Atropine sulfate

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ATROPINE SULFATE

Composition:

Active substance: atropine;

1 ml of solution contains 1 mg of atropine sulfate;

Excipients: 0.1 M hydrochloric acid, water for injections.

Pharmaceutical form. Injection solution.

Main physico-chemical properties: clear, colorless liquid.

Pharmacotherapeutic group. Drugs for the treatment of functional gastrointestinal disorders. Belladonna alkaloids, tertiary amines. ATC code A03BA01.

Pharmacological Properties.

Pharmacodynamics.

The mechanism of action is due to atropine's selective blockade of M-cholinergic receptors (with lesser effect on N-cholinergic receptors), rendering them insensitive to acetylcholine produced at the endings of postganglionic parasympathetic neurons. Atropine's ability to bind to cholinergic receptors is explained by the presence in its molecule of a fragment that confers affinity for the endogenous ligand—acetylcholine. Atropine sulfate reduces secretion of salivary, bronchial, gastric, and sweat glands, increases the viscosity of bronchial secretions, suppresses the activity of cilia in the bronchial ciliated epithelium, thereby reducing mucociliary transport, accelerates heart rate, increases AV-conductivity, reduces the tone of smooth-muscle organs, decreases the volume and total acidity of gastric juice (especially when cholinergic regulation of secretion predominates), reduces basal and nocturnal gastric secretion, and to a lesser extent decreases stimulated secretion. It produces marked mydriasis (during which intraocular pressure may increase). By penetrating the blood-brain barrier (BBB), atropine exerts a stimulatory effect on the respiratory center at therapeutic doses.

Pharmacokinetics.

After intravenous administration, the maximum effect occurs within 2–4 minutes. Atropine sulfate is rapidly absorbed into the bloodstream from the site of administration. It is rapidly distributed throughout the body and penetrates the blood-brain barrier, placental barrier, and into breast milk. In the blood, atropine is approximately 50% protein-bound; its volume of distribution is about 3 L/kg. After intravenous administration, plasma concentration of atropine decreases in two phases. The first phase—rapid—has a half-life of approximately 2 hours. During this phase, about 80% of the administered dose is excreted in urine. During the second phase, the remaining portion of the drug is excreted in urine with a half-life of 13–36 hours. Atropine is metabolized in the liver via enzymatic hydrolysis; approximately 50% of the dose is excreted unchanged by the kidneys.

Clinical characteristics.

Indications. As a symptomatic agent in pylorospasm, acute pancreatitis, cholelithiasis, urinary tract spasms, bronchial asthma, bradycardia, and as a consequence – increased vagus nerve tone; to reduce secretion of salivary, gastric, bronchial, and sometimes sweat glands; for radiological examination of the gastrointestinal tract (to reduce organ tone and motor activity).

The drug may also be used before anesthesia and surgery, and during surgical procedures, as an agent preventing broncho- and laryngospasms, reducing glandular secretions, reflex responses, and adverse effects caused by vagus nerve stimulation. As a specific antidote in poisoning with cholinomimetic compounds and anticholinesterase agents (including organophosphorus compounds).

Contraindications. Hypersensitivity to the components of the drug. Cardiovascular diseases in which an increase in heart rate may be undesirable: atrial fibrillation, tachycardia, chronic heart failure, ischemic heart disease, mitral stenosis, severe arterial hypertension; acute bleeding; thyrotoxicosis; hyperthermic syndrome; gastrointestinal disorders accompanied by obstruction (esophageal achalasia, pyloric stenosis, intestinal atony); glaucoma; hepatic and renal insufficiency; myasthenia gravis; urinary retention or predisposition to it; central nervous system lesions.

Interaction with other medicinal products and other forms of interaction.

When atropine sulfate is used with monoamine oxidase inhibitors, cardiac arrhythmias may occur; with quinidine and procainamide – summation of cholinolytic effects is observed. When taken orally together with convallaria preparations or tannins, physicochemical interactions occur, leading to mutual weakening of effects.

Atropine sulfate reduces the duration and depth of action of narcotic agents and diminishes the analgesic effect of opioids.

Concomitant use with diphenhydramine or diprazine enhances the effect of atropine; with nitrates, haloperidol, and systemic corticosteroids – increases the likelihood of elevated intraocular pressure; with sertraline – the depressive effect of both drugs is enhanced; with spironolactone and minoxidil – the effect of spironolactone and minoxidil is reduced; with penicillins – the effect of both drugs is enhanced; with nizatidine – the action of nizatidine is enhanced; with ketoconazole – absorption of ketoconazole is reduced; with ascorbic acid and attapulgite – the effect of atropine is diminished; with pilocarpine – the effect of pilocarpine in glaucoma treatment is reduced; with oxprenolol – the antihypertensive effect of the drug is diminished. Under the influence of octadine, a possible reduction in the hyposecretory effect of atropine may occur; atropine also antagonizes the action of M-cholinomimetics and anticholinesterase agents.

Concomitant use with sulfonamide drugs increases the risk of kidney damage; with potassium-containing preparations – intestinal ulceration may occur; with nonsteroidal anti-inflammatory drugs – increased risk of gastric ulcers and bleeding.

The action of atropine sulfate may be enhanced when used concomitantly with other drugs having antimuscarinic effects (M-cholinoblockers, spasmolytics, amantadine, certain antihistamines, butyrophenones, phenothiazines, disopyramides, quinidine, tricyclic antidepressants, nonselective inhibitors of neuronal monoamine reuptake). Atropine-induced inhibition of peristalsis may lead to altered absorption of other medicinal products.

Special precautions for use.

Use with caution in patients with hypertrophy of the prostate without urinary tract obstruction, Down's syndrome, cerebral palsy in children, reflux esophagitis, hiatal hernia associated with reflux esophagitis, ulcerative colitis, megacolon, patients with xerostomia, elderly patients or debilitated patients, chronic lung diseases without reversible obstruction, chronic lung diseases accompanied by low production of thick, difficult-to-expectorate sputum, especially in young children and debilitated patients; in patients with vegetative (autonomic) neuropathy.

Use during pregnancy or breastfeeding. The drug is contraindicated during pregnancy.

Atropine sulfate is contraindicated during breastfeeding due to the risk of developing toxic effects in the infant.

Ability to influence reaction speed when driving or operating machinery. Due to the possible occurrence of adverse reactions such as dizziness, hallucinations, and accommodation disorders, patients should refrain from driving or operating machinery while taking this medication.

Administration and Dosage

Atropine sulfate is administered subcutaneously, intramuscularly, or intravenously.
For pre-anesthetic medication to reduce the risk of vagus-mediated bradycardia and to decrease secretions of salivary and bronchial glands: 0.3–0.6 mg subcutaneously or intramuscularly 30–60 minutes before anesthesia; when combined with morphine (10 mg morphine sulfate) – 1 hour before anesthesia.
In cases of poisoning with anticholinesterase agents, administer atropine sulfate 2 mg intramuscularly every 20–30 minutes until signs of atropinization appear: skin flushing and dryness, pupil dilation, tachycardia, and normalization of respiration. In moderate to severe poisoning, atropine may be administered for up to 2 days (until signs of "over-atropinization" appear).

Maximum single doses for children by age:

• Under 6 months of age – 0.02 mg;
• From 6 months to 1 year – 0.05 mg;
• From 1 to 2 years – 0.2 mg;
• From 3 to 4 years – 0.25 mg;
• From 5 to 6 years – 0.3 mg;
• From 7 to 9 years – 0.4 mg;
• From 10 to 14 years – 0.5 mg.

Maximum doses for adults (subcutaneous): single dose – 1 mg; daily dose – 3 mg.

Atropine sulfate should be administered with caution to elderly patients.

Children. Infants in the first three months of life are particularly sensitive to atropine.

Administer the drug to children in doses specified in the section "Administration and Dosage".

Overdose

Symptoms:
In mild overdose: dry mouth, pupil dilation, accommodation disturbances, tachycardia, difficulty in urination, intestinal atony, dizziness, impaired heat dissipation, reduced sweating.

In poisoning: pupil dilation, increased intraocular pressure, dry mucous membranes and skin, elevated body temperature, urinary retention, tachycardia, headache, dizziness, hallucinations, complete disorientation, sudden psychomotor agitation; seizures with loss of consciousness, decreased arterial pressure, and coma may occur.

Treatment:
Administration of antidotes – proserin (1 ml of 0.05% solution subcutaneously) or physostigmine (0.5–1 ml of 0.1% solution subcutaneously).
For psychomotor agitation – aminazine (chlorpromazine), 2 ml of 2.5% solution intramuscularly.
For seizures – barbiturates (5–10 ml of 2.5% sodium thiopental solution intravenously, or up to 10–15 ml of 2.5% hexenal solution intravenously, administered in 3–4 ml portions with 30-second intervals).
For sudden, pronounced hyperthermia – apply ice to the head and groin area, use wet wraps.
For tachycardia – inderal (propranolol).
For urinary retention – catheterization.
In severe intoxication – forced diuresis, blood alkalinization. Intravenous infusions of glucose with ascorbic acid are indicated.

Side effects.

The adverse effects of the drug are mainly related to the M-cholinolytic action of atropine.

Gastrointestinal tract: dry mouth, thirst, taste disturbances, dysphagia, decreased intestinal motility up to atony, reduced tone of bile ducts and gallbladder.

Urinary system: difficulty and retention of urination.

Cardiovascular system: tachycardia, arrhythmia including extrasystoles, myocardial ischemia, facial flushing, sensation of hot flushes.

Nervous system: headache, dizziness, nervousness, insomnia.

Eyes: mydriasis, photophobia, accommodation paralysis, increased intraocular pressure, visual disturbances.

Respiratory system: decreased secretory activity and bronchial tone, leading to formation of viscous sputum that is difficult to cough up.

Skin: skin rashes, urticaria, exfoliative dermatitis.

Immune system: anaphylactic reactions, anaphylactic shock.

Other: decreased sweating, dry skin, dysarthria, injection site reactions, hypersensitivity reactions.

Shelf life. 5 years.

Storage conditions. Store at a temperature not exceeding 25 °C in the original packaging.

Keep out of reach of children.

Incompatibility. Should not be mixed with other medicinal products.

Packaging. 1 ml in ampoules, 10 in a pack; 10, 5x2 in blisters in a pack.

Prescription status. Prescription only.

Manufacturer.

Limited Liability Company "Experimental Plant "GNCLS".

LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVTYA".

Manufacturer's address and place of business.

Ukraine, 61057, Kharkiv region, city of Kharkiv, Vorobiova Street, building 8.

(Limited Liability Company "Experimental Plant "GNCLS")

Ukraine, 61013, Kharkiv region, city of Kharkiv, Shevchenka Street, building 22.

(LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVTYA")