Nebulized glyceryl trinitrate exerts acute bronchodilator effects in patients with acute bronchial asthma.

Glyceryl trinitrate (GTN) is a potent smooth muscle relaxant and vasodilator. There are conflicting reports regarding its efficacy as a bronchodilator. The aim of this study was to examine whether nebulized GTN has bronchodilating effects in patients with acute bronchial asthma. We studied 18 patients (five female, 13 male) who were admitted to the hospital with acute severe asthma on two occasions, administering either 6 mg nebulized GTN or placebo (saline) in a double-blind, randomized, crossover fashion. Bronchial response was assessed by measurement of peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). A systematic effect of this dose of GTN was demonstrated by a mean increase in heart rate of 38.1% (SEM=7.6%) after GTN administration from supine to erect posture, compared with 10.2% (SEM=1.8%) after placebo (P<0.005). Systolic blood pressure decreased by 8.7% (SEM=1.1%) after GTN, compared with 4.0% (SEM=2.1%) after placebo (P<0.05). Diastolic blood pressure did not change significantly. Baseline PEF, FEV1 and FVC did not differ on the two experimental days; however, acute bronchodilating effects were seen: PEF (l/min); 368 (21) pre-GTN, 411 (22) post-GTN and 384 (23) post-placebo (P<0.001). FEV1 (l); 2.12 (0.13) pre-GTN, 2.46 (0.15) post-GTN and 2.25 (0.16) post-placebo (P<0.001). FVC (l); 3.31 (0.17) pre-GTN, 3.75 (0.2) post-GTN and 3.54 (0.2) post-placebo (P<0.001). In conclusions, nebulized GTN has bronchodilating effects in patients with acute bronchial asthma. The exact mechanism of bronchodilation is not known, but it may be due to local effect on bronchial smooth muscles through nitric oxide or by systemic vasodilatation which leads to a decrease in pulmonary artery pressure and pulmonary vascular resistance, or an increase in systemic catecholamine release.

Dose equivalence and bronchoprotective effects of salmeterol and salbutamol in asthma.

BACKGROUND: Salbutamol is the most widely prescribed short acting beta 2 agonist and salmeterol is the first long acting inhaled beta 2 agonist. The dose equivalence of salmeterol and salbutamol is disputed. Estimates of weight-for-weight dose ratio have ranged from 1:2 to 1:16. A study was undertaken to clarify the true dose ratio. METHODS: The bronchoprotection afforded against repeated methacholine challenge by inhaled salmeterol 25 micrograms and 100 micrograms and salbutamol 100 micrograms and 400 micrograms was compared in a randomised, double blind, placebo controlled, crossover trial. Subjects were 16 stable asthmatics with a baseline forced expiratory volume in one second (FEV1) of > or = 65% predicted, screening concentration provoking a fall in FEV1 of 20% (PC20FEV1) of < or = 8mg/ml, and a shift in PC20FEV1 of more than two doubling concentration steps following inhalation of salbutamol 400 micrograms. On five separate occasions subjects underwent methacholine challenge before and 30 and 120 minutes after drug administration. PD20FEV1 was calculated for each challenge. FEV1 at 90 minutes after drug administration was also recorded. RESULTS: Bronchoprotection afforded by salmeterol was increased at 120 minutes compared with 30 minutes and protection by salbutamol was decreased. Protection by both doses of salmeterol was similar to salbutamol 100 micrograms at 30 minutes but significantly greater at 120 minutes. FEV1 at 90 minutes was significantly greater after salmeterol 100 micrograms than after placebo, but there were no other significant differences between treatments. Maximal observed protection was equivalent for salmeterol 100 micrograms and salbutamol 400 micrograms. CONCLUSIONS: The data are compatible with a weight-for-weight dose ratio for salmeterol:salbutamol of < or = 1:4.

Determination of the minimum dose of lactose drug carrier that can be sensed during inhalation.

Lactose is commonly used as a carrier for inhaled drugs. Twenty healthy volunteers without respiratory symptoms inhaled seven different doses of lactose and a placebo (empty) dose through the four place Diskhaler device, in order to determine the lowest dose that could be reliably sensed. The minimum dose for which all subjects reported taste or feel sensations was 10 mg. This has implications regarding the amount of carrier used in future drug delivery systems.

Effects of intradermal injection of atrial natriuretic peptide.

Atrial natriuretic peptide (ANP) causes mast cell degranulation in rats in vivo and in vitro but is bronchodilator in humans. The aim of this study was to investigate the wheal and flare dose-response to intradermal injection of alpha-human ANP in normal humans. Eight normal subjects received five 30 microliters injections containing 1, 10, 39, 78, 117 pmol ANP and one each of normal saline, histamine 675 pmol and substance P 30 pmol. Maximum ANP flare response was greater but not significantly than that to saline at 1.55 +/- 0.6 (mean +/- s.e. mean) compared with 0.42 +/- 0.17 cm2, but much less than to histamine 9.86 +/- 0.97 or to substance P 12.5 +/- 1.2. Maximum ANP wheal response was significantly greater than that to saline at 0.38 +/- 0.08 compared with 0.18 +/- 0.05 cm2 (difference between means 0.20, 95% CI 0.05, 0.35), but much less than to histamine 0.75 +/- 0.06 or to substance P 1.05 +/- 0.08 cm2. No dose-response to ANP was demonstrated, though responses to the highest dose differed significantly from those to the lowest dose studied. We conclude that human cutaneous responses to ANP differ from those of animals and that the skin is less responsive than other tissues in humans.

Intradermal actions of hypertonic saline involve neural and vascular mechanisms.

The aim of this study was to investigate whether the wheal and flare responses to intradermal injection of hypertonic (4.5%) saline (HTS) were inhibited by local injection of 1% lignocaine. Eight normal subjects were studied on one occasion. Lignocaine (0.125 ml) was infiltrated at four sites on one forearm and normal saline on the other. Five minutes later, duplicate intradermal injections of 30 microliters of histamine (22.5 nmol ml-1), substance P (1 nmol ml-1), HTS and normal saline were given coded and in random order, one of each pair to each forearm. Lignocaine inhibited flare responses to histamine, substance P and HTS by 56% (P < 0.01), 78% (P < 0.01) and 77% (P < 0.05) respectively suggesting similar involvement of an axon reflex. Wheal to histamine was inhibited by 31% (P < 0.02) and to substance P by 33% (P < 0.05) but not to HTS. This suggests that the mechanism of wheal response to HTS differs from that of histamine and substance P.