Pharmacological dissection of the immediate asthmatic reaction
Pharmacological dissection of the immediate asthmatic reaction
This thesis examines the role of histamine, the prostaglandins and adenosine in the immediate asthmatic reaction by the use of specific receptor antagonists or inhibitors of mediator synthesis. Terfenadine was found to be a potent and selective histamine H1 receptor antagonist in human airways and in the skin. Pretratment with terfenadine 180mg reduced the immediate bronchoconstrictor reaction to inhaled allergen by 50% in a group of atopic asthmatics. In a double-blind, crossover study, treatment with terfenadine during the hay fever season reduced symptoms of cough and wheeze in a group of grass pollen sensitive asthmatics and increased peak expiratory flow despite a 40% reduction in bronchodilator use. In both atopic asthmatics and non-asthmatics the cyclooxygenase inhibitor flurbiprofen reduced the immediate allergen induced bronchoconstriction by 25% but when combined with terfenadine, was not more effective than the antihistamine alone implying that complex interactions occur between the cyclooxygenase products and histamine. The specific thromboxane TP receptor antagonist CR32191 produced a similar degree of inhibition to that of flurbiprofen. Adenosine is a naturally occuring purine nucleoside that is released under conditions of hypoxia or following allergen challenge. The bronchoconstrictor response to the inhalation of adenosine monophosphate, a precursor of adenosine, was inhibited by 86% after pretreatment with terfenadine or astemizole suggesting that its bronchoconstrictor effect may be mediated largely by the secondary release of histamine. Repeated inhalation of AMP rendered the airways of atopic non-asthmatics unresponsive to the constrictor effect of AMO and this effect persisted for 4 hours. The evidence presented suggests that up to half of the immediate bronchoconstrictor response to inhaled allergen is attributable to the release of histamine and one quarter due to the production of the constrictor prostanoids. The bronchoconstrictor effects of adenosine are predominantly due to the secondary release of mast cell mediators.
University of Southampton
1989
Rafferty, Paul
(1989)
Pharmacological dissection of the immediate asthmatic reaction.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
This thesis examines the role of histamine, the prostaglandins and adenosine in the immediate asthmatic reaction by the use of specific receptor antagonists or inhibitors of mediator synthesis. Terfenadine was found to be a potent and selective histamine H1 receptor antagonist in human airways and in the skin. Pretratment with terfenadine 180mg reduced the immediate bronchoconstrictor reaction to inhaled allergen by 50% in a group of atopic asthmatics. In a double-blind, crossover study, treatment with terfenadine during the hay fever season reduced symptoms of cough and wheeze in a group of grass pollen sensitive asthmatics and increased peak expiratory flow despite a 40% reduction in bronchodilator use. In both atopic asthmatics and non-asthmatics the cyclooxygenase inhibitor flurbiprofen reduced the immediate allergen induced bronchoconstriction by 25% but when combined with terfenadine, was not more effective than the antihistamine alone implying that complex interactions occur between the cyclooxygenase products and histamine. The specific thromboxane TP receptor antagonist CR32191 produced a similar degree of inhibition to that of flurbiprofen. Adenosine is a naturally occuring purine nucleoside that is released under conditions of hypoxia or following allergen challenge. The bronchoconstrictor response to the inhalation of adenosine monophosphate, a precursor of adenosine, was inhibited by 86% after pretreatment with terfenadine or astemizole suggesting that its bronchoconstrictor effect may be mediated largely by the secondary release of histamine. Repeated inhalation of AMP rendered the airways of atopic non-asthmatics unresponsive to the constrictor effect of AMO and this effect persisted for 4 hours. The evidence presented suggests that up to half of the immediate bronchoconstrictor response to inhaled allergen is attributable to the release of histamine and one quarter due to the production of the constrictor prostanoids. The bronchoconstrictor effects of adenosine are predominantly due to the secondary release of mast cell mediators.
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Published date: 1989
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Local EPrints ID: 461015
URI: http://eprints.soton.ac.uk/id/eprint/461015
PURE UUID: f006acc0-fb24-4920-868f-77f6e2b99631
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Date deposited: 04 Jul 2022 18:34
Last modified: 04 Jul 2022 18:34
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Author:
Paul Rafferty
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