Bronchodilatation after inhalation of the antihistamine clemastine.

Abstract

(1978). Thorax, 33, 479482 Bronchodilatation after inhalation of the antihistamine clemastine. H, receptor blocking antihistamines administered by mouth have not found a clear place in the management of bronchial asthma. We investigated the possibility that higher concentrations of these drugs, administered directly to the bronchial tree, might produce bronchodilatation.Twelve asthmatic patients inhaled aerosols generated from solutions of clemastine (0 05%0), salbutamol (0 5%), and placebo. Bronchodilatation was assessed by changes in the forced expiratory volume in one second (FEVY) and peak expiratory flow rate (PEFR) over four hours.Both clemastine and salbutamol caused significant bronchodilatation. The mean maximum percentage increases in FEV, for clemastine and salbutamol were 21 1 % and 29 2% respectively. The mean maximum percentage increases in PEFR were 31-2% and 35-2% respectively. There was no significant difference in the maximum bronchodilatation produced by the two drugs.Clemastine, when administered by aerosol inhalation, appears to be an effective bronchodilator.The role of histamine in the production of acute asthma is controversial. There is evidence that histamine is released in allergic reactions in the lung (Schild et al, 1951), and challenge studies have shown that the bronchi of asthmatics are more sensitive to histamine than those of nonasthmatics (Curry, 1947;Tiffenau, 1958;Townley et al, 1965). Oral antihistamine drugs have not found a place in treating asthma, however, and are widely thought to be ineffective (Lancet, 1955).Assuming that histamine plays a role in asthma, the therapeutic failure of antihistamines could be due either to the failure to block the H2 receptor sites or to incomplete H, receptor blockade caused by inadequate local concentrations of drugs. Indeed, higher doses of antihistamines, given by mouth or parenterally, have caused bronchodilatation (Popa, 1977), but central nervous system depression limits their use by this route.We have attempted to assess whether the administration of an H, receptor blocking antihistamine, clemastine, given directly to the bronchi as an aerosol, could cause therapeutically useful bronchodilatation. PatientsTwelve patients (age range 29-70, mean 46) gave informed consent. All were in hospital having recovered from a severe exacerbation of bronchial asthma and were in a relatively stable clinical state. All had previously shown reversibility of airways obstruction by a greater than 15% increase in peak expiratory flow rate (PEFR) after inhaling salbutamol aerosol 200 ,ug. Six of the twelve patients were atopic by prick skin testing. On three consecutive mornings each patient had baseline measurements of PEFR (the best of three recordings) using a Wright peak flow meter and forced expiratory volume in one second (FEV1) using a dry wedge spirometer (Vitalograph). Each subject then inhaled from a Wright's nebuliser 1 ml each of either clemastine 0-05% in saline, salbutamol 0 5%, or physiological saline as 479 on 10 May 2018 by guest....

Pulmonary aerosol actions of LY188695 (KB2413), a new potent H1-receptor antagonist

“…This explanation could account for the comparatively low effectiveness of clemastine after the 3 minute drug treatment. In human asthmatics, Nogrady et al [5] reported that the peak bronchodilating effect of clemastine aerosol did not occur until 60 minutes after treatment. If LY 188695 had no systemic effects when delivered by aerosol, then skin responses to histamine should not have been affected for any of the aerosol treatments in experiment D. If its aerosol effect was entirely due to rapid systemic absorption, then aerosol and intravenous administration results could be expected to be comparable.…”

“…In one study [5], the bronchodilating effect of clemastine aerosol was found to be similar to that of the inhaled B2-receptor agonist salbutamol. Recent reports [8][9] concerning the new potent Hi-receptor antagonist LY188695 (KB2413) indicated that it may be a good candidate for aerosol administration.…”

Inhaled antihistamines--bronchodilatation and effects on histamine- and methacholine-induced bronchoconstriction.

“…When given by inhalation they are more effective but can cause cough, throat irritation, and occasionally, bronchoconstriction (Herxheimer, 1948(Herxheimer, , 1949Hawkins, 1955). Inhalation of clemastine causes bronchodilatation comparable to that produced by salbutamol aerosol and is without observed side effects (Nogrady et al, 1978).…”

“…In an earlier study (Nogrady et al, 1978) we showed that the H1-receptor blocking antihistamine, clemastine, administered as an aerosol from a Wright nebuliser was a potent bronchodilator with a prolonged action, and without observed side effects. As most antihistamines have anticholinergic side effects the current study was undertaken to investigate the relative importance of anticholinergic and specific H1-receptor blocking functions of clemastine inhalation in producing bronchodilatation.…”

Bronchodilator effects of clemastine, ipratropium, bromide, and salbutamol in preschool children with asthma.

“…3 Anticholinergic drugs are effective in older children and adults with asthma but there is no information on their use in the preschool child. A new anticholinergic agent, ipratropium bromide, is now available and is said to be preferable to atropine, because it produces less tachycardia and a smaller reduction in sputum flow.…”