Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new atrovent research articles will be listed here shortly after becoming available to us.
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J Asthma. 2008 Jun; 45(5): 397-401
Bruno S, Antonio C, Roberta B, Clemente F
The protective effect of inhaled anticholinergic drugs in the methacholine-induced bronchospasm is well-known. The objective of this study was to assess if any possible differences may be found among Ipratropium (IB), Oxitropium (OXI) and Tiotropium (TIO) pre-treatments to obtain the protective effect. Forty-four patients with intermittent bronchial asthma and PD(20)FEV(1) < 200 microg were selected (24 M, 20 F; mean age 32 +/- 8.8). On the baseline, they had mean FEV(1)%: 98.8 +/- 8.54 of theoretical and mean PD(15)FEV(1) 111.8 +/- 61.04 microg. After 72 hours, all patients underwent a second methacholine challenge and were given Ipratropium (40 microg by MDI in 14 pts) or Oxitropium (200 microg by MDI in 14 pts) or Tiotropium (18 microg by Handihaler in 16 pts) sixty minutes before the test. Sixty minutes after the bronchodilator inhalation, the FEV(1)% increase was higher (p < 0.05) in OXI (6.7 +/- 4.83%) and TIO groups (6.11 +/- 2.54%) than in the IB group (3.8 +/- 1.96%). In the IB group PD(15)FEV(1) and PD(20)FEV(1) were obtained in all patients, while in the OXI group they were obtained in 12 and 5 pts respectively and in the TIO group in 14 and 5 pts respectively. Normal hyperreactivity was obtained in 2 patients, in both OXI and TIO groups. In OXI and TIO, the PD(15) obtained after drug pre-medication, was similar (respectively 1628 +/- 955.7 and 1595.5 +/- 990 microg), but higher (p < 0.0001) in comparison to the PD(15) measured in the IB group (532.2 +/- 434.8 microg). Also, the dose-response slope (decline percentage of FEV(1)/cumulative methacholine dose) after PD(15) was similar in both OXI and TIO groups but different in the IB group. A significant relationship (p < 0.01) was found between PD(15)FEV(1) (obtained in 40 pts) and the increase in FEV(1)% obtained 60 minutes after bronchodilator inhalations (r = 0.53). In conclusion, with a standard dose, both Oxitropium and Tiotropium seem to have the same protective effect in bronchial asthma but higher than Ipratropium. It's probable that the best dose of Ipratropium should be a higher one than the usual dose taken.
Rate and Characteristics of Asthma Exacerbations: The ASMAB I Study.
Arch Bronconeumol. 2008 Jun; 44(6): 303-311
Morell F, Genover T, Muñoz X, García-Aymerich J, Ferrer J, Cruz MJ
OBJECTIVE: The aim of this study was to determine the incidence and clinical characteristics of asthma exacerbations seen by emergency services in Barcelona, Spain (the ASMAB-I study). PATIENTS AND METHODS: The emergency services considered in the study served a population of 1 203 598 inhabitants aged over 14 years. Episodes treated in hospital emergency departments and by emergency services called to patients' homes over a period of 129 days were included in the study. RESULTS: In total, 831 episodes of exacerbation were identified; 523 were seen in 3 university hospitals, 113 in secondary hospitals, and 195 by emergency services at the patient's home. Twenty of the patients seen at home were subsequently taken to hospital. The mean frequency was 6.4 episodes per day, corresponding to a daily incidence of 0.53 exacerbations per 100 000 inhabitants (95% confidence interval, 0.46-0.56 exacerbations/100 000 inhabitants) and 8.2 per 100 000 asthmatic patients (95% confidence interval, 6.89-8.41 exacerbations/100 000 asthmatic patients). Of the 276 episodes treated between Monday and Thursday in university hospitals, 66 patients (24%) reported acute onset and 14 (5%) sudden onset. Only 85 patients (31%) regularly used inhaled corticosteroids and only 33 (12%) added oral corticosteroids in the 12 hours prior to consulting emergency services. In 16% of cases the episode was classified as severe and in 3% near fatal. Eighty-two patients (30%) were ultimately admitted to hospital: 12% of mild exacerbations, 39% of moderate exacerbations, 62% of severe episodes, and 100% of near-fatal episodes. The Charlson comorbidity index was higher in patients admitted to hospital (P< .001). In the 28 patients readmitted to hospital (10%), antibiotics (P< .001) and ipratropium bromide (P< .0001) had been prescribed less often at the time of discharge after the first hospital admission. CONCLUSIONS: The rate of asthma exacerbation established in this study may be a useful indicator of the degree of control of the disease and may serve as a reference to confirm future short-term or lasting increases in asthma exacerbation. Rapid onset (acute or sudden) is common and many patients are not receiving appropriate treatment prior to hospital admission. Severe exacerbation is common in our practice setting. Hospital admission is related to severity and comorbidity. Patients who are readmitted to hospital had less often received antibiotic treatment and ipratropium bromide when discharged previously.
Pulm Pharmacol Ther. 2008 May 1;
Bleecker ER, Emmett A, Crater G, Knobil K, Kalberg C
This retrospective analysis of data from two multi-center, randomized, double-blind, parallel group studies compared the efficacy of fluticasone propionate/salmeterol (FSC) 250/50mcg twice daily with ipratropium bromide/albuterol (IB/ALB) 36/206 mcg four times daily in albuterol-reversible (n=320 [44%]) and non-reversible (n=399 [56%]) patients with COPD. In reversible and non-reversible patients, both treatments significantly increased FEV(1)AUC(0-6h) from baseline and the magnitude of improvement was larger in reversible patients. FSC increased FEV(1)AUC(0-6h) by 1.46+/-0.08 and 1.98+/-0.13 l-h at Day 1 and Week 8, respectively, in reversible patients, compared with 0.71+/-0.06 and 0.94+/-0.10 l-h in non-reversible patients (p
Alteration in prehospital drug concentration after thermal exposure.
Am J Emerg Med. 2008 Jun; 26(5): 566-73
Gammon DL, Su S, Jordan J, Patterson R, Finley PJ, Lowe C, Huckfeldt R
OBJECTIVE: The aim of the study was to determine the remaining concentration of 23 commonly carried emergency medical services medications used in the United States after they have experienced thermal extremes that have been documented in the prehospital environment for a period of 1 month. METHODS: Pharmaceuticals were thermally cycled (-6 degrees C and 54 degrees C) every 12 hours and then assayed by high-performance liquid chromatography. RESULTS: Eight (35%) of 23 prehospital pharmaceuticals revealed ending concentrations of less than 90% with strong correlation to thermal exposure time. These included lidocaine, diltiazem, dopamine, nitroglycerin, ipratropium, succinylcholine, haloperidol, and naloxone. CONCLUSION: A decrease in concentration was found to be statistically significant in 8 (35%) of 23 commonly carried emergency medical services pharmaceuticals. These results provide new information and perspective regarding stability of emergency drugs in the prehospital environment by evaluating a broad range of pharmaceuticals as well as by using thermal exposure points that have been documented in the United States.
J Cardiopulm Rehabil Prev. 2008 May-Jun; 28(3): 208-14
Deschênes D, Pepin V, Saey D, LeBlanc P, Maltais F
PURPOSE: To evaluate the concordance between subjective and objective indices of muscle fatigue during exercise and to assess the significance of the perception of dyspnea and leg fatigue for the exercise response to bronchodilation in chronic obstructive pulmonary disease (COPD). METHODS: Sixty-eight patients with COPD performed either 2 constant work-rate cycling exercises or 2 endurance shuttle walking tests. These tests were preceded by nebulization of placebo or 500 mug of ipratropium bromide. Changes in forced expiratory volume in 1 second and in endurance time with bronchodilation were measured. Changes in quadriceps twitch force after exercise were evaluated. In addition, the locus of symptom limitation was assessed. RESULTS: Patients who stopped exercising because of leg fatigue showed a larger fall in quadriceps twitch force in comparison with patients who stopped for dyspnea. The proportion of patients who developed contractile fatigue of the quadriceps (postexercise fall in quadriceps twitch force >15% resting value) was substantially smaller in patients stopping exercise because of dyspnea than in those stopping because of leg fatigue or a combination of the 2 symptoms. The locus of symptom limitation modulated the exercise response to bronchodilation; patients stopping exercise because of leg fatigue or a combination of dyspnea/leg fatigue showed a smaller improvement in endurance time to constant work-rate exercise with bronchodilation compared with those stopping because of dyspnea. CONCLUSION: Patients with COPD reporting leg fatigue as the main exercise-limiting symptom had a smaller increase in endurance time to constant work-rate exercise after bronchodilation compared with those reporting dyspnea as the main limiting symptom.
Cardiovascular morbidity and the use of inhaled bronchodilators.
Int J Chron Obstruct Pulmon Dis. 2008; 3(1): 163-9
Macie C, Wooldrage K, Manfreda J, Anthonisen N
We used the Manitoba Health database to examine the relationship between use of inhaled respiratory drugs in people with chronic obstructive respiratory diseases and cardiovascular hospitalizations from 1996 through 2000. The drugs examined were beta agonists [BA], ipratropium bromide IB, and inhaled steroids (ICS). End points were first hospitalizations for supraventricular tachycardia, myocardial infarction, heart failure or stroke. A nested case control analysis was employed comparing people with and without cardiovascular events. Cases and controls were matched for gender and age, and conditional logistic regression was used in multivariate analysis considering other respiratory drugs, respiratory diagnosis and visit frequency, non-respiratory, non-cardiac comorbidities, and receipt of drugs for cardiovascular disease. In univariate analyses, BA, IB and ICS were all associated with hospitalizations for cardiovascular disease, but in multivariate analyses ICS did not increase risk while both BA and IB did. There were interactions between respiratory and cardiac drugs receipt in that bronchodilator associated risks were higher in people not taking cardiac drugs; this was especially true for stroke. There were strong interactions with specific cardiac drugs; for example, both BA and IB substantially increased the risk of supraventricular tachycardia in patients not anti-arryhthmic agents, but not in the presence of such agents. We conclude that bronchodilator therapy for chronic obstructive diseases is associated with increased cardiovascular risk, especially in patients without previous cardiovascular diagnoses, and that this is unlikely due to the severity of the respiratory disease, since risk was not increased with ICS.
Drugs Aging. 2008; 25(5): 415-43
Gupta P, O'Mahony MS
Asthma and chronic obstructive pulmonary disease (COPD) are common disorders that are associated with increasing morbidity and mortality in older people. Bronchodilators are used widely in patients with these conditions, but even when used in inhaled form can have systemic as well as local effects. Older people experience more adverse drug effects because of pharmacodynamic and pharmacokinetic changes and particularly drug-drug and drug-disease interactions.Cardiovascular disease is common in older people and beta-adrenoceptor agonists (beta-agonists) have inotropic and chronotropic effects that can increase arrhythmias and cardiomyopathy. They can also worsen or induce myocardial ischaemia and cause electrolyte disturbances that contribute to arrhythmias. Tremor is a well known distressing adverse effect of beta-agonist administration. Long-term beta-agonist use can be associated with tolerance, poor disease control, sudden life-threatening exacerbations and asthma-related deaths. Functional beta(2)-adrenoceptors are present in osteoblasts, and chronic use of beta-agonists has been implicated in osteoporosis.Inhaled anticholinergics are usually well tolerated but may cause dry mouth, which can be troublesome in older people. Pupillary dilatation, blurred vision and acute glaucoma can occur from escape of droplets from loosely fitting nebulizer masks. Although ECG changes have not been seen in randomized controlled trials of long-acting inhaled anticholinergics, supraventricular tachycardias have been observed in a 5-year randomized controlled trial of ipratropium bromide. Paradoxical bronchoconstriction can occur with inhaled anticholinergics as well as with beta-agonists, but tolerance has not been reported with anticholinergics. Anticholinergic drugs also cause central effects, most notably impairment of cognitive function, and these effects have been noted with inhaled agents.Use of theophylline is limited by its adverse effects, which range from commonly occurring gastrointestinal symptoms to palpitations, arrhythmias and reports of myocardial infarction. Seizures have been reported, but are rare. Theophylline is metabolized primarily by the liver, and commonly interacts with other medications. Its concentration in plasma should be monitored closely, especially in older people.Although many clinical trials have been conducted on bronchodilators in obstructive airways disease, the results of these clinical trials need to be interpreted with caution as older people are often under-represented and subjects with co-morbidities actively excluded from these trials.
Rhinology. 2008 Mar; 46(1): 45-51
Sapci T, Yazici S, Evcimik MF, Bozkurt Z, Karavus A, Ugurlu B, Ozkurt E
Idiopathic rhinitis without eosinophilia is a group of frequently observed diseases, the aetiopathogenesis of which is not yet well known. One of the most disturbing symptoms for patients within this disease group is nasal hypersecretion. Although many different treatments have been tried for hypersecretion, nasal topical drugs form the basis of any such therapy today. Ipratropium bromide (IB) is a drug offirst choice in nasal hypersecretion therapy. It displays a parasympatholytic effect in topical use and antagonizes acetylcholine transport in efferent parasympathetic nerves, thus decreasing submucosal gland secretion, which is the cause of hypersecretion. Botulinum toxin type A (BTX-A) is among the alternative treatment choices that is increasingly used in symptomatic treatment of nasal hypersecretion. Our study was planned with the aim of comparing the effect of these two groups of drugs on nasal hypersecretion. Thirty-eight patients who were diagnosed with idiopathic rhinitis without eosinophilia were included in the study and were divided in 3 different groups: In the first group, a total of 10 units of BTX-A were injected into both nasal cavities. In the second group, 3x2 IB was injected into both nasal cavities for 4 weeks. The third group received intranasal physiologic saline as placebo. The patients were evaluated in terms of nasal hypersecretion with visual analogue scale prior to the treatment and at weeks 1, 2, 4, 8, and 12 during the follow-up period. Throughout the 8 weeks follow-up period, the patient complaints displayed a 41.2% decrease in the group that received BTX-A and a 61.4% decrease in the group which received IB, while no change was observed in the control group. Both drug groups were well tolerated by the patients, with no serious adverse or systemic effects. As a result, while IB and BTX-A differ in terms of method of application, they display a similar degree and duration of efficiency in hypersecretion therapy.
Ter Arkh. 2008; 80(3): 10-4
Dotsenko EK, Goncharova VA, Kuzubova NA, Kamenova MIu, Egorova NV
AIM: To study biochemical composition of expired air condensate (EAC) in patients with chronic obstructive pulmonary disease (COPD) in relation to a phase and severity of the disease and its treatment. MATERIAL AND METHODS: EAC was investigated in 18 COPD patients and 9 healthy subjects. Basic broncholytic therapy with ipratropium bromide was combined with beclomethasone and fenspiride in 11 and 7 patients, respectively. The condensate was lyophilised, the residue was solved and analysed on the biochemical analyzer Casis (Beringer Manheim, Rosch). EAC was examined for albumin, C-reactive protein, glucose, cholesterol, triglycerides, urea, uric acid, alkaline phosphatase (AP), lactate dehydrogenase, gamma-glutamyl transferase, total calcium, magnesium. RESULTS: Compared to healthy subjects, COPD patients' EAC contains significantly higher levels of albumin, C-reactive protein, calcium, bilirubin and more active AP. Quantitative composition of EAC depends on COPD phase and severity. A negative correlation exists between FEV+AEA-1 and albumin concentration, FEV+AEA-1 and CRP concentration. The anti-inflammatory therapy decreases EAC content of both protein and lipid metabolism products, enzyme activity reflecting attenuation of oxidant and inflammatory processes, stabilization of cell membranes in the respiratory zone. CONCLUSION: EAC composition reflects metabolic processes in the lungs and can be used for assessment of airway affection, activity of the inflammatory process and COPD treatment efficacy.
Confirmed beta16 Arg/Arg polymorphism in a patient with uncontrolled asthma.
Ann Pharmacother. 2008 Jun; 42(6): 874-81
Metzger NL, Kockler DR, Gravatt LA
OBJECTIVE: To report a case of confirmed beta(16) Arg/Arg polymorphism (Arg/Arg) in a patient with uncontrolled asthma. CASE SUMMARY: A 49-year-old black female presented to the emergency department with acute shortness of breath with subsequent intubation. After extubation, she reported multiple hospitalizations for asthma with one prior intubation, adherence to asthma medications, and very frequent use of her short-acting beta(2)-agonist (SABA). Because of her asthma history, self-reported adherence, and race, she was tested for beta(2)-adrenoreceptor genotype, which revealed Arg/Arg. Based on these findings, beta(2)-agonists were discontinued and tiotropium (maintenance) and ipratropium (primary rescue) were initiated as part of her asthma regimen. Application of the Naranjo probability scale revealed probable causality between uncontrolled asthma in our patient and SABA use. The patient is followed in our outpatient pulmonary clinic and, at time of writing, had not been admitted to our hospital for asthma-related events. DISCUSSION: Approximately 15% of Americans with asthma are Arg/Arg, with an increased prevalence in black and Asian populations. It is hypothesized that changes in the degree of sensitivity or desensitization to the bronchodilator effect of beta(2)-agonists may occur in these individuals. Data exist, although they are conflicting, suggesting that inhaled beta(2)-agonists may worsen clinical outcomes. Trials have reported declines in peak expiratory flow rates plus increases in asthma symptoms and exacerbations when SABAs have been used regularly in patients with Arg/Arg. Studies evaluating long-acting beta(2)-agonists (LABAs) have inconsistent results. Preliminary data suggest that anticholinergics may serve as a beneficial primary rescue medication instead of beta(2)-agonists in patients with Arg/Arg. CONCLUSIONS: Clinicians should be aware of factors (eg, race and polymorphisms) that may predict unfavorable outcomes with regular SABA and possibly LABA use. Patients with poor asthma control despite adherence to asthma therapy may benefit from beta(2)-adrenoreceptor genotyping and, possibly, from anticholinergics.