Ipratropium Bromide Aerosol Research Articles

Evaluation on therapeutic effects of tiotropium combined with salmeterol and fluticasone in treatment of stable COPD patients of group C

Objective To investigate the therapeutic effects of combination treatment of tiotropium plus salmeterol and fluticasone in the treatment of stable chronic obstructive pulmonary disease (COPD) patients of group C.Methods 60 subjects with stable COPD in group C classified by combined COPD assessment,were randomly divided into a treatment group (n=30) and a control group (n=30).The treatment group was treated with tiotropium(1 8 μ g,inhalation,once daily) plus salmeterol and fluticasone (50,500 μ g,inhalation,twice a day) and the control group was treated only with ipratropium bromide and albuterol aerosol according to the needs.The exercise tolerance and lung function were measured before and 8 weeks after the treatment respectively.Results 8 weeks after the treatment,there were improvements of 6 minute walk test compared with baseline and the control group,significantly greater improvements in the FVC,FEV1 and FEV1％ pred were seen in the treatment group at all time points(P＜O.05).FVC,FEV1 and FEV1％ pred 8 weeks after treatment were higher than those before treatment in both two groups(P＜O.05),but there was a significant difference between the treatment group and the control group (P＜O.05).Conclusion Combination treatment with tiotropium,salmeterol and fluticasone inhalation has greater therapeutic benefits than ipratropium bromide or albuterol aerosol inhalation alone in stable COPD patients of group C. Key words: Chronic obstructive pulmonary disease (COPD); Tiotropium; Salmeterol/Fluticasone

The effect of indacaterol during an acute exacerbation of COPD

Some clinical trials have suggested that the inhaled long-acting β2-agonists (LABAs) may be effective in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Since indacaterol, the first once-daily LABA to be developed for the regular treatment of COPD, exhibits fast onset of action and 24-h duration of bronchodilation, we have investigated its effects in patients with AECOPD managed in the emergency department.In a randomised controlled pilot trial, we have enrolled 29 consecutive patients with a recent (i.e., within ≤4 d) history of AECOPD and requiring hospitalization. All patients received a standard protocol consisting of ipratropium bromide aerosol 500 μg three times a day, intravenous methylprednisolone 20 mg twice-daily and, if indicated, oral levofloxacin 500 mg once-daily. Moreover, they were randomly allocated to one of the two 5-day treatment groups (indacaterol maleate 300 μg once-daily or salbutamol nebulizer 1250 μg three times a day).The administration of indacaterol 300 μg to patients admitted to emergency department for an AECOPD resulted in a greater improvement of pulmonary function compared with traditional therapy, without cardiovascular side effects.Our results suggest that indacaterol could be a useful option in the treatment of AECOPD. However, further larger double-blinded randomized clinical trials are needed to validate the intriguing results obtained in this setting.

Simultaneous determination of ipratropium and salbutamol in rat plasma by LC–MS/MS and its application to a pharmacokinetic study

A novel, sensitive and specific LC–MS/MS method with silica-based solid-phase extraction was developed for simultaneous determination of ipratropium (IPR) and salbutamol (SAL) in rat plasma. Chromatographic separation was achieved on a Shiseido Capcell Pak CR column (SCX:C 18 = 1:4, 150 mm × 2.0 mm, 5 μm) with a mobile phase consisting of methanol/water (85:15, v/v) containing 20 mmol/L ammonium formate and 0.1% formic acid at a flow rate of 0.3 mL/min. A tandem mass spectrometric detection with an electrospray ionization (ESI) interface was conducted via multiple reaction monitoring (MRM) under positive ionization mode. This method was validated in terms of specificity, linearity, accuracy (within ±115.4%), intra- and inter-day precision (<11.4%) over the concentration range of 8–1612 pg/mL for IPR and 50–10,000 pg/mL for SAL. In addition, stability and matrix effects of IPR and SAL in plasma were evaluated. This method has been successfully applied to the pharmacokinetic study of compound ipratropium bromide aerosol mainly containing ipratropium bromide (IB) and salbutamol sulphate (SS) after inhalation in rats.

A Patient with a Leg Rash, Pedal Edema, Renal Failure, and Thrombocytopenia

A 57-year-old man was referred for assessment and management of malaise and leg edema, which had increased 2 weeks after the onset of a productive cough, for which clarithromycin had been prescribed. His course was complicated by the development of a pruritic skin eruption. The patient’s medical history included type II diabetes mellitus of 5 years’ duration and stage III chronic kidney disease. He also had a chronic infection with hepatitis C virus (HCV)1 (genotype 1A) and had been lost to follow-up for the previous 19 years. Medications included antihypertensive drugs (calcium channel blocker, β-blocker, angiotensin-converting enzyme inhibitor, and furosemide), a lipid-lowering drug (ezetimibe), analgesics (hydromorphone HCl and acetaminophen), and ipratropium bromide aerosol. A physical examination revealed the following: blood pressure, 140/65 mmHg; pulse, 55 beats/min; temperature, 36.9 °C; oxygen saturation, 94% on room air; body mass index, 46 kg/m2. Abdominal distention was noted and felt to be compatible with the presence of ascites. The spleen was palpable. There was bilateral lower-extremity pitting edema and a hyperpigmented pretibial rash that was not palpable. Initial laboratory investigations included typical findings for electrolytes, aspartate aminotransferase, alanine aminotransferase, total bilirubin, and the international normalized ratio. The patient’s laboratory test results are summarized in Table 1⇓ . His fasting plasma glucose concentration was impaired, and his alkaline phosphatase was slightly raised. The patient was anemic and thrombocytopenic with hypoalbuminemia and an increased serum creatinine concentration. A urinalysis dipstick screen and a microscopy evaluation revealed hematuria, proteinuria, and the presence of red blood cell casts in the urine. A 24-h evaluation of urine protein excretion confirmed an abundance of protein in the urine. The glomerular filtration rate, as estimated with the Cockcroft–Gault equation, was very low. An ultrasound analysis revealed bilateral echogenic kidneys of typical size. In the setting of a …

Clarithromycin-Oral Anticoagulants Interaction

The patient was a 67-year-old man weighing 109kg with a past history of severe chronic obstructive lung disease. He was treated long term with theophylline and ipratropium bromide and salbutamol (albuterol) aerosols, experiencing exertional dyspnoea in relation to moderate effort. In March 1996, he was hospitalised with an abrupt respiratory decompensation, and a pulmonary embolism was diagnosed. Anticoagulation, initially with low molecular weight heparin and followed by oral acenocoumarol, was initiated, reaching a stable level of anticoagulation with international normalised ratios (INR) between 1.5 and 2.2 (fig. 1). In May 1996, the patient was admitted to our hospital with another respiratory decompensation. At admission the INR was 1.95 (table I, case 3). A respiratory infection was diagnosed and treatment with c1arithromycin 500mg twice daily, corticosteroids (methylprednisolone 20mg 3 times daily), and oxygen was added to his therapy. After 3 days of c1arithromycin treatment the INR had increased to 7.01, necessitating the transient suspension of acenocoumarol. No signs of bleeding were detected, and 2 days later the INR reverted spontaneously to safe therapeutic values. Clarithromycin treatment was administered for 5 more days, and during this time the INR was around 3, with a calculated dosage of acenocoumarol of7mg per week. Clarithromycin administration was finally discontinued after the completion of 10 days of therapy, and the INR returned to safe therapeutic values with acenocoumarol 11mg per week. During 12 weeks of follow-up, INR values from 1.41 to 2.05 were maintained with acenocoumarolll to 16mg per week.

Optimal particle size for beta 2 agonist and anticholinergic aerosols in patients with severe airflow obstruction.

The optimal particle size of a beta 2 agonist or anticholinergic aerosol in patients with severe airflow obstruction is unknown. Seven stable patients with a mean forced expiratory volume in one second (FEV1) of 37.9% of the predicted value inhaled three types of monodisperse salbutamol and ipratropium bromide aerosols with particle sizes of 1.5 microns, 2.8 microns, and 5 microns, respectively, and a placebo aerosol. The volunteers inhaled 20 micrograms salbutamol and 8 micrograms ipratropium bromide, after which lung function changes were determined and analysed with repeated measurements analysis of variance (ANOVA). Greater improvements in FEV1, specific airway conductance (sGaw) and maximum expiratory flow at 75%/50% of the forced vital capacity (MEF75/50) were induced by the 2.8 microns aerosol than by the other particle sizes. In patients with severe airflow obstruction the particle size of choice for a beta 2 agonist or anticholinergic aerosol should be approximately 3 microns.

Dose response study of ipratropium bromide aerosol on maximum exercise performance in stable patients with chronic obstructive pulmonary disease.

Although the bronchodilating effect of inhaled anticholinergics has been established in patients with chronic obstructive pulmonary disease (COPD), their effects on exercise capacity are still controversial. Previous studies have suggested that the standard dosage hardly affects exercise tolerance, whereas higher doses might elicit an improvement. The aim of the present study was to determine the dose of ipratropium bromide aerosol that improves exercise performance using progressive cycle ergometry in patients with stable COPD. Twenty men with stable COPD of mean (SD) age 69.2 (4.6) years and forced expiratory volume in one second (FEV1) 1.00 (0.37) 1 were studied in a randomised double blind manner. Each patient received ipratropium bromide in doses of 240 micrograms, 160 micrograms, 80 micrograms, 40 micrograms, and placebo from a metered dose inhaler (MDI) with an InspirEase spacer on five separate days. Spirometric parameters were assessed before and at 30, 60, 90, and 120 minutes after each inhalation, and pulse rate and blood pressure were also measured immediately before each spirometric measurement. Symptom limited progressive (20 watts/min) cycle ergometer exercise tests were performed 90 minutes after each inhalation. Ipratropium bromide in doses of 160 micrograms and 240 micrograms produced a greater increase in FEV1 than 40 micrograms or 80 micrograms ipratropium bromide at all time points. Doses of 160 micrograms and 240 micrograms ipratropium bromide also produced greater increases in maximal work load and maximal oxygen consumption than placebo, whereas 40 micrograms and 80 micrograms ipratropium bromide did not. There was a weak correlation between the change in FEV1 and the change in maximal work load (r = 0.45). No differences were found in pulse rate or blood pressure between the treatment and placebo groups, and no side effects were noted throughout the study. A dose of at least four times the standard dose of ipratropium bromide from an MDI with a spacer device was necessary to improve maximal cycle exercise capacity in patients with stable COPD. Although the data from cycle ergometry cannot be directly applied to exercise performed during day to day activities, it is conceivable that the recommended doses of ipratropium bromide do not elicit the optimal clinical benefits.

A comparison of the bronchodilating effects of salmeterol, salbutamol and Ipratropium bromide in patients with chronic obstructive pulmonary disease

Bronchodilator efficacy of salbutamol (200 micrograms), salmeterol (50 micrograms) and ipratropium bromide (40 micrograms) aerosols has been compared in 16 patients with stable chronic obstructive pulmonary disease (COPD) using a double-blind placebo controlled cross-over design. When absolute changes in FEV1 were used as the response criterion, efficacy of the three drugs was significantly better than placebo (P < 0.05). The onset of bronchodilatation after ipratropium bromide was slower than after salbutamol, but ipratropium induced more and longer-lasting bronchodilatation than the adrenergic drug. Salmeterol was slower but its duration was longer than salbutamol. The onset of the effect of salmeterol was slower than ipratropium bromide, but salmeterol showed, on average, superior bronchodilator efficacy compared with the anticholinergic agent, sustaining bronchodilation longer than ipratropium bromide (responses to salmeterol were significantly (P < 0.05) greater than those to ipratropium bromide from 4-12 h time period, but from 15 min to 1 h time periods response to ipratropium bromide exceeded salmeterol). The mean FEV1 area under the curve was significantly (P < 0.05) larger after salmeterol when compared to ipratropium bromide and salbutamol. Moreover, the mean FEV1 area under the curve after ipratropium bromide was significantly (P < 0.05) higher than that after salbutamol. In any case, our data showed individual differences in patient response. We conclude that salmeterol compares favourably with ipratropium bromide in terms of effects on lung function at clinically recommended doses because it has a longer duration of action than ipratropium bromide. The longer dosing intervals, which may enhance compliance, encourage its administration in patients with COPD.

The optimal particle size for parasympathicolytic aerosols in mild asthmatics

Background: the optimal particle size of a parasympathicolytic aerosol is unknown. Methods: eight stable asthmatics with a mean FEV 1 of 72% of the predicted value inhaled three types of monodisperse ipratropium bromide aerosols, with particle sizes of 1.5, 2.8 and 5 μm, respectively, and a placebo aerosol. The volunteers inhaled 8 μg ipratropium bromide, after which lung function improvement was determined. The changes in lung function were analysed with repeated measurements ANOVA. Results: according to the changes in FEV 1 and MEF 50/25 the 1.5/2.8 μm aerosol induced significantly better bronchodilatation than the 5 μm aerosol. No particle size effect was noticeable with regard to changes in R cot, VC, FVC and PEF. Conclusions: in mild asthmatics the particle size of choice for a parasympathicolytic aerosol should be ≤ 2.8 μm.

Appropriate Use of Antitussives and Protussives

As a symptom of an underlying condition, cough is one of the most common reasons patients see physicians. To the majority, a cough means that 'something is wrong' and it causes exhaustion and/or self-consciousness. Patients find these reasons as well as effects on lifestyle, fear of cancer and/or AIDS or tuberculosis to be the most troublesome concerns for which they seek medical attention. The treatment of cough can be divided into two main categories: (a) therapy that controls, prevents or eliminates cough (i.e. antitussive); and (b) therapy that makes cough more effective (i.e. protussive). Antitussive therapy can be either specific or nonspecific. Definitive or specific antitussive therapy depends on determining the aetiology or operant pathophysiological mechanism, and then initiating specific treatment. Since the cause of chronic cough can almost always be determined, it is possible to prescribe specific therapy that can be almost uniformly successful. Non-specific antitussive therapy is directed at the symptom; it is indicated when definitive therapy cannot be given. Practically speaking, the efficacy of nonspecific therapy must be evaluated in double-blind, placebo-controlled, randomised studies of pathological cough in humans. Such studies have demonstrated the efficacy of dextromethorphan, codeine and ipratropium bromide aerosol in patients with chronic bronchitis. While the preferred treatment for patients with cough due to angiotensin converting enzyme (ACE) inhibitor therapy is withdrawal of the offending drugs, it may be possible to ameliorate the cough by adding nifedipine, sulindac or indomethacin to the treatment regimen. The efficacy of protussive therapy has not been well documented. Although hypertonic saline aerosol and erdosteine in patients with bronchitis, and amiloride aerosol in patients with cystic fibrosis have been shown to improve mucus clearance, their clinical utility has not been adequately studied.

Acute bronchodilating effects of ipratropium bromide and theophylline in chronic obstructive pulmonary disease

The bronchodilator effects of a single dose of ipratropium bromide aerosol (36 μg) and short-acting theophylline tablets (dose titrated to produce serum levels of 10–20 μg/mL) were compared in a double-blind, placebo-controlled crossover study in 21 patients with stable, chronic obstructive pulmonary disease. Mean peak forced expiratory volume in 1 second (FEV 1) increases over baseline and the proportion of patients attaining at least a 15% increase in the FEV 1 (responders) were 31% and 90%, respectively, for ipratropium and 17% and 50%, respectively, for theophylline. The average FEV 1 increases during the 6-hour observation period were 18% for ipratropium and 8% for theophylline. The mean duration of action was 3.8 hours with ipratropium and 2.4 hours with theophylline. While side effects were rare, those experienced after theophylline use did involve the cardiovascular and gastrointestinal systems. These results show that ipratropium is a more potent bronchodilator than oral theophylline in patients with chronic airflow obstruction.

THE EFFECT OF INHALED FENOTEROL AND IPRATROPIUM BROMIDE ON PROPRANOLOL INDUCED BRONCHOCONSTRICTION IN THE ASTHMATIC AIRWAYS

1. The provocative dose of inhaled propranolol, (PC20P, mg/mL) needed to induce a 20% reduction in the forced expired volume in 1 s (FEV1, L) was determined for 15 adult asthmatics following randomized pre-treatment with placebo, ipratropium bromide (40, 160 micrograms) and fenoterol (200, 800 micrograms) aerosols using a double-blind protocol. 2. Fenoterol 200 micrograms, 800 micrograms increased the baseline FEV1 0.28 +/- 0.16, 0.32 +/- 0.16 L (P = 0.04, P = 0.008 respectively). Fenoterol 800 micrograms moved the PC20 P rightwards from placebo geometric mean 10.95, 95% Confidence Intervals (95% CI) 4.43-27.22 mg/mL to mean 20.41, 95% CI 10.13 to 40.64 mg/mL (P = 0.01). Fenoterol 200 micrograms was not protective; mean PC20 16.22, 95% CI 7.83-34.35 mg/mL (P = 0.08). Neither 40 or 160 micrograms ipratropium changed the FEV1 or PC20P values compared with placebo; increase in FEV1 0.15 +/- 0.27 L (P = 0.22), 0.24 +/- 0.12 L (P = 0.14) and geometric mean PC20P 16.59 +/- 0.57 mg/mL, 95% CI 8.01-34.51 mg/mL (P = 0.90), 15.58 +/- 0.66 mg/mL, 95% CI 6.72-36.05 mg/mL (P = 0.34) respectively after ipratropium treatments. 3. Bronchoconstriction induced by inhaled propranolol (P) appears to be only weakly antagonized by inhaled beta-agonist and not reduced by antimuscarinic anticholinergic aerosol. This finding argues against the activation of a cholinergic reflex to explain propranolol induced bronchoconstriction (PIB).

Reversible fraction of airway resistance in healthy children of areas with different levels of atmospheric pollutants

Reversible fraction of airway resistance (delta Raw) has been defined as the difference between airway resistances (Raw) before and after inhalative treatment with ipratropium-bromide (Atrovent) aerosols in healthy subjects. We examined delta Raw in children between 6-8 years of age living in areas with different air qualities. We found small but statistically significant (p less than 0.1) greater delta Raw for children of higher polluted areas. This could indicate that children of polluted areas possessed higher bronchial smooth muscle tone.

Direct labelling of ipratropium bromide aerosol and its deposition pattern in normal subjects and patients with chronic bronchitis.

A technique for the direct labelling of ipratropium bromide with bromine-77, with reconstitution of the drug in a metered dose inhaler so as to be identical to the commercial product, was used to study drug deposition patterns in seven normal subjects and seven patients with chronic bronchitis (mean FEV1 32% (SD 12.2%) predicted normal). The gamma camera image of the thorax was divided into a middle zone--the mediastinal zone--and the lung itself into a central zone comprising its medial third and a peripheal zone, the lateral two thirds. Measurements after 10 inhalations of labelled ipratropium bromide showed similar results for the two groups of subjects. The total lung dose inhaled was 11.2% of 203 micrograms and 11.7% of 186 micrograms in the normal subjects and the patients respectively. In contrast to the deposition patterns seen in aerosol studies using steady state inhalation methods, there was no difference in deposition pattern--that is, the distribution between the central and the peripheral lung zones--between the normal subjects and the patients with airways obstruction.

Effect of oral prednisolone on response to salbutamol and ipratropium bromide aerosols in patients with chronic airflow obstruction.

We examined the bronchodilator responses to inhalation of salbutamol (200 micrograms) and of ipratropium bromide (40 micrograms) in the morning and in the afternoon before and during a course of oral prednisolone (40 mg daily) in 15 patients with chronic, partly reversible airflow obstruction. Bronchodilatation was assessed by measuring serial peak expiratory flow rates (PEFR) for six hours after aerosol drug administration and calculating the area under the time-response curves. Eleven patients were found to be corticosteroid resistant in not attaining a baseline bronchodilatation of at least 25% during corticosteroid treatment. These patients also failed to show any enhancement of their bronchodilator responses to either salbutamol or ipratropium bromide during prednisolone administration. We therefore conclude that there is no rationale for giving or continuing corticosteroid treatment in known steroid-resistant patients in the hope of nevertheless potentiating their bronchodilator responses to salbutamol or ipratropium bromide.

Changes in tidal volume, frequency, and ventilation induced by their measurement.

Changes in tidal volume, frequency, and ventilation induced by their measurement.