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  • Plasma exudation  (1)
  • antagonism  (1)
  • bronchodilatation  (1)
  • 1
    ISSN: 1432-1041
    Keywords: Nasal airways ; Plasma exudation ; Xanthine derivatives ; fibrinogen ; bradykinins ; terbutaline ; theophylline ; nasal mucosa ; nasal lavage ; histamine provocation test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Experimental data suggest the possibility that common bronchodilators, such as the xanthines and β2-adrenoceptor agonists, may produce microvascular anti-permeability effects in the subepithelial microcirculation of the airways. In this study, we have examined the effect of bronchodilators given intravenously on exudation of differentsized plasma proteins (albumin and fibrinogen) and the generation of plasma-derived peptides (bradykinins) in human nasal airways challenged with histamine. In a double-blind, crossover, placebo-controlled and randomised trial, 12 normal volunteers were given IV infusions of terbutaline sulphate, theophylline and enprofylline to produce therapeutic drug levels. The effect of topical nasal provocation with histamine was closely followed by frequently nasal lavage with saline. The lavage fluid levels of albumin, fibrinogen and bradykinins increased significantly after each histamine provocation. The ratio of albumin-to-fibrinogen in plasma and the lavage fluid was 24 and 56, respectively, indicating that topical histamine provocation induced a largely non-sieved flux of macromolecules across the endothelial-epithelial barriers. The systemically administered drugs did not affect the nasal symptoms (sneezing, secretion and blockage), nor did they significantly reduce the levels of plasma proteins and plasma-derived mediators in the nasal lavage fluids. The present data suggest that systemic xanthines and β2-adrenoceptor agonists, at clinically employed plasma levels, may not affect the microvascular (and epithelial) exudative permeability and the bradykinin forming capacity of human airways.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: enprofylline ; theophylline ; obstructive lung disease ; adenosine ; antagonism ; bronchodilatation ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Enprofylline, a xanthine-derivative shown experimentally to lack universal adenosine receptor antagonism, has been examined in patients with partly reversible, chronic, obstructive lung disease. Significant bronchodilation was produced by enprofylline 2 mg/kg, giving a peak plasma concentration of 3.0±0.6 µg/ml (mean ± SD). A dose of 2+4 mg/kg dilated the bronchi at least to the same extent as theophylline 9.2±0.9 mg/kg (plasma level 18.5±4.7 µg/ml). Neither at the low nor at the high dosage (2+4 mg/kg), giving plasma concentrations of 8.5±1.4 µg/ml, did enprofylline produce theophylline-like CNS effects, such as restlessness and tremor, but it did exhibit some of the innocuous side effects expected with xanthine derivatives, such as epigastric discomfort and headache. The comparison with theophylline was limited because different dosage forms had to be used (solution and tablets), which for example, resulted in different absorption rates. Nevertheless, the present findings indicate enprofylline to be a potent bronchodilator in patients with obstructive lung disease, suggesting that adenosine-receptor antagonism is not involved in the bronchodilator effects of xanthines.
    Type of Medium: Electronic Resource
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