[On the problem of Side Effects of Anticholinergic Drugs Depending on the Route of Application/Inhalation versus intravenous injection of ipratropiumbromide].

In four different trial series the effect of (8r)-3alpha-hydroxy-8-isopropyl-1alphaH, 5alphaH-tropanium-bromide-(+/-)-tropate (ipratropiumbromide, Sch 1000, Atrovent) on the stimulated salivary secretion and pulse rate in a total of 43 healthy volunteers was investigated in a cross-over comparison using atropine sulphate and placebo administered by inhalation (metered dose inhaler) and by i.v. injection. All the trial preparations were administered in increasing doses at 30-min intervals in a double-blind procedure. The maximal dose by inhalation in this context was 2.4 mg (60 times the single therapeutic dose), and the maximal i.v. dose was 0.28 mg. The stimulated salivary secretion was not influenced by doses up to 2.4 mg of ipratropiumbromide by inhalation. Following inhalation of 1.6 mg and 2.4 mg atropine sulphate by means of metered dose inhaler of linear, statistically significant inhibition of stimulated salivary secretion was observed (p less than 0.001). Following i.v. administration of ipratropiumbromide, a statistically significant decrease in stimulated salivary secretion was observed following a total dose of 0.28 mg (p less than 0.001). Following inhalation the changes in pulse rate all occurred within the placebo or confidence limits. Following i.v. administration the pulse rate showed a statistically significant increase after a total dose of 0.28 mg. Dryness of the mouth was observed by several volunteers following the maximum dose of ipratropiumbromide, All volunteers in this trial series observed dryness of the mouth inhalation of atropine sulphate.