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At least 163 records · Page 9Linked to original sources
PubMed1995

Reduced dose salbutamol in comparison with standard dosage for symptom relief in asthma.

Regular treatment with beta 2-agonists has been reported to be associated with an increase in risk of asthma death or near death, and with a deterioration in asthma symptom control. Low-dose beta 2-agonists provide effective bronchodilatation and bronchoprotection, even though maximal bronchodilatation is not achieved, and they may offer a better safety profile. In a double-blind, randomized,, cross-over study, we evaluated the efficacy of low-dose salbutamol metered-dose inhaler (50 micrograms.puff-1), used over a period of 2 weeks, compared with a standard dose (100 micrograms.puff-1) in control of asthma symptoms in 20 moderately severe asthmatic subjects using inhaled glucocorticosteroid therapy. Asthma control was assessed by symptom scores, peak flow rates, spirometry, inhaler usage and, where possible, by bronchial responsiveness to methacholine. Despite a 46% reduction in mean weekly salbutamol dosage, mean forced expiratory volume in one second (FEV1), morning and evening peak expiratory flow (PEF), PEF variability, dose of methacholine provoking a 20% decrease in FEV1 (PC20) (n=9), and symptom scores showed no difference between low-dose and standard inhaler treatment periods. Low-dose inhaler administration resulted in a small but significant increase in number of inhaler actuations. Low-dose salbutamol metered-dose inhaler may, thus, be useful for control of symptoms in moderately severe asthma. This strategy could be used to achieve a reduction in total beta 2-agonist usage, which may minimize any potential for adverse effects.

Administration, Inhalation↗
PubMed1997

Development and validation of an ion-pair liquid chromatographic method for the quantitation of sodium cromoglycate in urine following inhalation.

An ion-pair liquid high-performance chromatography method with solid-phase extraction for measuring urinary concentrations of sodium cromoglycate following inhalation has been developed and validated. Sodium cromoglycate was extracted from urine on a 100-mg phenyl cartridge (Isolute, Jones Chromatography) and then quantified on a 25-cm C8 Spherisorb 5 microns stationary phase with a mobile phase of methanol-0.045 M phosphate buffer-0.05 M dodecyl triethyl ammonium phosphate (550:447.6:2.4, v/v) pH 2.3, at 0.85 ml min-1 using nedocromil sodium as an internal standard and UV detection at 238 nm. The inter- and intra-day reproducibilities were 8.33 and 13.63%, respectively, at 0.25 mg l-1. The limit of determination for sodium cromoglycate was 0.25 mg l-1 (with a signal-to-noise ratio of greater than 10:1). Following oral and inhaled administration of 20 mg of sodium cromoglycate to eight healthy volunteers, the mean and S.D. of sodium cromoglycate excreted in the urine at 0.5, 1 and 24 h post-dose were 0.02, 0.05 and 0.33%, and 0.16, 0.30 and 1.55% of the dose, respectively. The urinary recovery of sodium cromoglycate at 0.5 and 1 h following inhalation can therefore be used to compare the amount of drug reaching the respiratory tract using different sodium cromoglycate inhaled products or inhalation methods.

Administration, Inhalation↗
PubMed1994

Dose-effect relationship of the beta-agonists fenoterol and salbutamol in patients with asthma.

QUESTION: What is the relative per microgram potency and side effect profile of the beta-agonists salbutamol and fenoterol? METHOD: The relative bronchodilator (delta FEV1, V25, V50) potency and side effect profile (delta tremor, heart rate, breathlessness, BP) of nebulized salbutamol and fenoterol were evaluated by means of a randomized, double-blind, crossover, cumulative (50 to 2,500 micrograms) dose-response study. Both beta-agonists were administered to 12 patients with stable asthma over age 18 years with baseline FEV1 between 35 to 70 percent predicted. RESULTS: (1) Salbutamol and fenoterol both provided significant bronchodilatation compared with baseline. (2) There was no dose-effect difference between the two beta-agonists with respect to bronchodilator response. (3) Overall there was no significant difference between the side effect profiles of the two beta-agonists, although at the highest dose of fenoterol, there was marginally greater tremor when measured by accelerometry. (4) There was no difference in the vital signs or subjective patient evaluations of tremor, palpitations, or breathlessness as estimated by a visual analogue scale. (5) No significant adverse reactions occurred. SUMMARY AND CONCLUSION: Equivalent bronchodilatation and similar side effect profiles were measured in a group of patients with stable asthma after treatment with nebulized salbutamol or fenoterol in the dose range 50 to 1,250 micrograms (cumulative, 2,500 micrograms). This indicates that both beta-agonists have similar per microgram potency and side effect profiles. Observed clinical differences in response or side effects associated with fenoterol metered-dose inhaler administration may be a result of its higher dose per puff metered-dose inhaler formulation.

Administration, Inhalation↗
PubMed1992

[Experience in the combined treatment of different clinical forms of chronic bronchitis with new phytotherapeutic mixtures].

As many as 68 patients suffering from chronic bronchitis (CB) were subjected to combined treatment by new mixtures of medicinal herbs given per os and by inhalation. Administration of the first (antiseptic) or the second (broncholytic) mixture was determined by the clinical variant of CB. In 81% of cases, the method produced a beneficial effect, contributing to the shortening of the times of the patients' treatment in the hospital. The long-term results were also positive, allowing the simultaneous use of the phytotherapeutic mixtures per os and by inhalation in the treatment of CB patients.

Administration, Inhalation↗
PubMed1996

The effect of inhaled K+ channel openers on bronchoconstriction and airway microvascular leakage in anaesthetised guinea pigs.

Since orally administered K+ channel openers may have cardiovascular side effects, it is possible that inhaled administration would be preferred for the treatment of asthma. We have investigated whether inhaled levcromakalim and HOE 234 inhibit histamine-induced bronchoconstriction and airway plasma exudation in anaesthetised guinea pigs. We have also investigated whether inhaled HOE 234 inhibits the bronchoconstriction and plasma exudation induced by vagus nerve stimulation, which is due to the release of tachykinins from sensory nerves. Lung resistance was measured by airway resistance (RL) computed from airway and transpulmonary pressures and plasma exudation by measurement of Evans blue dye extravasation. Inhaled levcromakalim (25 mu g/ml) had a short duration of action, being effective against histamine-induced bronchoconstriction 2 min after pretreatment, but not at 10 min. Inhaled HOE 234 (25 mu g/ml) was similarly effective against histamine-induced bronchoconstriction but had a longer duration of action. Inhaled levcromakalim partially attenuated histamine-induced plasma extravasation in small airways, but not in the trachea or main bronchi, whereas inhaled HOE 234 had no effect. HOE 234 protected against non-adrenergic non-cholinergic nerve-induced bronchoconstriction, but had no effect on neurogenic- or substance P-induced plasma extravasation in the airway. Inhaled K+ channel openers protect against induced bronchoconstriction, but provide little or no protection against plasma exudation, possibly because of an increase in airway blood flow. In addition, inhaled HOE 234 had no effect on neurogenic leakage, suggesting that its vagal inhibitory effect on bronchoconstriction was on airway smooth muscle, rather than on release of neuropeptides from sensory nerves.

Administration, Inhalation↗
PubMed1995

The effect of inhaled and oral dextromethorphan on citric acid induced cough in man.

1. Dextromethorphan is a widely used antitussive agent which is a non-narcotic codeine analogue. We have investigated whether inhaled administration of dextromethorphan provides antitussive activity in a citric acid induced cough model. 2. Twenty normal subjects underwent repeated cough challenge with 5% citric acid. Subjects were studied on six occasions. Study medication consisted of oral dextromethorphan 30 mg or oral matched placebo or 1, 3 and 30 mg inhaled dextromethorphan or matched inhaled placebo. Cough challenge was administered 10 min after study medication and hourly thereafter up to 250 min. 3. No significant differences were seen between baseline cough responses. Oral dextromethorphan (30 mg) produced a mean percentage reduction in cough of 38% (P < 0.002), which remained significant at 250 min. Inhaled dextromethorphan had no clinically significant effect although activity at later time points was not excluded. The antitussive effect of oral dextromethorphan is confirmed with prolonged inhibition of induced cough. It is possible that dextromethorphan or its active metabolites act centrally to inhibit the cough reflex.

Administration, Inhalation↗
PubMed2005

Potent effects of aerosol compared with intravenous treprostinil on the pulmonary circulation.

Inhaled vasodilator therapy for pulmonary hypertension may decrease the systemic side effects commonly observed with systemic administration. Inhaled medications only reach ventilated areas of the lung, so local vasodilation may improve ventilation-perfusion matching and oxygenation. We compared the effects of intravenous vs. aerosolized treprostinil on pulmonary and systemic hemodynamics in an unanesthetized sheep model of sustained acute pulmonary hypertension. Acute, stable pulmonary hypertension was induced in instrumented unanesthetized sheep by infusing a PGH(2) analog, U-44069. The sheep were then administered identical doses of treprostinil either intravenously or by aerosol. Systemic and pulmonary hemodynamics were recorded during each administration. Both intravenous and aerosol delivery of treprostinil reduced pulmonary vascular resistance and pulmonary arterial pressure, but the effect was significantly greater with aerosol delivery (P < 0.05). Aerosol delivery of treprostinil had minimal effects on systemic hemodynamics, whereas intravenous delivery increased heart rate and cardiac output and decreased left atrial pressure and systemic blood pressure. Aerosol delivery of the prostacyclin analog treprostinil has a greater vasodilatory effect in the lung with minimal alterations in systemic hemodynamics compared with intravenous delivery of the drug. We speculate that this may result from treprostinil stimulated production of vasodilatory mediators from pulmonary epithelium.

Acute Disease↗
PubMed2001

Inhalation of [123I]alpha1-protease inhibitor: toward a new therapeutic concept of alpha1-protease inhibitor deficiency?

UNLABELLED: The alpha1-protease inhibitor (alpha1-Pi) is separated from human serum and is therefore extremely expensive. Because only 2%-3% concentrates in the lung after intravenous administration, inhalational therapy for alpha1-Pi deficiency would seem likely to be better. The aims of this study were therefore to determine the pattern of deposition of inhaled alpha1-Pi labeled with 123I and measure the amount deposited in the lungs. METHODS: Eighteen patients with congenital severe alpha1-Pi deficiency were enrolled in the study. The low-specific-activity 123I-labeled alpha1-Pi aerosol (median particle size +/- SD, 3.9 +/- 2.5 microm) was generated by an air pressure-driven nebulizer. The patients inhaled for an average of 23.6 +/- 8.9 min. Static scintigrams in two projections were acquired immediately after (T1) and 1 (T2), 4 (T3), and 24 h (T4) after inhalation. The patients were divided into the following three groups according to their forced expiratory volume in 1 s (FEV1): group I, < or =40% of predicted normal (n = 8); group II, 40% < FEV1 < or = 60% of predicted normal (n = 4); group III, >60% of predicted normal (n = 6). RESULTS: The absolute percentage uptake values of alpha1-Pi in group I were 12.4 for T1, 7.3 for T2, 4.6 for T3, and 1.2 for T4; in group II the values were 13.0, 9.6, 6.2, and 2.0, respectively; and in group III, 14.6, 11.4, 6.5, and 3.6, respectively. Differences between the groups were generally statistically significant. Between T1 and T2, the probability value was <0.05 for group I versus group II, <0.006 for group I versus group III, and <0.39 for group II versus group III. Between T1 and T3, the probability value was <0.29 for group I versus group II, <0.22 for group I versus group III, and <0.94 for group II versus group III. Retention (between T1 and T4) was also dependent on the grade of the disease: P < 0.2 for group I versus group II, P < 0.001 for group I versus group III, and P < 0.02 for group II versus group III. Grading of the uptake pattern by three independent experienced investigators (87% agreement) revealed a peripheral deposition that was group dependent. We found that greater peripheral deposition corresponded with lower lung functional impairment: P < 0.5 for group I versus group II, P < 0.01 for group I versus group III, and P < 0.08 for group II versus group III. Degradation also corresponded with functional impairment: P < 0.05 for group I versus group II, P < 0.006 for group I versus group III, and P < 0.3 for group II versus group III. CONCLUSION: The results of this study show that sufficient amounts of alpha1-Pi can be deposited in the periphery of the lung by inhalation at least in patients with low-grade disease. Inhalation of alpha1-Pi may thus represent a new and more convenient route of drug administration.

Administration, Inhalation↗