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Evaluation of airway pharmacodynamic and pharmacokinetic properties of bronchoconstrictor and bronchodilator drugs in normal human subjects
Başlık:
Evaluation of airway pharmacodynamic and pharmacokinetic properties of bronchoconstrictor and bronchodilator drugs in normal human subjects
Yazar:
Hassan, Nageeb A.G.M, author.
ISBN:
9780355977776
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (308 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Özet:
In 26 normal volunteers, their individual responsiveness to inhaled, nebulized methacholine (MeCh) was studied, using a standardized bronchial challenge test and measuring specific airway conductance (sGaw) using whole body plethysmography. This study suggested that their airway responsiveness (AR) to inhaled MeCh is composed of independent sensitivity (ED 50, PD 35) and reactivity (E., the slope of the log dose-response curve (LDRC)) components. In 11 of the volunteers their individual AR to inhaled, nebulized histamine was measured. The reactivity component is larger than that to MeCh. The relative potency between them varies with the effect amplitude at which it is assessed. In an individual subject, the PD 35 of either one bronchoconstrictor agent can not be adequately predicted by just knowing that of the other. An approximately steady state reduction from baseline sGaaw was induced in 20 of the subjects by an individualized MeCh loading dose and maintenance dose regime and cumulative doses of salbutamol were inhaled. This study suggested that 1) the AR to salbutamol is composed of independent sensitivity and reactivity components; 2) there is a general relationship between the sensitivities to salbutamol and MeCh, and between the reactivities to salbutamol and MeCh; there is little relationship across these parameters; 3) it is less the amount of constriction produced but more the amount of MeCh producing it that determines the AR to salbutamol; 4) the more MeCh that is used the more salbutamol is needed for the same degree of antagonism i.e. the lower is the responsiveness to it and this arises more from a reduction of sensitivity than reactivity. 12 of the subjeCts sustaining a background bronchoconstfiction to MeCh inhaled 2 different formulations of the xanthine analogue SDZ MKS 492. This produced dose-dependent broncho-dilatation that was small and transient, unaccompanied by any effect on blood pressure or pulse rate. It had a bitter taste that was not masked by inclusion of menthol and aspartame in the formulation. 8 of the subjects sustaining a background bronchoconstriction to MeCh or histamine inhaled cumulative doses of ipratropium or salbutamol. Salbutamol was equally effective and potent in antagonizing MeCh and histamine. Ipratropium and salbutamol were equally effective in antagonizing MeCh. The slope of the LDRC is a not valid index of reactivity between bronchodilator agents with different mechanisms of action. The bronchomotor tone in normal subjects is entirely cholinergic in origin. Histamine, at the doses employed, reduces sGaw chiefly by a direct action on H1 receptors on airways effectors and not by a vagally mediated mechanism. 6 of the subjects sustaining a background bronchoconstriction to MeCh inhaled 3 different formulations of salbutamol; Aerolin Autohaler, Rotacaps and Respirator solution (Nebulized). This study suggested that 1) all formulations achieved a peak bronchodilator effect within 9 min that remained for 10 min; 2) Rotacaps was more potent than Aerolin Autohaler but equipotent with Nebulized. Aerolin Autohaler was equipotent with Nebulized; 3) the effect of Rotacaps (200 ?g) wore off more rapidly than Nebulized (140 jig) but not than Aerolin Autohaler (100 ?g). Aerolin Autohaler and Nebulized showed similar rates of offset. Most of the subjects during MeCh individualization showed a shallow offset time effect curve. About 30% showed the initial rapid offset time effect curve. Four MeCh inhalation experiments, devised to explore the causation, suggested that 1) it is not the amount of bronchoconstriction induced or the dose of MeCh inhaled that induces an initial rapid rate of offset but the cumulative method of administration; 2) the difference is due to the release of inhibitory PGs. (PGs).
Notlar:
School code: 1543
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(683813.1) | 683813-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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