Salbutamol-induced airway hyperreactivity in guinea pigs is not due to a loss of its bronchodilator effect

Sympathomimetic enantiomers and asthma

“…Sustained infusion of racsalbutamol has made possible the demonstration of hyperreactivity in response to rac-salbutamol. [60][61][62] Thus, whereas an infusion of rac-salbutamol initially provided complete protection of sensitised guinea-pigs exposed to antigen, this protection waned with time; by 24 hours, all animals collapsed but none died and, after 48 hours or more of continuous subcutaneous infusion (1 mg/kg/day), animals consistently collapsed and died upon exposure to antigen. However, these compromised animals were responsive to sympathomimetics, since they survived if given supplementary doses of sympathomimetics (inhaled racisoprenaline or subcutaneous rac-salbutamol at the time of exposure to antigen).…”

“…This has been independently confirmed by the demonstration that, whereas sensitivity to the bronchodilator action of salbutamol was unimpaired 24 hours after terminating a subcutaneous infusion of salbutamol (200 µg/kg/day for 10 days), hyperreactivity to acetylcholine, histamine, and bombesin was pronounced. 61 In passively sensitised guinea-pigs, modest allergic reactions (increasing basal airway resistance by <10%) induce hyperreactivity of the airways. 63 In such animals, infusion of rac-salbutamol (1 mg/kg/day) for 6 days prior to infusion of a low dose of antigen induced an exaggerated airways reactivity to spasmogens, and hence a more pronounced allergic bronchospasm.…”

Treatment with High Doses of Terbutaline Induces β-Adrenergic Desensitization of Guinea Pig Trachea Not Prevented by the Addition of Dexamethasone

“…However, the airway smooth muscle appears to have a special resistance to β 2 -adrenergic desensitization, probably due to a rapid turnover of the β 2 -adrenergic receptors [21]. Some studies, using low or medium doses, failed to find desensitization of the guinea pig trachea, although they demonstrated an increase in the response to metacholine or acetylcholine after in vivo salbutamol [22]or in vivo and in vitro fenoterol [23]treatment of guinea pigs. Moreover, an increase in airway responsiveness to indirectly acting stimuli after regular treatment with salbutamol or terbutaline has been described in asthmatic patients [24, 25].…”

Measurement of albuterol in guinea pig serum by high performance liquid chromatography with fluorescence detection

“…The safety of these drugs has been questioned, particularly when they are used chronically (Sears et al, 1990). Clinical (Cheung et al, 1992;O'Conner et al, 1992) and experimental (WittEnderby et al, 1993;Buchheit et al, 1995;Morley, 1996;Loss and Orzechowski, 1998) evidence supports a possibility that, under some circumstances, b 2 -adrenoceptor agonists paradoxically induce airway hyperreactivity to bronchoconstrictors.…”

“…1), as an internal standard (Miller and Greenblatt, 1986). We applied our method to measure serum concentrations of albuterol from guinea pigs receiving the drug by continuous subcutaneous infusion, at a dose that induces airway hyperreactivity in vivo (Buchheit et al, 1995) and in vitro (Loss and Orzechowski, 1998 Standards. Albuterol hemisulfate salt and bamethan sulfate salt were initially weighed and the concentrations of the standard solutions were based on the weight of the salt form of both drugs.…”