Description
Pharmacological action
Pharmacodynamics. Ipratropium bromide is a bronchodilating agent that blocks m-cholinergic receptors of the smooth muscles of the tracheobronchial tree and suppresses reflex narrowing of the bronchi (bronchoconstriction). Having structural similarities with the acetylcholine molecule, it is a competitive antagonist. Anticholinergics (m-anticholinergics) prevent an increase in the intracellular concentration of calcium ions, which occurs due to the interaction of acetylcholine with muscarinic receptors located in the smooth muscles of the bronchi. Calcium ions are released via secondary intermediaries (mediators), which include ITF (inositol triphosphate) and DAG (diacyglycerol).
Ipratropium bromide effectively prevents the narrowing of the bronchi resulting from the inhalation of cigarette smoke, cold air, the action of various bronchospasm agents, and also inhibits bronchospasm associated with the influence of the vagus nerve. When inhaled, it practically does not have a resorptive effect. Bronchodilation following inhalation of ipratropium bromide is mainly a consequence of local and specific effects of the drug on the lungs, and not the result of its systemic effect.
After taking ipratropium bromide in patients with bronchospasm due to chronic obstructive pulmonary disease, a significant improvement in lung function is observed within 15 minutes, reaching a maximum after 1-2 hours and lasting up to 4-6 hours.
Pharmacokinetics. Suction. After inhalation, 10-30% of the administered dose of ipratropium bromide usually enters the lungs (depending on the dosage form and method of inhalation). Most of the dose is swallowed and enters the gastrointestinal tract.
Part of the dose of ipratropium bromide entering the lungs quickly reaches the systemic circulation (within a few minutes).
General systemic bioavailability of ipratropium bromide, administered orally and inhaled,responsibly, based on the data that the total renal excretion (within 24 hours) of the starting compound is approximately 46% of the value of the intravenous dose, less than 1% of the dose used orally and about 3-13% of the inhaled dose of ipratropium bromide.
Distribution
The kinetic parameters describing the distribution of ipratropium bromide were calculated based on its plasma concentrations after intravenous administration. A rapid two-phase decrease in the concentration of ipratropium bromide in the blood plasma is observed. The apparent volume of distribution during the state of equilibrium concentration (Css) is approximately 176 L ( 2.4 L / kg).
Ipratropium bromide binds to blood plasma proteins (albumin and -1 acid glycoprotein) to a minimum extent (less than 20%).
ipratropium bromide, being a quaternary amine, it does not cross the blood-brain barrier.
Metabolism. After intravenous administration of ipratropium bromide, approximately 60% of the dose is metabolized by oxidation, mainly in the liver and partially excreted in the urine. The main metabolites excreted in the urine bind weakly to muscarinic receptors and are considered inactive. After inhalation of ipratropium bromide, about 77% of the systemic available dose is metabolized by hydrolysis of the ester bond (41%) and conjugation (36%).
Excretion
The elimination half-life (T1 / 2) during the terminal phase is approximately 1.6 hours. The total clearance of ipratropium bromide is 2.3 l / min, and the renal clearance is 0.9 l / min.
The total renal excretion within 6 days of the isotope-labeled dose including the parent compound and all metabolites is 72.1% after intravenous administration, 9.3% after oral administration, and 3.2% after inhalation. Excretion through the intestine of an isotope-labeled dose is 6.3% after intravenous administration, after ingestion – 88.5%, and after inhalation use – 69.4%.
The elimination half-life (T1 / 2) of the parent compound and metabolites with intravenous administration is about 2 ² 3 hours.
Indications
Chronic obstructive pulmonary disease (including chronic obstructive bronchitis, pulmonary emphysema).
Bronchial asthma (mild to moderate).
Emphysema of the lungs.
Contraindications
– hypersensitivity to atropine and its derivatives
– hypersensitivity to ipratropium bromide or to other components of the
preparation – age under 18 years.
With caution, Ipratropium-native should be prescribed with caution in patients with diseases such as angle-closure glaucoma, urinary tract obstruction, prostatic hyperplasia, and cystic fibrosis.
Composition
Active ingredient: 0.261 mg ipratropium bromide monohydrate in terms of ipratropium bromide 0.25 mg.
Excipients: sodium benzoate, disodium edetate dihydrate (corresponds to disodium edetate), citric acid monohydrate (corresponds to anhydrous citric acid), sodium hydroxide to a pH of 3.4 ± 0.1, water for injection.
Side effects of
Many of these adverse reactions may be due to the anticholinergic properties of ipratropium bromide.
The drug Ipratropium-native, like any inhalation therapy, can cause local irritation. The most common adverse reactions reported in clinical trials were headache, pharyngeal irritation, coughing, dry mouth, gastrointestinal motility (including constipation, diarrhea, and vomiting), nausea, and dizziness.
Adverse reactions are distributed according to frequency of occurrence. The following criteria were used to evaluate the frequency: very often (> 1/10) often (from 1/100 to 1/10) infrequently (from 1/1000 to 1/100) rarely (from 1/10000 to 1/1000) very rarely (<1/10000), (including individual messages ) frequency is unknown. Infectious and parasitic diseases: often – flu-like symptoms, infections of the upper respiratory tract infrequently – urinary tract infections. Disorders from the immune system: infrequently – hypersensitivity, anaphylactic reactions, angioedema (Quincke’s edema). Disorders of the nervous system: often – headache, dizziness. Disorders of the organ of vision: infrequently – blurred vision, mydriasis, increased intraocular pressure, glaucoma, acute pain in the eyes, the appearance of a halo around objects, conjunctival hyperemia, corneal edema rarely – disturbance of accommodation. Disorders of the heart: infrequently – palpitations, supraventricular (supraventricular) tachycardia rarely – atrial fibrillation, increased heart rate. Vascular disorders: frequency unknown – lowering blood pressure (hypotension). Disorders of the respiratory system, chest and mediastinal organs: often – pharyngeal irritation, cough, shortness of breath infrequently – bronchospasm, paradoxical bronchospasm, laryngospasm, pharyngeal edema, dry throat, sinusitis. Disorders of the gastrointestinal tract: often dry mouth, nausea, impaired motility of the gastrointestinal tract infrequently – diarrhea, constipation, vomiting, dyspepsia, change in taste, stomatitis. Disorders of the skin and subcutaneous tissue: infrequently – rash, itching rarely – urticaria. Disorders of the kidneys and urinary tract: infrequently – urinary retention. If any of the adverse reactions indicated in the instructions are aggravated or you notice any other adverse reactions not listed in the instructions, inform your doctor. Drug interaction With the simultaneous use of 2-adrenergic agonists and xanthine derivatives potentiate the bronchodilating effect of the drug. Anticholinergic effect is enhanced by antiparkinsonian drugs, quinidine, tricyclic antidepressants. With simultaneous use with other anticholinergics, an additive effect is noted. Patients with angle-closure glaucoma should use ipratropium-native with inhaled 2-adrenergic agonists with extreme caution, since the risk of developing an acute glaucoma attack increases. Ipratropium native, a solution for inhalation should not be prescribed simultaneously with an inhaled solution of cromoglicic acid, given the possibility of precipitation (precipitation). Overdose Symptoms: No specific symptoms of overdose. Given the breadth of the therapeutic effect and the local method of using the drug Ipratropium-native, the appearance of any serious anticholinergic symptoms is unlikely. Minor manifestations of systemic anticholinergic effects are possible, such as dry mouth, accommodation disturbances, and an increase in heart rate. Treatment: symptomatic treatment. Storage conditions In the dark place at a temperature of no higher than 25 ° C. Do not freeze. Keep out of the reach of children. Shelf life 3 years. D active substance ipratropium bromide Terms and conditions prescription lekarstvennaja form Solution for ynhalyatsyy Prescription Adults prescribed by a doctor, Children according to doctor’s prescription Indications Bronchitis, bronchospasm, Bronhialynaya asthma Vospalenie legkih, Nizkaya obuchaemosty Nativ, Russia
