Ipratropium bromide mechanism of action
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Mechanism of Action of Ipratropium Bromide
Anticholinergic Pathway and Bronchodilation
Ipratropium bromide, also known as Sch 1000, is a bronchodilator that functions primarily through an anticholinergic mechanism. This drug inhibits the action of acetylcholine on muscarinic receptors in the bronchial smooth muscle, leading to bronchodilation. By blocking these receptors, ipratropium bromide prevents the increase in cyclic guanosine monophosphate (cGMP), which is associated with bronchoconstriction1 4.
Efficacy in Asthma and Chronic Bronchitis
Ipratropium bromide has been shown to be effective in treating both asthma and chronic bronchitis. In patients with asthma, it provides a longer duration of bronchodilation compared to beta-agonists like isoproterenol, making it a valuable addition to asthma management1. For chronic bronchitis, ipratropium bromide demonstrates prolonged efficacy, particularly at higher doses, without significant cardiovascular side effects1.
Role in Acute Asthma Exacerbations
In emergency settings, ipratropium bromide is often used as an adjunctive therapy with beta2-agonists for acute asthma exacerbations. Studies have shown that this combination improves lung function and reduces hospitalization rates in both adults and children3. The additive effect of ipratropium and beta2-agonists enhances bronchodilation and provides better clinical outcomes during acute asthma attacks3.
Impact on Respiratory Function in Mechanically Ventilated Patients
In mechanically ventilated patients with acute airflow obstruction, ipratropium bromide has been found to reduce inspiratory resistance and improve respiratory symptoms. This effect is attributed to its action on the large airways, leading to better airflow and symptom relief without significant changes in arterial oxygen or carbon dioxide levels4.
Pulmonary Absorption and Transport Mechanism
Ipratropium bromide is primarily absorbed in the lungs when administered via inhalation. The drug's uptake in bronchial epithelial cells is mediated by organic cation/carnitine transporters, specifically OCTN1 and OCTN2. These transporters facilitate the drug's absorption, ensuring its pharmacological activity in the respiratory tract5.
Cardiovascular Considerations
While ipratropium bromide is effective in managing obstructive pulmonary diseases, it has been associated with an increased risk of cardiovascular events in patients with underlying ischemic heart disease. Studies in nonclinical models have shown that ipratropium can exacerbate myocardial injury during ischemia/reperfusion, highlighting the need for caution in patients with cardiovascular conditions2.
Conclusion
Ipratropium bromide is a potent anticholinergic bronchodilator that effectively manages asthma and chronic bronchitis by inhibiting muscarinic receptors and reducing cGMP levels. Its use in acute asthma exacerbations, particularly in combination with beta2-agonists, provides significant clinical benefits. However, its potential cardiovascular risks necessitate careful consideration in patients with pre-existing heart conditions. Overall, ipratropium bromide remains a valuable therapeutic agent in the treatment of obstructive pulmonary diseases.
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Most relevant research papers on this topic
Bronchodilator action of the anticholinergic drug, ipratropium bromide (Sch 1000), as an aerosol in chronic bronchitis and asthma.
Ipratropium bromide is an effective bronchodilator for both asthma and chronic bronchitis, with optimal doses of 40 to 80 mcg, and shows prolonged efficacy compared to isoproterenol.
RCT
Highly CitedIpratropium bromide-mediated myocardial injury in in vitro models of myocardial ischaemia/reperfusion.
Ipratropium bromide exacerbates myocardial ischaemia/reperfusion injury in nonclinical models, with acetylcholine acting as a protective agent.
Non-RCT
Animal Study
Rigorous JournalThe Use of Ipratropium Bromide for the Management of Acute Asthma Exacerbation in Adults and Children: A Systematic Review
Ipratropium bromide combined with beta2-agonists improves airflow obstruction and reduces hospitalization rates in acute asthma exacerbations in both adults and children without severe adverse effects.
Systematic Review[Effects of ipratropium bromide as a nebulized solution on respiratory function in mechanically ventilated patients].
Nebulized ipratropium can improve inspiratory resistance and respiratory symptom relief in ventilated patients with bronchospasms, potentially due to bronchodilatation and better airflow.
RCTTransport of ipratropium, an anti-chronic obstructive pulmonary disease drug, is mediated by organic cation/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption.
Ipratropium and tiotropium are primarily taken up by OCTN2, with a lesser extent by OCTN1, in human bronchial epithelial cells, resulting in carrier-mediated pulmonary absorption.
In Vitro StudyHighly CitedClinical pharmacology and toxicology of ipratropium bromide.
Ipratropium bromide is a promising anticholinergic drug for treating airflow obstruction, with promising effects on large- and intermediate-size airways without toxic effects.
Ipratropium bromide in asthma. A review of the literature.
Ipratropium bromide has a slower onset of bronchodilator action but longer duration than beta agonists, with potential benefits in psychogenic asthma and exercise-induced asthma.
Literature ReviewEffect of ipratropium bromide on the action of bronchoactive agents.
Ipratropium bromide has an anticholinergic effect, attenuates contractile responses to various bronchoactive agents, and may be useful for treating chronic obstructive lung diseases.
In Vitro StudySodium cromoglycate and ipratropium bromide in exercise-induced asthma.
Sodium cromoglycate and ipratropium bromide effectively inhibit exercise-induced asthma in extrinsic asthmatics, with mediator release being a key factor in asthma development.
RCTHighly CitedIpratropium bromide: bronchodilator action and effect on methacholine-induced bronchoconstriction.
Higher doses of ipratropium bromide may provide better bronchodilator effect and tolerance to methacholine in asthmatic patients, while still providing good protection against methacholine-induced bronchoconstriction.
RCT