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Biomedical subjects

N Svedmyr

Publications and source records attributed to N Svedmyr.

At least 19 recordsLinked to original sources
PubMed1997

The lack of respiratory effects of the ocular hypotensive drug latanoprost in patients with moderate-steroid treated asthma.

The use of beta blockers for glaucoma treatment may cause serious bronchoconstriction in patients with chronic obstructive pulmonary disease. The synthetic prostaglandin (PG) F2 alpha-analogue latanoprost (13,14,dihydro-17-phenyl-18,19,20-trinor-PGF-2-alpha-iso propylester) represents a new class of drugs for glaucoma treatment. In this study the pulmonary tolerability to latanoprost in 12 healthy volunteers and 11 (one withdrawal due to a sty before latanoprost treatment) subjects with moderate but stable steroid-treated intrinsic asthma was examined. Asthmatic subjects received 30 microliters of vehicle (placebo) at the scheduled administration times on baseline day. On a second day, a minimum of one week later, increasing concentrations (0.35, 115 and 350 micrograms/ml) of latanoprost were added to the vehicle and given topically to both eyes. Healthy volunteers were given latanoprost only. ECG, blood pressure, heart rate, forced expiratory volume (FEV1), peak expiratory outflow (PEF) and forced vital capacity (FVC) were recorded immediately prior to and 15, 30, 45 and 60 minutes after latanoprost. Asthmatic patients inhaled salbutamol (0.2 mg) at 60 minutes after the highest latanoprost dose. There were no significant differences in pulmonary function, blood pressure or heart rate after latanoprost in the healthy volunteers. Moreover, all parameters were unaffected in asthmatic patients on the day latanoprost was given compared to the baseline day. Latanoprost did not dampen the bronchodilator response to beta-2-adrenergic stimulation. It is concluded that latanoprost did not affect lung function in healthy subjects or in asthmatics after a total accumulated dose 10 times that clinically recommended for glaucoma treatment. Therefore, latanoprost appears to be safe for glaucoma treatment in patients with steroid-treated stable moderate intrinsic asthma.

Administration, Inhalation↗
PubMed1997

Differences in bronchodilating potency of salbutamol in Turbuhaler as compared with a pressurized metered-dose inhaler formulation in patients with reversible airway obstruction.

Two studies are presented, with the aim of establishing the dose potency ratio for salbutamol given via Turbuhaler and via a pressurized metered-dose inhaler (pMDI). Both studies were of a double-blind, randomized design. Outpatients with mild-to-moderate chronic reversible airway obstruction were given single doses of salbutamol administered via Turbuhaler and via pMDI. Efficacy and safety variables were measured before and during 6 h after each dose. The first study was a four-way crossover study including 12 patients. The salbutamol doses given were: 50, 100 and 2x100 microg via Turbuhaler and 2x100 microg via pMDI (Ventolin). The study showed that 2x100 microg of salbutamol inhaled via Turbuhaler is more potent than 2x100 microg salbutamol inhaled via a pMDI, and that 100 microg salbutamol via Turbuhaler is at least as potent as 2x100 microg salbutamol inhaled via a pMDI. The second study including 50 patients was a placebo-controlled five-way crossover, study. Two doses of salbutamol via Turbuhaler, 50 and 2x100 microg, and via pMDI, 100 and 2x200 microg, were given. There was a dose-dependent response in forced expiratory volume in one second (FEV1) for both inhalers. Adjusted for differences in baseline FEV1 values, the estimated relative dose potency for Turbuhaler versus pMDI was 1.98:1 (95% confidence interval 12-3.2). These studies showed that the same bronchodilating effect can be achieved when half the dose of salbutamol given via a conventional pressurized metered-dose inhaler is given via Turbuhaler.

Administration, Inhalation↗
PubMed1996

Formoterol inhaled as dry powder or via pressurized metered-dose inhaler in a cumulative dose-response study.

Formoterol administered by a dry-powder (DP) capsule inhaler was compared with a pressurized metered-dose inhaler (pMDI) with regard to bronchodilating and systemic effects. The study used a double-blind, crossover, double-dummy technique. Twelve patients with moderate reversible asthma in a stable phase were examined on two separate study days, and the inhalers were given in randomized order. After baseline measurements, increasing doses of formoterol were given at intervals of 75 min. FEV1 and heart rate and tremor measurements were repeated after each dose, and the doses were 12 + 12 + 24 + 48 micrograms, giving a total dose of 96 micrograms. The peak expiratory flow rate (PEFR) was recorded in the morning before the first dose, after the last dose, and then repeatedly at home until 19 h after the last dose. There was an equal increase in ventilatory capacity at each dose level, independent of inhaler device. Repeated PEFR measurements after the last dose did not reveal any differences in duration of effect. There was a slight but statistically significant increase in heart rate and tremor after the highest doses of the DP formulation compared to the pMDI. These systemic effects can probably be explained by the reduced oral deposition of the aerosol caused by using a spacer. This study indicates that the DP and pMDI formulations of formoterol are equipotent in bronchodilation.

Administration, Inhalation↗
PubMed1996

The use of beta 2-adrenoceptor agonists in the treatment of bronchial asthma.

All guidelines recommend short-acting inhaled beta 2-adrenoceptor agonists as the first-line drugs in acute asthma attacks and inhaled corticosteroids as the drugs of choice when regular daily treatment is needed. Short-acting inhaled beta 2-adrenoceptor agonists are not effective in reducing nocturnal awakenings because of their short duration of action. In addition there has been an intense debate about the regular use of these drugs. This debate is reviewed. They should only be used on "as needed basis". The Swedish guidelines for the treatment of asthma were the first to recommend the new long-acting inhaled beta 2-adrenoceptor agonists at relatively early stage of the illness (800 micrograms daily of inhaled corticosteroids). Two recently completed large multicentre studies with salmeterol in asthmatics support this opinion. Both studies showed a better asthma control with a combination of a low inhaled steroid dose and salmeterol compared to a doubling of the steroid dose. In most asthmatic patients, still symptomatic on inhaled steroids doses 400 to 800 micrograms daily, a test of the addition of inhaled salmeterol is recommended. The steroid dose can be kept low and safe. However, asthmatic patients with either frequent or severe exacerbations should primarily have their steroid dose increased.

Adrenergic beta-2 Receptor Agonists↗
PubMed1994

Airway effects of direct left-sided cervical vagal stimulation in patients with complex partial seizures.

Airway nerves have been implied in obstructive lung diseases for many years. In experimental animals, vagal stimulation produces several features of asthma, including airflow obstruction and airway plasma exudation. Vagal stimulation is a novel and effective therapy in patients with refractory epilepsy. We evaluated the airway response to left-sided cervical electrical stimulation using 1 Hz (low stimulation: 30 s, once every 90 min) and 30 Hz (high stimulation: 30 s, every 5 min) in a randomized double-blinded fashion for 3 months in epileptic patients participating in a phase two efficacy study. In eight patients with high stimulation and six with low stimulation, no effect on FEV1 (forced expiratory volume in 1 s) was seen over 3 months chronic stimulation. In a follow-up, up to 9 months, no further deterioration of lung function was observed. Of five patients without concomitant lung disease who consented to more extended experiments, one patient produced a reduction of FEV1 with variable frequency and current stimulation (10-87 Hz and 0.5-2.5 mA respectively). In one patient with obstructive lung disease, however, increased frequency and current stimulation led to a stimulation-dependent decrease in FEV1. After the addition of inhaled ipratropium bromide (160 micrograms, dry powder) to this patient, there was a clear improvement of baseline FEV1, but only a slight improvement of the stimulation-induced deterioration of FEV1. We conclude that long-term vagal stimulation in patients without concomitant lung disease does not induce any significant changes in FEV1. However, in patients with obstructive lung disease, intense vagal stimulation can cause a deterioration of lung function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Salmeterol: an inhaled beta 2-agonist with prolonged duration of action.

Salmeterol (Serevent) is an inhaled beta 2-receptor agonist with more than twelve hours' effect duration compared with 4-6 hours for the more short-acting substances bitolterol, fenoterol, salbutamol, and terbutaline. Salmeterol has been studied in several large-scale double-blind multicenter studies with up to one year's duration. More than 6,000 asthmatics have been treated with salmeterol during these controlled studies. All studies show salmeterol to have a significantly better and well-maintained bronchodilating effect with better asthma control, fewer asthma exacerbations, and a decreased need for rescue albuterol inhalations used on demand compared to the treatments in the control groups (200-400 micrograms albuterol q.i.d., inhaled albuterol given only p.r.n., terbutaline given regularly, or individually titrated slow-release theophylline). Salmeterol should be given b.i.d. and in combination with inhaled corticosteroids. Salmeterol seems especially effective in patients with nocturnal symptoms, exercise induced asthma, and in patients sensitive to inhaled irritants such as cold air. The patients should always have short-acting inhaled beta 2-agonists available for break-through attacks. Inhaled salmeterol in combination with inhaled steroids seems to give the best maintenance asthma control available by inhalation today.

Administration, Inhalation↗
PubMed1992

Late asthmatic reaction decreased after pretreatment with salbutamol and formoterol, a new long-acting beta 2-agonist.

The inhibitory effect of salbutamol and formoterol, a new long-acting beta 2-agonist for inhalation, on the late asthmatic reaction (LAR), was studied in 12 patients with allergic asthma. After a single-blind, placebo-treatment control, equipotent bronchodilating doses of inhaled salbutamol (500 micrograms) and formoterol (30 micrograms) were administered 30 minutes before bronchial allergen challenge in a double-blind randomized design. The early asthmatic reaction was completely inhibited by both drugs (p less than 0.01) but not by placebo. The LAR was also significantly inhibited by both drugs (p less than 0.01); formoterol was only slightly, but significantly, more effective than salbutamol (p = 0.04). In contrast to some earlier studies, the present study indicates an inhibitory effect of beta 2-agonists on the LAR.

Adrenergic beta-Agonists↗
PubMed1992

Twelve months, treatment with inhaled salmeterol in asthmatic patients. Effects on beta 2-receptor function and inflammatory cells.

Salmeterol is a new beta 2-receptor agonist with a prolonged duration of action after inhalation, exceeding 12 h in most patients. We have performed a 12-month open follow-up study on 11 patients with reversible asthma. All patients were given salmeterol inhalations (50 micrograms twice daily). Additional asthma treatment included inhaled corticosteroids in all patients, and oral slow-release theophylline or beta 2-receptor agonists in a minority of patients (3 and 1, respectively). Before salmeterol treatment was initiated and after 3, 6, 9 and 12 months of salmeterol treatment, a cumulative dose-response curve to inhaled salbutamol (100, 300 and 900 micrograms) was performed, and FEV1 measured. We also evaluated the effect of each salbutamol dose on finger tremor, systemic blood pressure and heart rate. Blood tests, including white blood count and electrolytes, were taken at each visit. After salmeterol treatment was initiated, morning FEV1, measured before the morning asthma medication, was significantly improved (p < 0.05). The responsiveness to inhaled salbutamol was not decreased during salmeterol treatment, except in one patient with asthma worsening over the study year. Baseline finger tremor measured before salbutamol dose-response curves, was significantly lower at the 12-month visit than before treatment was initiated (p < 0.05). Effects of salbutamol on systemic blood pressure, heart rate or finger tremor was not significantly changed during salmeterol treatment. We found a successive and significant decrease in blood eosinophils (p < 0.05) during the 12 months of salmeterol treatment, when the patient with asthma worsening was excluded in the analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

Bronchodilator intake and plasma levels on admission for severe acute asthma.

We have measured the plasma levels of salbutamol, terbutaline and theophylline in 140 patients (70 men, mean age 57 yrs) arriving for emergency treatment with severe acute asthma. The aim of the study was to investigate how the measured plasma levels correlated with the reported bronchodilator intake and whether the pretreatment beta 2-agonist levels influenced the effect of emergency salbutamol treatment. We found a highly significant correlation between the reported 24 h dose and the measured plasma concentrations for all three drugs. A plasma concentration less than 40 mumol.l-1 was found in 63 of the 107 patients who had taken theophylline, while no patient had a plasma concentration greater than 110 mumol.l-1. A plasma concentration above the suggested therapeutic range was found in 23 of the 95 patients who had taken terbutaline (greater than 30 nmol.l-1) and in 12 of the 98 patients who had taken salbutamol (greater than 60 nmol.l-1). A significant negative correlation was found between the initial plasma beta 2-agonist levels and the bronchodilation after i.v. salbutamol treatment (5 micrograms.kg-1), while there was no clear indication that high plasma beta 2-agonist levels reduced the bronchodilator effect of a high dose of inhaled salbutamol (0.15 mg.kg-1 x 2). We conclude that some patients arriving with acute asthma have high blood concentrations of beta 2-agonists, which possibly limit the response to i.v. beta 2-agonist treatment, while the effect of high-dose inhaled beta 2-agonists appears to be related to a lesser degree to the drug concentration on arrival. In this study overtreatment with theophylline appears to be uncommon.

Acute Disease↗
PubMed1991

Tetrodotoxin does not block the epithelium-dependent release of prostaglandin E2 induced by electrical field stimulation in isolated ferret trachea.

Electrical field stimulation (EFS) has previously been shown to induce the release of prostaglandin (PG) E2 from ferret tracheal epithelium. We have now conducted a study to see whether this effect of EFS is due to the activation of nerves or whether it is a non-neural effect. The release of PGE2 and 6-keto-PGF1 alpha into the bath fluid was assayed in isolated ferret tracheas with (E+) or without (E-) epithelium, stimulated by either EFS or direct vagal nerve stimulation (DNS) repeatedly for 120 min. EFS-stimulated E+ preparations showed a gradual decline in the contractile responses (30 +/- 1% of baseline) and an increase in PGE2 to 296 +/- 38 pg/ml. In EFS-stimulated, epithelium-denuded (E-) preparations, the decline was significantly lower (11 +/- 5%), as well as the final concentration of PGE2 (107 +/- 21 pg/ml). In DNS-stimulated E+ preparations, the contraction decline was 8 +/- 1% and the final concentration of PGE2 was less than 6 pg/ml. Although tetrodotoxin (TTX) abolished the contractile response in EFS-stimulated E+ preparations, it did not significantly reduce the release of PGE2 (260 +/- 6 pg/ml), whereas atropine partly counteracted the release. The bath concentration of 6-keto-PGF1 alpha increased, independently of the electrical stimulation, contractile response, or presence of the epithelium. We conclude that EFS activates the epithelium-dependent release of PGE2 by a TTX-resistant mechanism. This may be due to an activation of TTX-resistant nerves, or possibly to a non-neural effect, such as a direct effect on the epithelial cells. The results indicate that the airway epithelium has the ability to respond to certain stimuli with a pronounced release of PGE2, thereby counteracting bronchoconstriction.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Inhaled formoterol during one year in asthma: a comparison with salbutamol.

Eighteen patients, who had previously taken part in a 2 wk cross-over comparison between formoterol and salbutamol, now took part in a one year double-blind study comparing salbutamol 200 micrograms b.i.d. with formoterol 12 micrograms b.i.d. Additional doses were taken when needed and were recorded. Ten patients were started on formoterol and eight on salbutamol. After one month, the patients were allowed to shift to the alternative drug. Two patients withdrew from the study. At the end of the study, 13 of 16 patients were on formoterol, thus showing a long-lasting preference for this drug. Forced expiratory volume in one second (FEV1) dose-response curves for inhaled salbutamol were repeatedly recorded during the study, and no tachyphylaxis was found. One patient stopped taking inhaled steroids but continued taking formoterol and theophylline. He deteriorated with a decreased response to salbutamol. After re-introduction of inhaled steroids his condition improved. This case indicates that effective bronchodilator therapy may mask the deterioration of asthma.

Administration, Inhalation↗
PubMed1990

The current place of beta 2-agonists in the management of asthma.

Inhaled beta 2-stimulants are the most effective drugs for acute asthma attacks. This is probably due to the functional antagonism against a large variety of possible asthma mediators. A slight rebound increase of bronchial hyperreactivity 12 to 23 h after stopping regular treatment has been proposed. This finding is not well documented and must be further studied. There is no convincing evidence that tachyphylaxis of clinical importance to the bronchodilating effect occurs in asthmatics receiving normal doses of beta 2-receptor stimulants but cannot be totally excluded. Candidates for regular inhaled beta 2-agonist treatment always have inflammation in their airways and should be given inhaled steroids. Steroids not only seem to reduce airway inflammation and hyperreactivity but they also reverse beta 2-receptor subsensitivity in experimental studies. Patients on purely prophylactic antiasthmatic drugs should be instructed always to carry their beta 2-stimulants inhalers.

Administration, Inhalation↗
PubMed1990

Epithelium-derived PGE2 inhibits the contractile response to cholinergic stimulation in isolated ferret trachea.

We have previously reported that epithelium-dependent inhibitory factors, both prostanoids and non-prostanoids, can be activated by electrical field stimulation (EFS) and direct nerve stimulation (DNS) in an in vitro nerve-muscle preparation of ferret trachea. In this study we set out to compare the release of the inhibitory prostanoids, PGE2 and PGI2, in preparations with intact and with removed epithelium. Ferret tracheae were mounted in organ baths and phasic contractions were induced by EFS and DNS. The bath concentrations of PGE2 and the PGI2-metabolite 6-keto-PGF1 alpha were measured using radioimmuno assays. The gradual decrease in contractile response to DNS, 2 Hz for 120 min, was 95 +/- 2% of baseline (mean +/- SEM) in preparations with intact epithelium compared with 29 +/- 8% in epithelium-denuded preparations (p less than 0.001). The bath-levels of PGE2 showed a slight but significant (p less than 0.01) increase in denuded preparations with a final bath-concentration at 120 min of 13 +/- 3 pg/ml. The release of PGE2 was more pronounced in preparations with intact epithelium which resulted in a final bath-concentrations of PGE2 of 84 +/- 38 pg/ml which was significantly higher compared with epithelium-denuded preparations and also compared with time-matched controls with the same pattern of contraction induced by DNS alone. The concentrations of 6-keto-PGF1 alpha showed a slight increase which was of comparable magnitude (ns) in intact and denuded preparations. In conclusion this study demonstrates that the cyclooxygenase-dependent component of the epithelium-dependent inhibition of the contractile response to cholinergic nerve stimulation in ferret trachea is mediated by PGE2 but not by PGI2.

6-Ketoprostaglandin F1 alpha↗