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PubMed1982

A comparison of ketotifen with clemastine, ipratropium bromide and sodium cromoglycate in exercise-induced asthma.

Exercise-induced asthma (EIA) was provoked by a standardized treadmill running for 8 min in seven atopic adult asthmatics. The tests were performed using a double-dummy technique after placebo, oral ketotifen, inhaled clemastine, ipratropium bromide and sodium cromoglycate (SCG), in a random single blind-fashion on different days. The mean post-exercise percentage fall in forced expiratory volume in 1 sec (FEV1) was 47 (s.e. 6.95), 39 (s.e. 8.35), 27 (s.e. 7.17), 23 (s.e. 7.69) and 7.0 (s.e. 4.62)% respectively. There was significantly less mean bronchoconstriction with SCG (P less than 0.01), ipratropium bromide and clemastine (P less than 0.05) but not with ketotifen. Six out of seven individual patients had significant protection of EIA with sodium cromoglycate, four with ipratropium bromide, three with clemastine but only one with ketotifen. Ipratropium bromide and clemastine were bronchodilators at rest, whereas SCG and ketotifen were not. Despite its claims to work as a mast cell stabilizing drug, ketotifen in a single dose does not have an effect similar to sodium cromoglycate in EIA, nor does it compare with inhaled clemastine or ipratropium bromide.

Adolescent↗
PubMed1981

Heat sensitization of bacterial spores after exposure to ethidium bromide, acriflavine, or daunomycin.

A 20-min exposure of 10(7) unmodified spores of either Bacillus subtilis NCTC 3610 (harvested from potato-dextrose agar plus manganese) or Bacillus megaterium ATCC 19213 (harvested from nutrient agar plus manganese) per ml to 5 microgram of ethidium bromide per ml did not kill the spores (recovered on TAM [thermoacidurans agar modified]-plus thymidine medium). However, in both cases, the ability to survive various heat treatments was reduced after exposure of the spores to ethidium bromide. With B. subtilis, a 10-min heat treatment at 85 degrees C of unexposed spores resulted in an 85% survival rate, whereas only 50% of the ethidium bromide-exposed spores survived. With B. megaterium similar results were obtained at 75 degrees C; 77% of the unexposed spores survived, whereas only 31% of the ethidium bromide-exposed spores survived. Similarly, a 10-min exposure of B. subtilis spores to 0.005 microgram of acriflavine per ml did not kill unheated spores; however, the ability of the spores to survive exposure at 85 degrees C for 10 min was reduced to 40%. After exposure to 10 microgram of daunomycin per ml, the survival rate was 35%. Binding studies with ethidium bromide showed strong binding to spores, but as yet, the site of binding is unknown.

Acridines↗
PubMed1984

Nebulised ipratropium bromide and sodium cromoglycate in the first two years of life.

In a double blind crossover trial, we compared sodium cromoglycate, ipratropium bromide, and water in 23 asthmatic children less than 2 years old (mean age 11.8 months). Each child received nebulised solutions containing 20 mg of sodium cromoglycate, 250 micrograms of ipratropium bromide, or 2 ml water three times a day for three two month periods. Daily symptom scores did not show significant differences between the treatments but parental preferences indicated that both sodium cromoglycate and ipratropium bromide were superior to placebo. Sodium cromoglycate was prophylactic and was more likely to help the older patients. Ipratropium bromide produced an immediate clinical benefit and the response was not age dependent. We were unable to pick responders from non-responders on the basis of lung function tests performed on a routine outpatient basis. Both ipratropium bromide and sodium cromoglycate help some but not all asthmatic children aged less than 2 years.

Aerosols↗
PubMed1988

Comparison of the efficacy of preservative free ipratropium bromide and Atrovent nebuliser solution.

The paradoxical bronchoconstriction observed with commercially available isotonic ipratropium bromide nebuliser solution (Atrovent) in patients with asthma results from an adverse reaction to the preservatives, benzalkonium chloride and ethylenediaminetetra-acetic acid (EDTA). The airway response to inhaled Atrovent and preservative free ipratropium bromide nebuliser solutions has been examined in a double blind study. On separate occasions 30 asthmatic subjects inhaled 2 ml of the solutions and airway calibre was measured in terms of FEV1 for 45 minutes. Atrovent nebuliser solution provoked a greater than 20% fall in FEV1 in five of the 30 subjects, whereas this did not occur after preservative free ipratropium bromide. Inhalation of the preservative free solution resulted in more rapid and greater overall bronchodilatation than Atrovent, with mean maximum increases in FEV1 of 29.2% and 18.5% respectively. It is concluded that the risk of paradoxical bronchoconstriction with ipratropium bromide is considerably reduced by removal of benzalkonium chloride and EDTA and that preservative free ipratropium bromide is a more potent bronchodilator than the currently available Atrovent solution.

Airway Resistance↗
PubMed1994

Effect of long term treatment with oxitropium bromide on airway secretion in chronic bronchitis and diffuse panbronchiolitis.

BACKGROUND: Anticholinergic bronchodilator drugs improve lung function in chronic bronchitis but less is known of their effects on the volume and physical properties of sputum in conditions associated with excessive airway secretions. This study examines the effects of the regular use of oxitropium bromide in such patients. METHODS: The study was conducted in a parallel, double blind, placebo controlled fashion. Patients were divided into two groups: the first group (n = 17) received oxitropium bromide from a metered dose inhaler (two puffs three times daily; 100 micrograms/puff) for eight weeks, and the second group (n = 16) received placebo. Lung function was measured as forced expiratory volume in one second (FEV1) and vital capacity. In evaluating airway secretion, daily amount of expectorated sputum, percentage solid composition, viscoelastic properties including elastic modulus and dynamic viscosity, and sputum microbiology were determined. RESULTS: Oxitropium bromide increased FEV1 and decreased the mean (SE) sputum production from 61(4) to 42(3) g/day after treatment, whereas placebo had no effect. Bacterial density and sputum flora were unchanged, but solid composition and elastic modulus increased from 2.52(0.43)% to 3.12(0.34)%, and 68(12) dyne/cm2, respectively, in the group taking oxitropium bromide. CONCLUSIONS: Regular treatment with oxitropium bromide not only improves airflow limitation but also reduces sputum production, probably through the inhibition of both mucus secretion and water transport, the latter component being predominant.

Adult↗
PubMed1995

Comparison of nebulised salbutamol and ipratropium bromide with salbutamol alone in the treatment of chronic obstructive pulmonary disease.

BACKGROUND: Patients admitted with acute exacerbation of chronic obstructive pulmonary disease (COPD) are often prescribed ipratropium bromide in combination with a beta 2 agonist such as salbutamol. Studies have not shown any benefit in adding ipratropium bromide to salbutamol in acute exacerbations of COPD, but these studies have only assessed patients for 60-90 minutes and short term studies may not predict long term clinical response. Combination therapy with the two drugs was compared with salbutamol alone in the treatment of acute exacerbations of COPD during a hospital admission. METHODS: Seventy patients admitted to hospital with an acute exacerbation of COPD were randomly allocated to receive either nebulised salbutamol 5 mg and ipratropium bromide 500 micrograms, or nebulised salbutamol 5 mg alone (all four times a day) on admission. All other treatment was prescribed at the discretion of the attending physician. Length of stay in hospital and spirometric values on days 1, 3, 7, 14, and discharge were assessed. Patients completed a subjective symptom score each day. RESULTS: There was no difference between the two groups in the mean (SD) length of stay (salbutamol 10.5 (4.7) days, salbutamol + ipratropium bromide 11.8 (4.4) days; 95% CI -1.02 to 3.62). There was no difference in spirometric values on days 1, 3, 7, 14, or discharge between the two groups. The subjective improvement was similar with both treatments. CONCLUSIONS: The routine addition of nebulised ipratropium bromide to salbutamol appears to be of no benefit in the treatment of acute exacerbations of COPD.

Administration, Inhalation↗
PubMed1982

Maximal expiratory flows and forced vital capacity in normal, asthmatic and bronchitic subjects after salbutamol and ipratropium bromide.

A total of 2,880 maximum expiratory flow-volume curves were performed in a controlled double-blind cross-over examination designed to evaluate the bronchodilating effects of two different nebulized doses of salbutamol (1.75 and 0.875 mg) and ipratropium bromide (0.175 and 0.0875 mg) inhaled by 8 normal, 8 asthmatic, and 8 bronchitic subjects. FEV1, FVC, and flows at 50% FVC and at three fixed volumes below TLC have been measured over a period of 6 h on the maximum expiratory flow-volume curve. In the normal subjects, salbutamol seems to have a smaller bronchodilating effect than ipratropium bromide both at high and low lung volumes. After salbutamol the average initial FEV1 increased from 4.0 to 4.3 liters, whereas after ipratropium bromide it increased to 4.4 liters. In our asthmatic patients the initial response to salbutamol was much larger than to ipratropium bromide. After salbutamol FEV1 increased from 1.8 to 2.7 liters in 60 min, whereas after ipratropium bromide it increased to 2.4 liters in 120 min. In our bronchitic patients the difference between the two drugs seems to be very small. After both drugs FEV1 increased from 1.6 to 2.1 liters. The choice of drug for treatment of the condition would then depend on how well the individual patients tolerate the two drugs.

Adult↗
PubMed1985

Influence of 0.2 mg ipratropium bromide on mucociliary clearance in patients with chronic bronchitis.

14 patients with chronic bronchitis were subdivided into 2 groups of 7 patients. They were given at random 10 puffs of placebo or ipratropium bromide (0.2 mg). The mucociliary clearance rate was measured immediately after ipratropium inhalation (group 1) or 24 h after ipratropium inhalation (group 2). In group 1, the mucociliary clearance after ipratropium bromide was significantly better than after placebo (p less than 0.01). In group 2 there was no difference in the mucociliary clearance rates measured after ipratropium bromide or placebo, but the clearance rate still tended in favour of ipratropium bromide. We conclude that ipratropium bromide should be inhaled in high doses (0.2 mg) by hypersecretory patients with chronic bronchitis to improve mucociliary transport.

Adult↗
PubMed1986

Dose-response relationship: fenoterol, ipratropium bromide and their combination.

The beta agonist fenoterol, the antimuscarinic ipratropium bromide and their combination were compared in 10 patients with stable reversible airway obstruction. A single-blind cross-over design was used in order to obtain cumulative dose-response curves. The dose inhaled by an IPPB apparatus on different days were: fenoterol, from 12.5 to 1.600 cumulate micrograms; ipratropium bromide, from 5 to 640 cumulate micrograms; combination (5:2), from 17.5 to 1.120 cumulate micrograms. The bronchodilator effect was measured as changes of FEV1 and of SGaw. Data were processed in order to identify the median effective dose (ED50) and the percentage change at ED50 (RED50). The mean ED50 in micrograms (+/- SD) resulted in: Fenoterol, ED50 (FEV1) = 132 (+/- 46); ED50 (SGaw) = 172 (+/- 62); Ipratropium bromide, ED50 (FEV1) = 14 (+/- 7); ED50 (SGaw) = 23 (+/- 11); Combination, ED50 (FEV1) = 109 (+/- 26); ED50 (SGaw) = 121 (+/- 53). The mean RED50% (+/- SD) resulted in: Fenoterol, RED50 (FEV1) = 30 (+/- 16); RED50 (SGaw) = 106 (+/- 78); Ipratropium bromide, RED50 (FEV1) = 21 (+/- 10); RED50 (SGaw) = 82 (+/- 66); Combination, RED50 (FEV1) = 35 (+/- 11) RED50 (SGaw) = 135 (+/- 81). The ED50 (FEV1) of the combination was significantly lower (p less than 0.05) than that of fenoterol. This increased potency of the combination supports evidence for an overadditive interaction between fenoterol and ipratropium bromide. Moreover, the efficacy of fenoterol (RED50) is enhanced by combining the two drugs.

Adult↗
PubMed1986

Acute controlled study of the dose-response relationship of fenoterol, ipratropium bromide and their combination.

A double-blind study was carried out in a group of 9 patients with partially reversible airway obstruction, to evaluate the bronchodilator effect of gradually increased doses of fenoterol (cumulative doses: 100, 200, 400, 800 and 1,600 micrograms), ipratropium bromide (40, 80, 160, 320 and 640 micrograms) and a combination of these (100 + 40, 200 + 80 micrograms, etc.), denominated Duovent. The three treatments were carried out at random at the same time on 3 days, usually not consecutive days, whereby 1, 1, 2, 4 and 8 puffs (altogether 1, 2, 4, 8 and 16 doses) of each product were given in identical pressurized aerosols at intervals of 60 min. Respiratory (spirometry and flow-volume curve) and cardiovascular (blood pressure, heart rate) parameters were measured under basal conditions and 60 min after each administration. On average, with all three products, the bronchodilatory effect showed a linear correlation with the logarithm of the dose given. With the same number of puffs the side-effects (tremor in particular) of the combination fenoterol and ipratropium bromide or Duovent (FIB) were markedly fewer than those of fenoterol, while ipratropium bromide was very well tolerated. The three dose-response curves (parallel) show that, in respect of an increase in FEV1, 1 puff of Duovent (100 micrograms fenoterol + 40 micrograms ipratropium bromide) is approximately equal to 2 puffs of fenoterol (200 micrograms) and 4 puffs of ipratropium bromide (160 micrograms). FIB, therefore, makes it possible to maintain the same bronchodilatory effect as the full dose (400 micrograms) of fenoterol while improving the therapeutic value.

Adult↗
PubMed1986

Studies of ipratropium bromide and fenoterol administered by metered-dose inhaler and aerosolized solution.

Two double-blind, placebo-controlled studies were performed in patients with chronic, partially reversible airflow limitation to compare ipratropium bromide and fenoterol administered singly with the combination treatment. In the first study, ipratropium bromide, 40 micrograms, or placebo was administered 2 h before fenoterol, 400 micrograms, or placebo, both by metered-dose inhaler. The combined treatment demonstrated significant additive bronchodilatation with an improved forced expiratory volume in 1 s (FEV1) response from 3 to 6 h after fenoterol administration. In the second study, ipratropium bromide, 0.5 mg, fenoterol, 2.0 mg, or placebo was administered by aerosolized solution with a nebulizer. The FEV1 response to the combined treatment, administered at the same time, was significantly greater than for fenoterol (0.5, 0.75, 4 and 6 h) and for ipratropium bromide (0.25-1.5, and 4 h) at various times. There was a disproportionate increase in forced vital capacity (FVC) compared with FEV1 for all treatments, suggesting dilatation and increased stability of small airways. In both studies, no synergistic effect is implied. In summary, additive bronchodilatation may be achieved with combined ipratropium bromide and fenoterol treatment by metered-dose inhaler or aerosolized solution.

Aerosols↗
PubMed1997

Therapeutic equivalence of a novel HFA134a-containing metered-dose inhaler and the conventional CFC inhaler (Berodual) for the delivery of a fixed combination of fenoterol/ipratropium bromide. A randomized double-blind placebo-controlled crossover study in patients with asthma.

The efficacy and safety of a novel fenoterol/ipratropium bromide metered-dose inhaler (MDI) formulated with a non-chlorinated propellant, HFA134a, has been compared with placebo and the conventional chlorofluorocarbon (CFC)-containing fenoterol/ipratropium bromide inhaler (Berodual) in asthmatic patients. Fifty-two patients were enrolled in two centres. The fenoterol/ ipratropium bromide treatment produced significantly (P < 0.0001) greater bronchodilatation than placebo. There were no significant differences between the mean peak and average forced expiratory volume in the first second (FEV1) for patients receiving 2 puffs of the fenoterol/ipratropium bromide HFA134a inhaler and the conventional CFC inhaler. In addition, time to onset and duration of efficacy were comparable for these two treatments. None of the patients showed a fall of > or = 15% in baseline FEV1 or needed rescue medication within 30 min after inhalation of the test drug. No paradoxical bronchoconstriction was observed as measured by sGaw. The two inhaler formulations were well tolerated. A taste-related complaint, lasting for a few minutes after inhalation, was reported by a higher proportion of patients who inhaled the HFA134a formulation, mainly by patients selected in one of the two centres. In conclusion, a dose of 100 micrograms fenoterol/40 micrograms ipratropium bromide inhaled from a MDI containing HFA134a propellant is safe and provides effective bronchodilatation of equivalent degree, onset and duration of action to the same dose from the conventional CFC formulation.

Adult↗
PubMed1983

A comparison between the combination emepronium bromide/flavoxate and emepronium bromide in the treatment of detrusor instability.

Emepronium bromide and flavoxate have both and separately been used with success in the treatment of detrusor instability. In this study we have combined the two drugs emepronium bromide and flavoxate and compared the results with emepronium bromide. 20 consecutive patients with an uninhibited bladder, 12 men and 8 women, were randomly allocated to treatment with either emepronium bromide/flavoxate or emepronium bromide. In this trial we found that treatment with the combination is significantly better than treatment with emepronium bromide only.

Adult↗
PubMed2000

The effects of oxitropium bromide on exercise performance in patients with stable chronic obstructive pulmonary disease. A comparison of three different exercise tests.

The purpose of the present study was to compare the characteristics of three different exercise tests in evaluating the effects of oxitropium bromide on exercise performance. Thirty-eight males with stable chronic obstructive pulmonary disease (COPD) (FEV(1) = 40.8 +/- 16.5% predicted; mean +/- SD) completed randomized, double-blind, placebo-controlled, crossover studies for each exercise test. The exercise tests were performed 60 min after the inhalation of either oxitropium bromide 400 microg or placebo. The patients performed 6-min walking tests (6MWT) on Days 1 and 2, progressive cycle ergometry (PCE) on Days 3 and 4, and cycle endurance tests at 80% of the maximal workload of PCE on Days 5 and 6. Spirometry was conducted before and at 45 and 90 min after the inhalation. Oxitropium bromide significantly increased FEV(1) as compared with placebo. Oxitropium bromide increased the endurance time significantly, by 19% (p < 0.001), and caused a small but significant increase in the 6-min walking distance by 1% (p < 0.05), but induced no significant increase in maximal oxygen consumption (V O(2)max) in PCE. The responses in these three exercise tests were different, and we conclude that the endurance test was the most sensitive in detecting the effects of inhaled anticholinergic agents on exercise performance in patients with stable COPD. An endurance procedure may be performed to detect clinical changes in evaluating the effects of oxitropium bromide on exercise performance.

Administration, Inhalation↗
PubMed1995

Propantheline bromide in the management of hyperhidrosis associated with spinal cord injury.

OBJECTIVE: To report 2 cases in which oral propantheline reduced the discomfort associated with sweating related to spinal cord injury (SCI), and to review the literature on the management of SCI-related sweating. CASE SUMMARIES: Case 1: A 27-year-old quadriplegic man with an American Spinal Injury Association (ASIA) Frankel class C injury to C5/C6 experienced profuse sweating and requested propantheline. He stated that he had received the medication previously and reported that propantheline 15 mg tid had controlled his sweating. Propantheline bromide was reinstituted, and within 24 hours, the patient's episodes of profuse sweating had decreased markedly in number and frequency. Case 2: A 35-year-old quadriplegic woman had an ASIA class D lesion at C3. Since her injury, she had experienced profuse sweating that worsened when she became cold and at night. She stated that her sweating was under control as long as she took propantheline. Propantheline therapy was continued and no further sweating episodes have occurred. DATA SOURCE: A MEDLINE search was used to identify pertinent literature including reviews. Standard texts and texts referenced in the pertinent literature also were examined. STUDY SELECTION: All available sources of information were reviewed. DATA SYNTHESIS: The earliest case reports of systemic therapy for hyperhidrosis described the use of the anticholinergic methantheline bromide. Methantheline in combination with ergoloid mesylates also was suggested for the treatment of congenital hyperhidrosis. Local topical therapy for hyperhidrosis, such as aluminum chlorohydrate and aluminum chloride, the active ingredients in some antiperspirants, have been tried with some success. Talc, starch, and other powders have been suggested to absorb excessive sweat. Formalin and glutaraldehyde also have been used. Topical propantheline bromide has been used successfully in treating palmar and plantar hidrosis. Clonazepam has been used successfully in a case of unilateral localized hyperhidrosis. Systemic phenoxybenzamine has been used with some success and there have been attempt at other systemic therapy using mecamylamine, atropine, propoxyphenel, and methenamine. Scopolamine patches also have been used successfully in a small number of patients. Other agents that have been used include dibenamine, piperoxan, and phentolamine. Systemic propantheline also has been listed as an agent with potential efficacy in treating the profuse sweating associated with SCI, but was not recommended primarily because of adverse effects and difficulty in titrating to the lowest effective dosage. However, studies or case reports specific to the use of propantheline in patients with SCI appear to be lacking, as are reports of direct comparison between propantheline and other agents. DISCUSSION: Concerning the mechanism of action of propantheline bromide for hyperhidrosis, it seems reasonable to attribute its effects to the drug's well-documented anticholinergic/antimuscarinic actions. At dosages used to effectively treat neurogenic bladder, propantheline bromide also should block the muscarinic receptors responsible for sweat gland stimulation. Central nervous system adverse effects should be minimal at usual clinical dosages, as propantheline does not cross the blood-brain barrier. CONCLUSIONS: It would appear that in some patients with SCI who are subject to incidental episodes of profuse sweating, oral propantheline may offer some relief and may, in fact, be well tolerated, as in the cases described. Additionally, propantheline would seem a good therapeutic choice in SCI patients with excessive sweating and neurogenic bladder dysfunction who may derive dual benefit from the agent.

Adult↗
PubMed2004

p-Bromophenacyl bromide prevents cumene hydroperoxide-induced mitochondrial permeability transition by inhibiting pyridine nucleotide oxidation.

Mitochondrial permeability transition is commonly characterized as a Ca2+ -dependent non-specific increase in inner membrane permeability that results in swelling of mitochondria and their de-energization. In the present study, the effect of different inhibitors of phospholipase A2--p-bromophenacyl bromide, dibucaine, and aristolochic acid--on hydroperoxide-induced permeability transitions in rat liver mitochondria was tested. p-Bromophenacyl bromide completely prevented the hydroperoxide-induced mitochondrial permeability transition while the effects of dibucaine or aristolochic acid were negligible. Organic hydroperoxides added to mitochondria undergo reduction to corresponding alcohols by mitochondrial glutathione peroxidase. This reduction occurs at the expense of GSH which, in turn, can be reduced by glutathione reductase via oxidation of mitochondrial pyridine nucleotides. The latter is considered a prerequisite step for mitochondrial permeability transition. Among all the inhibitors tested, only p-bromophenacyl bromide completely prevented hydroperoxide-induced oxidation of mitochondrial pyridine nucleotides. Interestingly, p-bromophenacyl bromide had no affect on mitochondrial glutathione peroxidase, but reacted with mitochondrial glutathione that prevented pyridine nucleotides from being oxidized. Our data suggest that p-bromophenacyl bromide prevents hydroperoxide-induced deterioration of mitochondria via interaction with glutathione rather than through inhibition of phospholipase A2.

Acetophenones↗
PubMed1988

Electrophysiological study of intravenous pinaverium bromide in cardiology.

Pinaverium bromide is a musculotropic spasmolytic agent which acts by inhibiting transmembrane calcium movements, an effect similar to that of verapamil. Because of this, an investigation was carried out to see if it had any electrophysiological effects in patients with various cardiac disorders. In an open study, 10 patients received 2 mg pinaverium bromide intravenously. In a double-blind study, 10 patients received 4 mg pinaverium bromide intravenously and 10 patients placebo. Patients included those with either normal or pathological basal conduction, such as bundle-branch block and 1st degree atrioventricular block. Measurements were made of electrophysiological parameters before and 10 minutes after injection. The results showed that neither of the two doses of pinaverium bromide had any effect on atrial excitability, sino-atrial conduction, node and trunk atrioventricular conduction or on intraventricular conduction. No significant difference was seen in comparison with placebo. Pinaverium bromide had no anti-arrhythmic properties in these studies. Local, cardiac and general clinical tolerability was good in all patients.

Aged↗
PubMed1989

[Effects of flutropium bromide, a new antiasthma drug, with repeated administration on bronchomotor response and hepatic drug metabolizing enzymes].

Effects of flutropium bromide, a new antiasthma drug possessing the quarternary ammonium structure of atropine derivatives, were investigated on the bronchodilatory activity with repeated inhalations in guinea pigs and on the hepatic drug metabolizing enzyme activities with repeated i.v. administration in rats. Single inhalation of flutropium bromide (0.03%) inhibited the ACh-induced bronchoconstriction without changing the fall in blood pressure induced by ACh. Flutropium bromide (0.03%) was inhaled for 5 min a day by placing the animal in an inhalation box, successively during periods of 14 and 28 days. The bronchodilatory effect of flutropium bromide after 14- or 28-day repeated inhalations was almost the same potency as that after single inhalation. Twenty-eight-day repeated inhalations did not change the body weight curve in guinea pigs; and in addition, 14-day repeated i.v. administration did not change the hepatic drug metabolizing enzyme activities in rats. From the above results, it is indicated that flutropium bromide causes neither reduction in response nor cumulative effect after repeated inhalations, and that the agent maintains the bronchodilatory effect without change in the hepatic drug metabolizing enzyme activities.

Acetylcholine↗