premedication for adults - 400-600 mcg 45-60 minutes before anesthesia; children - 10 mcg/kg 45-60 minutes before anesthesia.

When applied topically in ophthalmology, 1-2 drops of a 1% solution are instilled (in children a solution of lower concentration is used) into the affected eye, the frequency of use is up to 3 times with an interval of 5-6 hours, depending on the indications. In some cases, a 0.1% solution is administered subconjunctivally 0.2-0.5 ml or parabulbar - 0.3-0.5 ml. Using electrophoresis, a 0.5% solution is injected from the anode through the eyelids or an eye bath.

Side effects

For systemic use: dry mouth, tachycardia, constipation, difficulty urinating, mydriasis, photophobia, paralysis of accommodation, dizziness, impaired tactile perception.

For local use in ophthalmology: hyperemia of the skin of the eyelids, hyperemia and swelling of the conjunctiva of the eyelids and eyeball, photophobia, dry mouth, tachycardia.

Drug interactions

When taken orally with drugs containing aluminum or calcium carbonate, the absorption of atropine from the gastrointestinal tract is reduced.

When used simultaneously with anticholinergic drugs and drugs with anticholinergic activity, the anticholinergic effect is enhanced.

When used simultaneously with atropine, it is possible to slow down the absorption of mexiletine, reduce the absorption of nitrofurantoin and its excretion by the kidneys. The therapeutic and side effects of nitrofurantoin are likely to increase.

When used simultaneously with phenylephrine, blood pressure may increase.

Under the influence of guanethidine, the hyposecretory effect of atropine may be reduced.

Nitrates increase the likelihood of increased intraocular pressure.

Procainamide enhances the anticholinergic effect of atropine.

Atropine reduces the concentration of levodopa in the blood plasma.

special instructions

Use with caution in patients with diseases of the cardiovascular system, in which an increase in heart rate may be undesirable: atrial fibrillation, tachycardia, chronic failure, coronary artery disease, mitral stenosis, arterial hypertension, acute bleeding; with thyrotoxicosis (possible increased tachycardia); at elevated temperatures (may further increase due to suppression of the activity of the sweat glands); with reflux esophagitis, hiatal hernia, combined with reflux esophagitis (decreased motility of the esophagus and stomach and relaxation of the lower esophageal sphincter can slow down gastric emptying and increase gastroesophageal reflux through the sphincter with impaired function); for gastrointestinal diseases accompanied by obstruction - achalasia of the esophagus, pyloric stenosis (possibly decreased motility and tone, leading to obstruction and retention of gastric contents), intestinal atony in elderly or debilitated patients (possible development of obstruction), paralytic ileus; with an increase in intraocular pressure - closed-angle (mydriatic effect, leading to an increase in intraocular pressure, can cause an acute attack) and open-angle glaucoma (mydriatic effect can cause a slight increase in intraocular pressure; adjustment of therapy may be required); with nonspecific ulcerative colitis (high doses can inhibit intestinal motility, increasing the likelihood of paralytic intestinal obstruction, in addition, the manifestation or exacerbation of such a severe complication as toxic megacolon is possible); with dry mouth (long-term use may cause further increase in the severity of xerostomia); with liver failure (decreased metabolism) and renal failure (risk of side effects due to decreased excretion); for chronic lung diseases, especially in young children and weakened patients (a decrease in bronchial secretion can lead to thickening of secretions and the formation of plugs in the bronchi); with myasthenia gravis (the condition may worsen due to inhibition of the action of acetylcholine); prostatic hypertrophy without urinary tract obstruction, urinary retention or predisposition to it, or diseases accompanied by urinary tract obstruction (including bladder neck due to prostatic hypertrophy); with gestosis (possibly increased arterial hypertension); brain damage in children, cerebral palsy, Down's disease (reaction to anticholinergic drugs increases).

The interval between doses of atropine and antacids containing aluminum or calcium carbonate should be at least 1 hour.

With subconjunctival or parabulbar administration of atropine, the patient must be given a tablet under the tongue to reduce tachycardia.

Impact on the ability to drive vehicles and machinery

During the treatment period, the patient must be careful when driving vehicles and engaging in other potentially hazardous activities that require increased concentration, speed of psychomotor reactions and good vision.

Pregnancy and lactation

Atropine penetrates the placental barrier. Adequate and strictly controlled clinical studies of the safety of atropine during pregnancy have not been conducted.

When administered intravenously during pregnancy or shortly before birth, tachycardia may develop in the fetus.

Atropine is found in breast milk in trace concentrations.

Use with caution in case of liver failure (decreased metabolism).

Use in old age

Use with caution in patients with diseases of the cardiovascular system, in which an increase in heart rate may be undesirable; with intestinal atony in elderly or debilitated patients (possible development of obstruction), with prostatic hypertrophy without urinary tract obstruction, urinary retention or predisposition to it, or diseases accompanied by urinary tract obstruction (including bladder neck due to prostatic hypertrophy glands).

Atropine is an antispasmodic and antichilinergic drug. Its active component is a poisonous alkaloid present in the leaves and seeds of plants of the nightshade family. The main principle of action of the drug is the ability to block the body's cholinergic systems located in the heart muscle and organs with smooth muscles.

Dosage form

The drug Atropine is produced by pharmaceutical companies in the form of a solution for injection and in the form of eye drops.

Description and composition

The active component, regardless of the dosage form, is atropine sulfate. Achieving the required dosage formula is ensured by an excipient – ​​saline solution.

The solutions are transparent in color; sedimentation is not allowed during storage. Turbidity in the composition may indicate improper storage of the medication.

Pharmacological group

The drug Atropine belongs to the group of antispasmodic and anticholinergic drugs. The active component of the medicinal composition is rapidly distributed in the patient’s body and removed from it by the liver and due to enzymatic hydrolysis. The binding rate to plasma proteins is about 18%. We should not forget about the substance’s ability to actively cross the placental barrier and penetrate into breast milk. The half-life of the drug is 2 hours. Half the dose of the drug is excreted from the patient’s body through the kidneys.

Indications for use

Atropine reduces the secretory function of the glands and promotes relaxation of smooth muscles. When using the composition in eye drop format, the pupil dilates and intraocular pressure increases. Paralysis of accommodation is ensured. After taking the drug, acceleration and stimulation of cardiac activity is ensured, this effect is achieved due to the ability of the composition to have a direct effect on the vagus nerve. The drug has a direct effect on the central nervous system and ensures activation of the respiratory center. When using toxic doses, increased motor and mental agitation is possible.

The list of indications for taking the drug can be presented as follows:

• ulcerative lesions of the stomach and duodenum;
• spasms of the bile ducts;
• spasms of the respiratory system;
• parkinsonism;
• poisoning with salts of heavy metals;
• bradycardia;
• renal colic;
• intestinal colic;
• irritable small bowel syndrome;
• bronchospasm;
• laryngospasm.

Atropine can be used during a number of X-ray studies of the gastrointestinal tract, before various surgical interventions in ophthalmology.

for adults

The drug Atropine can be used by patients in this category in the absence of contraindications to use. Elderly people often require dose adjustments to minimize the risk of complications during use. For liver and kidney damage, the composition is used with increased caution.

for children

The drug can be used in pediatric practice as prescribed by a specialist. In compliance with the rules of increased caution, the composition is prescribed to young children and persons with weakened immune systems. The drug may cause a decrease in the intensity of the processes of producing bronchial secretions, against this background the formation of plugs in the bronchi is possible. The composition is not used for serious brain damage or cerebral palsy.

Atropine can penetrate the placental barrier. Controlled studies of the use of the composition during pregnancy have not been conducted. The composition is not used during pregnancy for intravenous administration due to the possibility of developing tachycardia in the fetus. The active component of the drug can pass into breast milk in small quantities.

Contraindications

The composition is not prescribed to patients with hypersensitivity to the active substance.

Applications and dosages

The dosage regimen, frequency and duration of use are determined by the attending physician on an individual basis. Failure to comply with such recommendations may result in severe complications.

for adults

The recommended dose for adult patients is 300 mcg every 4-6 hours. In order to eliminate bradycardia, the composition is prescribed to adult patients at a dose of 0.5 - 1 mg. If necessary, the administration is repeated after 5 minutes. For premedication – 400-600 mcg once.

for children

To eliminate bradycardia in children, a dose of 10 mcg/kg of the patient’s body is used.

for pregnant women and during lactation

During pregnancy, the composition is used in doses recommended for adult patients as prescribed by a specialist.

Side effects

When taken systemically, the following reactions may occur:

• dry mouth;
• tachycardia;
• difficulty urinating;
• photophobia;
• dizziness;
• tactile perception disorders;
• paralysis of accommodation;
• mydriasis.

When using eye drops, side effects may include the following:

• swelling of the skin of the eyelids;
• hypermia;
• swelling of the conjunctiva;
• photophobia;
• tachycardia.

Interaction with other drugs

There are no data on the interaction of the drug with other medications. The possibility of sharing the composition with other drugs is determined on an individual basis.

special instructions

During the period of use of the drug Atropine, the patient must be careful when driving vehicles and while working with complex mechanisms.

Overdose

When used in doses regulated by the instructions, the likelihood of overdose is minimized. If the recommended doses are exceeded, a significant deterioration in the patient's well-being may occur. Sedatives can be used to eliminate adverse reactions that occur. If acute reactions occur, the patient should seek emergency medical help.

Storage conditions

The medicine is sold to the public through a network of pharmacies with a prescription. The composition should be stored at a temperature of no more than 25 degrees in a place protected from children. Eye drops should be stored in the refrigerator after opening the package.

Analogs

The drug Atropine has no structural analogues of the active substance. If it is impossible to use Atropine, your doctor will be able to select an adequate replacement.

Price

The cost of Atropine is on average 50 rubles. Prices range from 13 to 55 rubles.

The drug is available only with a prescription!

In case of overdose, the substance acts as a poison!

Pharmacological group: ;
Effect on receptors: muscarinic acetylcholine receptors types M1, M2, M3, M4 and M5
Systematic (IUPAC) name: (RS) - (8-methyl-8-azabicyclooct-3-yl)-3-hydroxy-2-phenylpropanoate
Trade names: Atropen
Legal status: Available by prescription only
Application: orally, intravenously, intramuscularly, rectally
Bioavailability: 25%
Metabolism: 50% hydrolyzed to tropical acid
Half-life: 2 hours
Excretion: 50% is excreted unchanged in urine
Formula: C 17 H 23 NO 3
Mol. weight: 289.369

Atropine is a naturally occurring tropane alkaloid extracted from (Atropa belladonna), (Datura stramonium), (Mandragora officinarum) and other plants of the family. Atropine is a secondary metabolite of these plants and serves as a drug with a wide range of effects. Atropine counteracts the activity of the glands called “rest and digest,” which is regulated by the parasympathetic nervous system. This is due to the fact that Atropine is a competitive antagonist of muscarinic acetylcholine receptors (acetylcholine is the main neurotransmitter used by the parasympathetic nervous system). Atropine causes dilation of the pupils, an increase in heart rate, and also reduces salivation and the activity of other secretions. Atropine is on the World Health Organization's list of essential medicines.

Description of action

Atropine is a natural tropane alkaloid, a racemic form of hyocyanine, found in plants of the nightshade family (Solanaceae). Atropine is a competitive, selective antagonist of postganglionic cholinergic receptors M1 and M2, inhibiting the action of acetylcholine. Its effect can be partially restored by using an AChE inhibitor. It affects muscarinic receptors of organs, blocking them in the following sequence: bronchi, heart, eyeballs, smooth muscles of the gastrointestinal tract and urinary tract; has the least effect on gastric secretion. The effect of atropine on the human body is multidirectional and, depending on the target organ, includes - respiratory tract: relaxation of smooth muscle, resulting in increased lumen of the bronchi, decreased mucus secretion; heart: causes an increase in heart rate and cardiac output, and also affects the sinoatrial node of the heart (to a lesser extent the atrioventricular node), accelerating nodal conduction and shortening the PQ interval. The effect of atropine on the heart is more pronounced in young people with high vagal tone; In the elderly, young children, black people, and in patients with diabetes mellitus and uremic neuropathy, atropine causes less clinical effects. Atropine affects the digestive tract: it causes a decrease in the tone of the smooth walls of the muscles of the gastrointestinal tract, weakens intestinal motility, reducing the secretion of gastric juice and accumulation of stomach contents, and has an antiemetic effect; urinary system: reduces the tone of the smooth muscles of the walls of the ureters and bladder; exocrine glands: reduces the secretion of tears, sweat, saliva, mucus and digestive enzymes; eyeball: mydriasis and paralysis of the ciliary muscle. Atropine has no effect on nicotinic receptors. Has a weak analgesic effect. Increases metabolism. Well absorbed when administered orally. When administered intravenously, it begins to act immediately, when inhaled - within 3–5 minutes, when administered intramuscularly - from several minutes to half an hour. After injection into the conjunctival sac, mydriasis occurs within 30 minutes and persists for 8-14 days, and paralysis of accommodation occurs after approximately 2 hours and continues for approximately 5 days. The half-life ranges from 3 hours (adults) to 10 hours (children and elderly people). Atropine binds 25-50% to plasma proteins, penetrates into the cerebral circulation, through the placenta and into breast milk. 30-50% of the drug is excreted unchanged by the kidneys, 50% in the form of inactive metabolites through the liver; the rest is subjected to enzymatic destruction.

Name

Belladonna got its name (bella donna, which translates from Italian as “beautiful woman”) due to the fact that in the past it was used to dilate the pupils of the eyes, which was considered a beautiful cosmetic effect. The name Atropine and the name of the belladonna genus come from the name of Atropa, one of the three moiras, goddesses of fate, who, according to Greek mythology, were able to choose the manner of death of a person.

Medical use

Atropine is a competitive antagonist of muscarinic acetylcholine receptors types M1, M2, M3, M4 and M5. It is classified as an anticholinergic drug. Acting as a non-selective muscarinic acetylcholinergic antagonist, atropine increases sinus node output and conduction through the atrioventricular node (AV) of the heart by antagonizing the vagus nerve, blocking acetylcholine receptor sites, and decreasing bronchial secretions.

Ophthalmic use

Atropine is used topically as a cycloplegic to temporarily paralyze the reflex of accommodation, and as a mydriatic to dilate the pupils. Atropine is slowly degraded, typically within 7 to 14 days, so it is typically used as a therapeutic mydriatic, whereas a (shorter-acting cholinergic antagonist) or (α-adrenergic agonist) is more preferably used for ophthalmic examinations. Atropine causes pupil dilation by blocking the contraction of the circular pupillary sphincter, which is normally stimulated by the release of acetylcholine, promoting contraction of the radial muscle, which contracts and dilates the pupil. Atropine causes cycloplegia by paralyzing the ciliary muscles, the action of which inhibits accommodation, which ensures accurate refraction in children and relieves pain associated with iridocyclitis. Atropine may be used to treat glaucoma caused by ciliary body block (malignant glaucoma). Atropine is contraindicated in patients predisposed to glaucoma. Atropine can be prescribed to patients with eyeball injuries.

Reanimation

Injectable Atropine is used to treat bradycardia (extremely low heart rate). Atropine blocks the action of the vagus nerve, part of the heart's parasympathetic system, whose main action is to reduce heart rate. Thus, its main function in this vein is to increase heart rate. Atropine was included in international resuscitation guidelines for use in cardiac arrest associated with asystole and electromechanical dissociation, but was removed in 2010 due to lack of evidence. For the treatment of symptomatic bradycardia, the usual dose of the drug is 0.5 to 1 mg intravenously, which can be repeated every 3 to 5 minutes until a total dose of 3 mg is reached (maximum 0.04 mg/kg). Atropine is also used to treat second-degree heart block type 1 Mobitz (Wenckebach block), as well as to treat third-degree heart block with a high Purkinje rhythm or branch atrioventricular node rhythm. The drug is generally not effective for the treatment of second-degree heart block of the Mobitz type 2, and for the treatment of third-degree heart block with low Purkinje rhythm or ventricular premature beats. One of the main actions of the parasympathetic nervous system is to stimulate the M2 muscarinic receptor in the heart, however Atropine inhibits this action.

Secretions and bronchospasms

The action of Atropine on the parasympathetic nervous system inhibits the salivary and mucous glands. The drug may also inhibit sweating through the sympathetic nervous system. It may be used in the treatment of hyperhidrosis, and may prevent death rattle in dying patients. Although Atropine has not been officially approved for any of these uses, it has been actively used for these purposes in medical practice.

Treatment of organophosphate poisoning

Atropine is not a viable antidote for organophosphorus poisoning. However, because Atropine blocks the action of acetylcholine at muscarinic receptors, it is also used to treat poisoning from organophosphate insecticides and nerve gases such as tabun (GA), sarin (GB), soman (GD), and VX. Combatants at risk of chemical poisoning often inject Atropine and Obidoxime into the thigh muscles. Atropine is often used in combination with pralidoxime chloride. Atropine is used as a therapy to treat symptoms of SLUDGE syndrome (salivation, lacrimation, urination, sweating, increased gastrointestinal motility, vomiting) caused by organophosphate poisoning, or DUMBBELSS (diarrhea, urination, miosis, bradycardia, bronchospasm, agitation, lacrimation, drooling and sweating). Some of the nerve agents attack and destroy acetylcholinesterase by phosphorylation, increasing the effects of acetylcholine. Pralidoxime (2-PAM) is used for organophosphorus poisoning because it is able to break down this phosphorylation. Atropine can be used to reduce the effects of toxicity because it blocks muscarinic acetylcholine receptors, which are otherwise overstimulated by excessive accumulation of acetylcholine.

Optical penalization

In refractive and accommodative amblyopia, if the occlusion method is not suitable, Atropine is sometimes used to cause blur in the healthy eye.

Side effects of Atropine and overdose

Adverse reactions to Atropine include ventricular fibrillation, supraventricular or ventricular tachycardia, dizziness, nausea, blurred vision, loss of balance, dilated pupils, photophobia, dry mouth and potentially extreme agitation, dissociative hallucinations and agitation, especially among the elderly. These latter effects are due to the fact that Atropine is able to cross the blood-brain barrier. Due to the hallucinogenic properties of Atropine, some people have used the drug recreationally, although such experiences are potentially dangerous and often unpleasant. In case of overdose, Atropine acts as a poison. Atropine is sometimes combined with potentially addictive drugs, particularly opioid anti-diarrhea drugs such as diphenoxylate or difenoxin, in which case the secretion-reducing effects of Atropine may also be used to combat symptoms of diarrhea. Although Atropine is used in emergency situations to treat bradycardia (slow heart rate), when administered in very low doses it can lead to a paradoxical slowing of heart rate, apparently as a result of a central effect on the central nervous system. Atropine has no effect in doses of 10 to 20 mg per person. The semi-lethal dose of the drug is 453 mg per person (oral). The antidote to Atropine is or. A well-known mnemonic used to describe the physiological manifestations of an overdose of Atropine is as follows: “hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter.” a mouse, dry as a bone, red as a beet, and crazy as a hatter"). These associations reflect specific changes in warmth, dry skin with decreased sweating, blurred vision, decreased sweating/lacrimation, dilation of blood vessels, and effects on muscarinic receptors type 4 and 5 in the central nervous system. These symptoms are known as anticholinergic toxidrome, and can also be caused by the use of other drugs with anticholinergic effects, such as and antipsychotic drug.

Chemistry and pharmacology

Atropine is a racemic mixture of d-hyoscyamine and l-hyoscyamine, with most of its physiological effects associated with l-hyoscyamine. Its pharmacological effects are due to binding to muscarinic acetylcholine receptors. Atropine is an antimuscarinic drug. Significant levels of atropine in the central nervous system are achieved within 30 minutes - 1 hour. Atropine is rapidly eliminated from the blood with a half-life of about 2 hours. About 60% of the drug is excreted unchanged in the urine, most of the remainder is contained in the urine as products of hydrolysis and conjugation. The effect of the drug on the iris and ciliary muscle can last for more than 72 hours. The most common Atropine compound used in medicine is Atropine sulfate (monohydrate) (C17H23NO3) 2 H2O H2SO4, full chemical name 1α H, 5α H-tropan-3-ol α (±)-tropate (ester), sulfate monohydrate. The vagus (parasympathetic) nerves innervate acetylcholine (ACh), released into the heart as the main transmitter. ACh binds to muscarinic receptors (M2), which are found mainly on cells containing the sinus and atrioventricular nodes. Muscarinic receptors are coupled to the Gi protein, so vagal activation reduces cAMP. Activation of Gi protein also leads to activation of Kach channels, which increase potassium efflux and hyperpolarize cells. An increase in the activity of the vagus nerve in relation to the SA node reduces the pulsation frequency of sinus cells, reducing the pacemaker potential coefficient (phase 4 of the action potential); this decreases the heart rate (negative chronotropy). The change in phase 4 coefficient occurs as a result of changes in potassium and α currents, as well as the slowly incoming sodium current responsible for sinus flow (If). By hyperpolarizing the cell, activation of the vagus nerve increases the threshold of the cell's pulsating frequency, which helps to reduce the pulsating frequency. Similar electrophysiological effects occur at the AV node, however, in this tissue these changes manifest themselves as a decrease in the speed of impulse conduction through the AV node (negative dromotropy). At rest, there is a greater degree of vagal tone on the heart, which is responsible for the decrease in resting heart rate. There is also some innervation of the vagus nerve to the ciliated muscle, and to a much lesser extent, to the ventricular muscle. Activation of the vagus nerve results in a slight decrease in atrial contraction (inotropy) and even a decrease in ventricular contraction. Muscarinic receptor antagonists bind to muscarinic receptors, thereby preventing ACh from binding to the receptor and activating it. By blocking the action of ACh, muscarinic receptor antagonists are very effective in blocking the action of the vagus nerve on the heart. Thus, they increase heart rate and conduction velocity.

Story

In the fourth century BC, Theophrastus described mandrake as a remedy for wounds, gout and insomnia, and as a “love potion.” By the first century AD, Dioscorides described mandrake wine as an anesthetic to treat pain or insomnia, to be given before surgery or cauterization. Throughout the Roman and Islamic empires, nightshades, which contain tropane alkaloids, were used for anesthesia, often in combination with opium. This use continued in Europe until these substances replaced ether, chloroform and other modern anesthetics. Cleopatra in the last century BC. used Atropine extracts from Egyptian henbane to dilate pupils, as large pupils were considered very attractive. During the Renaissance, women used the juice of belladonna berries to enlarge the pupils of their eyes for cosmetic purposes. In the late nineteenth and early twentieth centuries, the practice was briefly revived in Paris. The mydriatic effects of Atropine were studied, in particular, by the German chemist Friedlieb Ferdinand Runge (1795-1867). In 1831, German pharmacist Heinrich F. G. Main (1799-1864) developed Atropine in pure crystalline form. The substance was first synthesized by the German chemist Richard Willstetter in 1901.

Natural Sources of Atropine

Atropine is found in many plants of the nightshade family. Common sources include Atropa belladonna, Datura inoxia, D. metel, and D. stramonium. Other sources include plants from the genera Brugmansia and Hyoscyamus. The genus Nicotiana (which includes the tobacco plant, N. tabacum) is also a member of the nightshade family, but these plants do not contain atropine or other tropane alkaloids.

Synthesis

Atropine can be synthesized by reacting tropine with tropical acid in the presence of hydrochloric acid.

Biosynthesis

The biosynthesis of Atropine begins with, undergoing transamination to form phenylpyruvic acid, which is then reduced to phenyllactic acid. Coenzyme A then combines with phenyllactic acid with tropine to form littorin, which then undergoes a radical rearrangement initiated by the P450 enzyme to form hyoscyamine aldehyde. Dehydrogenase then reduces the aldehyde into a solution of the primary alcohol (-)-hyoscamine, after racemization of which Atropine is formed.