Bronchodilatory therapy with nebuhaler: how important is the delay between firing the dose and inhaling?

Metered dose inhalers are sometimes used in conjunction with NebuhalerR, a 750 ml holding chamber, but the permissible delay time between actuating the aerosol into Nebuhaler and commencing inhalation is unknown. We have compared in 10 asthmatic patients the bronchodilator responses following inhalations of terbutaline sulphate from Nebuhaler after delays of 1, 5 and 30 seconds and following placebo inhalation. Terbutaline sulphate was administered as 2 puffs, each of 250 micrograms, separated by approximately 15 minutes. After each delay time, terbutaline produced increases in forced expiratory volume in one second (FEV1), peak expiratory flow rate (PEFR) and maximum expiratory flow following exhalation of 75% of the forced vital capacity (V max25) significantly greater than those after placebo (P less than 0.01). Changes in PEFR did not vary significantly among the three delay times, but the increases in FEV1 and in V max25 were significantly reduced with 30 seconds' delay. It is concluded that the delay between actuation into Nebuhaler and commencing inhalation can be extended from 1 second to 5 seconds without significant loss of drug efficacy, and that further extension to 30 seconds causes only a small loss of bronchodilatation: hence the delay time is unlikely to be of major importance in clinical practice.     

Sex differences in the production of methaemoglobinaemia by 4-aminopropiophenone

A methaemoglobin former, 4-aminopropiophenone (p-aminopropiophenone, PAPP), which is active only after metabolic activation in vivo, exhibits a sex difference in male Beagle dogs and bitches. Bitches produced more methaemoglobin for a given dose of PAPP than male dogs. The probable reason for this difference was a lower rate of N-hydroxylation in male dogs.