ENHANCED HISTAMINE H I RECEPTOR BLOCKADE WITH CHLORPHENIRAMINE IN THE ASTHMATIC TRACHEO-BRONCHIAL TREE: FURTHER EVIDENCE FOR INCREASED DRUG DELIVERY IN ASTHMA
نویسندگان
چکیده مقاله:
We have measured the competitive antagonistic effect of chlorpheniramine in bronchi of 8 normal and 12 asthmatic subjects. Classical pharmacological theory states that the degree of competitive antagonism depends only upon 1) antagonist concentration at the receptor, and 2) receptor affinity. Delivery and affinity also influence agonist responsiveness, but measurement of bronchial antagonism allows study of these factors in isolation. Bronchial responsiveness to histamine was measured as the dose required to produce a 35% fall in specific conductance (sGaw), called PD35• On different days, 2 measurements of control PD35 were made on each subject. Measurements of PD35 were also repeated after inhalation of 1.45 mg chlorpheniramine and intravenous injection of 0.17 mg/kg chlorpheniramine. Antagonist effect of chlorpheniramine was measured as Dose Ratio-l (DR-I), where DR= PD35 after chlorpheniramine/control PD35• Geometric mean of DR -1 with inhaled chlorpheniramine in asthmatic subjects (5.8) was 6.8 times that of normal subjects (0.86) (p= 0.002), and DR-l with intravenous chlorpheniramine in asthmatic subjects (4.4) was 2.75 times that of normal subjects (1.6) (p=0.005). There were significant negative correlations between PD35 and DR-I, whether chlorpheniramine was administered by inhalation (r= -0.87, p<O.OO 1) or intravenously (r= -0.62, p<0.005). There was also a significant correlation between DR-1 obtained by two routes of administration (r= 0.77, p<0.001). Taken with our previous study showing enhanced antagonism with atropine at bronchial muscarinic receptors in asthma, I these results suggest that drug delivery by inhaled and parenteral routes may be increased in asthmatic bronchi.
منابع مشابه
enhanced histamine h i receptor blockade with chlorpheniramine in the asthmatic tracheo-bronchial tree: further evidence for increased drug delivery in asthma
we have measured the competitive antagonistic effect of chlorpheniramine in bronchi of 8 normal and 12 asthmatic subjects. classical pharmacological theory states that the degree of competitive antagonism depends only upon 1) antagonist concentration at the receptor, and 2) receptor affinity. delivery and affinity also influence agonist responsiveness, but measurement of bronchial antagonism al...
متن کاملINCREASED HISTAMINE Hi RECEPTOR BLOCKADE BY CHLORPHENIRAMINE IN TRACHEAL CHAINS OF ASTHMATIC GUINEA PIGS
Receptor affinity and drug delivery to the receptor sites could be determinant factors for the increased bronchial responsiveness seen in asthma. Competitive antagonism blockade which is measured as dose ratio-l (DR-I) depends only on these two factors. Therefore, in this study we have examined histamine HI blockade by chlorpheniramine on isolated tracheal chains of asthmatic compared to co...
متن کاملH2 receptor blockade and bronchial hyperreactivity to histamine in asthma.
The role of histamine H1 and H2 receptors in the lung is not clear. H1 receptor blockade results in bronchodilatation and inhibition of histamine induced bronchoconstriction. H2 receptor blockade in vitro prevents the normal negative feedback of histamine on further mediator release in antigen challenge. Bronchospasm in guinea pigs given antigen challenge is enhanced by previous administration ...
متن کاملSHORT TERM VARIATION OF ATROPINE BLOCKADE IN THE TRACHEOBRONCHIAL TREE OF ASTHMATIC SUBJECTS
In asthmatic subjects there is a pronounced diurnal variation in bronchial responsiveness. If this phenomenon is due to variation in factors that control drug delivery, then it should be paralleled by a similar variation in competitive antagonist blockade. In order to study this possibility, we performed the methacholine challenge test and after 45 minutes, administered atropine by inhalat...
متن کاملAsthma-Like Tracheo-Bronchial Amyloidosis
Localized bronchial Amyloidosis is an uncommon disease of unknown origin. Clinical signs are not specific. Tracheobronchial symptoms are the most frequent. We report a case of a 31 year-old man complaining of asthma-like dyspnea. Bronchoscopy was performed because of ineffectiveness of antiasthmatic treatment, showed a submucosal infiltration with stenosis of both right and left upper bronchi a...
متن کاملModern imaging of the tracheo-bronchial tree.
Recent state-of-the-art computed tomography and improved three-dimensional (3-D) postprocessing techniques have revolutionized the capability of visualizing airway pathology, offering physicians an advanced view of pathology and allowing for appropriate management planning. This article is a comprehensive review of trachea and main bronchi imaging, with emphasis on the dynamic airway anatomy, a...
متن کاملمنابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ذخیره در منابع من قبلا به منابع من ذحیره شده{@ msg_add @}
عنوان ژورنال
دوره 11 شماره 2
صفحات 115- 122
تاریخ انتشار 1997-08
با دنبال کردن یک ژورنال هنگامی که شماره جدید این ژورنال منتشر می شود به شما از طریق ایمیل اطلاع داده می شود.
میزبانی شده توسط پلتفرم ابری doprax.com
copyright © 2015-2023