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Seven asthmatic patients were studied in a single-blind randomized, crossover study after oral administration of 20 mg nifedipine or placebo. Four increasing doses of i.v. terbutaline were then given with 30 min interval. The study was concluded with inhalation of five terbutaline puffs. FEV1 measurements 30 min after intake of nifedipine did not show any difference compared to placebo. During the terbutaline treatment, however, there was a more pronounced bronchodilation after nifedipine than after placebo (P less than 0.05). Terbutaline-induced skeletal muscle tremor was similar after nifedipine and placebo pretreatments. After nifedipine intake there was a decrease of diastolic blood pressure and a reflexogenic tachycardia. Thus, this study showed a small potentiation of the beta 2-adrenoceptor mediated bronchodilation, which is of importance when treating patients with simultaneous asthma and hypertension or angina pectoris.

The influence of pretreatment with equipment bronchodilating doses of intravenous theophyllamine and inhaled terbutaline on the effect of five terbutaline inhalations was investigated in a cross-over study in six adult asthmatics with stable and reproducible bronchoconstriction. Theophylline in a dose giving a maximal mean plasma concentration of 16.7 +/- 1.21 micrograms/ml (92 mumol/l) gave far from maximal acute bronchodilation as the following five terbutaline inhalations gave the same further bronchodilation. Pretreatment with five terbutaline inhalations induced almost equal bronchodilation compared with theophyllamine but the following five inhalations now gave only about one-fourth of the effects recorded after theophyllamine pretreatment. This potentiation could, however, be due to the different routes of administration of the pretreatments. In a randomized, double-blind, cross-over study in eight asthmatic, pretreatment with equipotent oral bronchodilating doses of theophylline and terbutaline was shown to give the same potentiation of the following five terbutaline inhalations. Theoyphylline orally as such thus did not potentiate the effect of inhaled beta 2-stimulants. It had only the same effect as oral terbutaline, but induced less tremor. This means that the potentiation after intravenous and oral pretreatment was not due to theophylline but to the different routes of administrations. Systemic administration probably gave a better distribution and thus better effect of the inhaled terbutaline.

The acute ventilatory, cardiovascular and tremorogenic effect of a high oral dose of terbutaline (5 mg) was compared with that of half the dose (2.5 mg) combined with 280 mg anhydrous theophylline orally in the randomized, double-blind, cross-over study in eight asthmatics. After 120 min, when steady-state bronchodilation was achieved, five terbutaline inhalations (1.25 mg terbutaline sulphate) were added to both treatment regimens. The mean maximum plasma concentration of theophylline was then 7 micrograms/ml (39 mumol/l). Inhalation of a beta 2-adrenostimulant had a very good additional effect without increasing side effects in these patients with good inhalation technique. The oral low-dose combination gave significantly better bronchodilation than the high dose of terbutaline alone and caused significantly less tremor. Although the combination only had an additive bronchodilating effect, it may offer important clinical advantages. If the patient cannot use the metered dose aerosol, an oral low dose combination should be preferred to a single high dose of either theophylline or beta 2-adrenostimulants. In patients with good inhalation technique but not controlled by inhalation from a metered dose aerosol alone, a combination of oral theophylline and terbutaline in "sub-optimal" dose and an inhaled beta 2-agonist in individually titrated optimal dose gave a maximal bronchodilating effect with minimum side effects.

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