Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-methylnaltrexone bromide (methylnaltrexone) is a quaternary opioid antagonist with a limited ability to cross the blood-brain barrier. In animal models it reverses at peripheral receptors such side effects of opioids as decreased gastrointestinal motility, emesis, and cough suppression without affecting the desired analgesic effect mediated by central nervous system receptors. Methylnaltrexone thus may be a clinically useful compound for the prevention and treatment of opioid-induced side effects. This study was designed to examine the safety and tolerance of methylnaltrexone in healthy human participants over a range of doses and to identify any adverse effects or toxicity associated with methylnaltrexone and the doses at which these adverse effects occur. Healthy male volunteers received intravenous methylnaltrexone in six ascending doses with a placebo randomly inserted into the sequence. Each participant was observed for subjective and hemodynamic changes. Electrocardiogram and laboratory studies were also performed. The dose-limiting adverse effect of methylnaltrexone was orthostatic hypotension at 0.64 mg/kg (n = 3) or 1.25 mg/kg (n = 5), which was transient and self-limiting. Plasma levels of methylnaltrexone in excess of 1,400 ng/mL were observed to be associated with orthostatic hypotension. There were no significant subjective changes, no release of histamine, and no changes in physical examination or laboratory studies during the course of the study. Pharmacokinetic analysis revealed an elimination half-life of 117.5 minutes (+/-53.2), and a clearance of 38.8 L/hr (+/-17.4) with a methylnaltrexone dose of 0.64 mg/kg. Our results indicate that methylnaltrexone is well tolerated at doses of 0.32 mg/kg in healthy humans.
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PMID:Safety and tolerance of methylnaltrexone in healthy humans: a randomized, placebo-controlled, intravenous, ascending-dose, pharmacokinetic study. 904 69

Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of diseases characterized by cough, sputum production, dyspnoea, airflow limitation and bronchial hyperreactivity. The airflow limitation declines progressively and is irreversible or partially reversible. Bronchodilator therapy is prescribed to relieve the symptoms, reverse airway obstruction and hopefully slow the rate of disease progression and decelerate the decline in pulmonary function. During acute exacerbation, inhalation of beta2-agonists remain the therapy of choice. The usefulness of anticholinergic inhalation in acute attacks is investigated in order to determine if a higher dose and more frequent administration have same benefit as beta2-agonists inhalation. Theophylline is usually given orally as a sustained release formulation for chronic maintenance therapy. Some patients may benefit from theophylline infusion during an acute phase when appropriately used; however, sympathomimetic agents fail to produce adequate bronchodilation. During interim periods of stability, inhalation of ipratropium bromide has increased in popularity as a regular long-term bronchodilator therapy. Although ipratropium and beta2-agonists are equally efficacious when the dosage is adequate enough, a combination of both provides a rapid onset of action of the adrenergic agents and a prolonged action of the anticholinergic. Furthermore, this combination can be given in a reduced dose, thereby avoiding side-effects. Inhalation techniques can influence the efficacy of bronchodilator therapy. For severe dyspnoeic patients or patients with poor technique of co-ordination with metered-dose inhaler (MDI), attachment of a spacer to the MDI or using a nebulizer will overcome these difficulties. Bronchodilator therapy can not prevent the development of COPD or slow down the decline of pulmonary function, other interventions should be included in a comprehensive management programme.
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PMID:Bronchodilator therapy for chronic obstructive pulmonary disease. 952 4

Chronic bronchitis is a clinical diagnosis characterized by a cough productive of sputum for over three months' duration during two consecutive years and the presence of airflow obstruction. Pulmonary function testing aids in the diagnosis of chronic bronchitis by documenting the extent of reversibility of airflow obstruction. A better understanding of the role of inflammatory mediators in chronic bronchitis has led to greater emphasis on management of airway inflammation and relief of bronchospasm. Inhaled ipratropium bromide and sympathomimetic agents are the current mainstays of management. While theophylline has long been an important therapy, its use is limited by a narrow therapeutic range and interaction with other agents. Oral steroid therapy should be reserved for use in patients with demonstrated improvement in airflow not achievable with inhaled agents. Antibiotics play a role in acute exacerbations but have been shown to lead to only modest airflow improvement. Strengthening of the respiratory muscles, smoking cessation, supplemental oxygen, hydration and nutritional support also play key roles in long-term management of chronic bronchitis.
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PMID:Chronic bronchitis: primary care management. 961 9

Mucociliary clearance (MCC), the process in which airway mucus together with substances trapped within are moved out of the lungs, is an important defence mechanism of the human body. Drugs may alter this process, such that it is necessary to know the effect of the drugs on MCC. Indeed, agents stimulating MCC may be used therapeutically in respiratory medicine, especially in patients suspected of having an impairment of their mucociliary transport system. In contrast, caution should be taken with drugs depressing MCC as an undesired side-effect, independently of their therapeutic indication. Since cough clearance (CC) serves as a back-up system when MCC fails, the influence of drugs must be examined not only on MCC but also on CC. Ultimately, the clinical repercussions of alterations in mucus transport induced by drug administration must be studied. Tertiary ammonium compounds (anticholinergics), aspirin, anaesthetic agents and benzodiazepines have been shown to be capable of depressing the mucociliary transport system. Cholinergics, methylxanthines, sodium cromoglycate, hypertonic saline, saline as well as water aerosol have been shown to increase MCC. Adrenergic antagonists, guaifenesin, S-carboxymethylcysteine, sodium 2-mercapto-ethane sulphonate and frusemide have been reported not to alter the mucociliary transport significantly. Amiloride, uridine 5'-triphosphate (UTP), quaternary ammonium compounds (anticholinergics), adrenergic agonists, corticosteroids, recombinant human deoxyribonuclease (rhDNase), N-acetylcysteine, bromhexine and ambroxol have been reported either not to change or to augment MCC. Indirect data suggest that surfactant as well as antibiotics may improve the mucociliary transport system. As for the influence of drugs on CC, amiloride and rhDNase have been demonstrated to increase the effectiveness of cough. A trend towards an improved CC was noted after treatment with adrenergic agonists. The anticholinergic agent ipratropium bromide, which is a quaternary ammonium compound, has been suggested to decrease CC significantly. Bromhexine, ambroxol and neutral saline seemed not to alter CC, either positively or negatively. Finally, treatment with either amiloride, recombinant human deoxyribonuclease, bromhexine, ambroxol, N-acetylcysteine, S-carboxymethylcysteine or hypertonic saline has been suggested as a possible cause of clinical improvement in patients, such as the experience of dyspnoea, the case of expectoration or the frequency of infective exacerbations. Other agents did not show a clinical benefit.
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PMID:Effects of drugs on mucus clearance. 1051 29

The objective of this study was to compare the long-term safety of a fixed combination of fenoterol hydrobromide (50 microg) and ipratropium bromide (20 microg) delivered using a metered dose inhaler (MDI) formulated with a non-chlorinated propellant, hydrofluoroalkanel34a (HFA-MDI), with delivery using the conventional chlorofluorocarbon propellant (CFC-MDI, Berodual/Bronchodual). The study was designed according to Safety Assessment of Marketed Medicines (SAMM) guidelines, to reflect as far as possible the use of MDls under normal prescribing conditions. Two thousand and twenty-seven patients with chronic airways obstruction (CAO) were enrolled from 99 centres in France, 95 centres in Germany and 24 centres in Italy. Following a 2-week run-in period, patients were randomized on a 2:1 basis (1,348 patients to HFA-MDI, 679 patients to CFC-MDI) to receive a flexible dose regimen of the combination (2 puffs, 2-4 times a day, as prescribed by the investigator) during a 12-week open label phase. The overall incidence of adverse events was comparable between both groups. In addition, the incidence of respiratory side effects was also similar, with CAO exacerbations or bronchitis the most frequently recorded events. The safety profile of the HFA formulation was comparable to those of the marketed CFC-MDIs used in Germany and France/Italy. No clinically significant differences were detected between HFA134a or CFC driven inhalers on the switch from CFC- to HFA-MDI (2 weeks before randomisation versus 2 weeks after randomization). There was a trend for taste complaints to be reported more frequently by patients in the HFA-MDI group (0.7% before randomization versus 3.4% after randomization). This, however, was an expected finding as the HFA134a formulation does have a different taste to the CFC formulation. No difference between formulations was observed in the incidences of coughing or paradoxical bronchospasm. The incidence of falls in FEV1 >15% within 15 min following inhalation at each of the clinic visits was 1.2% for both CFC- and HFA-MDIs. In conclusion, administration of a fenoterol/ipratropium bromide combination via hydrofluoroalkane-metered dose inhaler is as safe as delivery by the currently available chlorofluorocarbon-metered dose inhaler, in an extended population of patients with CAO under normal prescribing conditions.
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PMID:Comparison of the safety of drug delivery via HFA- and CFC-metered dose inhalers in CAO. 1078 Jul 56

We compare the efficacy including spirometry, peak expiratory flow (PEFR) and quality of life and safety of an 8-week treatment with inhaled oxitropium, theophylline or their combination in patients with mild-to-severe chronic obstructive pulmonary disease (COPD). We conducted a multicentre, double-blind, double-dummy randomized, parallel-group study at 29 Italian outpatients clinics. A group of 236 patients with mild-to-severe COPD (baseline FEV1 < or = 70% of predicted value) were recruited. Treatments were as follows: Inhaled oxitropium bromide 200 microg (N=75), sustained-release oral theophylline 300 mg (N=81) or their combination (N=80), taken twice daily. Spirometry (FEV1 and FVC) was evaluated every 4 weeks, and morning and evening PEFR (before and 2-4 h after drug intake) was measured daily. Symptoms, cough and dysponea, were recorded daily. Health status was evaluated at baseline and week 8 using the disease specific St George' Respiratory Questionnaire (SGRQ). Any adverse event occurring during the treatment period was recorded on a diary card. FEV1 and FVC improved in all the groups at 4 and 8 weeks, but the difference between treatment groups did not reach statistically significant levels. Differences between groups in pre-dosing morning and evening PEFR were not significant. Post-dosing morning and evening PEFR were increased and the largest increase was seen in patients treated with both drugs. However, differences between groups was significant only for evening values (P=0.008). The proportion of patients who experienced a decrease in symptoms was high in all groups but no differences among groups were observed. SGRQ total scores decreased in all treatment groups after 8 weeks, particularly in the oxitropium and combination groups. Clinically significant change (> or = 4 units) was only observed in patients treated with oxitropium bromide whether with or without theophylline. Adverse events related to treatments were higher in the group treated with theophylline alone (P < 0.02). We conclude that inhaled oxitropium bromide alone was associated with an improvement in FEV1, PEFR and symptoms in patients with COPD that was not statistically different from that of oral theophylline alone or of the combination of both drugs. Oxitropium bromide in combination with theophylline provided a greater improvement in evening post-dosing PEFR. Oxitropium bromide alone or in combination with theophylline improved the quality of life better than theophylline alone.
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PMID:Efficacy and safety of oxitropium bromide, theophylline and their combination in COPD patients: a double-blind, randomized, multicentre study (BREATH Trial). 1241 85

Asthma is a common cause of morbidity and mortality in the United States, with over two million Emergency Department (ED) visits each year. Airway inflammation is recognized as a major component in the pathophysiology of asthma. The classic presentation of asthma is that of wheezing, cough, and dyspnea, however, the severity of airflow limitation correlates poorly with clinical signs. Forced exhaled volume in 1 s (FEV(1)) and the peak expiratory flow rate (PEFR) are direct reflections of the severity of airflow obstruction and are the standard measures used in the ED to assess the severity of airflow obstruction and the response to therapy. Beta2-adrenergic bronchodilators, ipratropium bromide, and corticosteroids form the cornerstone of therapy. Inhaled corticosteroids, leukotriene modifying drugs, and noninvasive positive pressure ventilation should be considered in patients with severe disease and in those who have responded poorly to standard therapy. Mechanical ventilation is usually well tolerated and may be lifesaving in patients with refractory asthma. Precautions are required to prevent dynamic hyperinflation during assisted ventilation.
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PMID:The management of acute severe asthma. 1242 17

Viozan, (Sibenadet HCl, AR-C68397AA) is a dual D2 dopamine receptor, beta2-adrenoceptor agonist that combines bronchodilator activity with the sensory afferent modulating effects associated with D2-receptor agonism. Investigation in animal models of key chronic obstructive pulmonary disease (COPD) symptoms has demonstrated that sibenadet effectively inhibits sensory nerve activity, thereby reducing reflex cough, mucus production and tachypnoea. The results of the early clinical evaluation of this novel agent are reported. An initial proof of concept study (Study 1) aimed to determine the clinical potential of this novel agent by assessing the effects of three doses of sibenadet therapy relative to placebo, with two commonly used bronchodilators, intended to provide a benchmark against which sibenadet activity could be judged. In all, 701 patients were randomized to one of three sibenadet dose groups (400, 600 or 1000 microg ex valve), salbutamol 200 microg, ipratropium bromide (IB) 40 microg or placebo, all three times daily via pressurized metered dose inhaler (pMDI) for 4 weeks. Once the results of Study 1 had been evaluated, a dose-ranging, study (Study 2) involving 872 patients randomized to receive sibenadet (45, 270, or 495 microg ex actuator), or placebo all three times daily via pMDI, for 6 weeks commenced. Both studies were preceded by a 2-week baseline phase and followed by a 2-week follow up period.The primary efficacy variable identified changes in key COPD symptoms over the treatment period (compared with baseline data) as determined by the novel Breathlessness, Cough and Sputum Scale (BCSS). In addition, data on lung function, health-related quality of life and adverse events were collected. Patients receiving sibenadet therapy three times daily exhibited statistically significantly greater improvements in BCSS total score than those receiving placebo or bronchodilator therapy alone. A clear dose-response was evident in Study 2. Symptom improvement in this study was also accompanied by improved lung function and health-related quality of life. Sibenadet therapy was well tolerated with an adverse events profile comparable to current bronchodilator therapy. These data were viewed as extremely encouraging, warranting further, large-scale clinical investigation.
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PMID:Early clinical investigation of Viozan (sibenadet HCl), a novel D2 dopamine receptor, beta2-adrenoceptor agonist for the treatment of chronic obstructive pulmonary disease symptoms. 1256 7

We report resistance to vecuronium bromide (Vb) induced muscle relaxation for general anesthesia in a patient with chronic renal failure (CRF) and secondary hyperparathyroidism (HPT). An 81-year-old man (body weight : 52 kg) diagnosed with bladder carcinoma was scheduled for a total cystectomy. In the operating room, standard monitors were applied except for a nerve stimulator. After epidural catheter had been secured, anesthesia was induced with propofol 80 mg and Vb 5 mg. In spite of administration of these drugs and supplying 5% sevoflurane for 4 minutes, spontaneous respiration was observed. Then, propofol 50 mg and Vb 3 mg were added and lidocaine aerosol 8% was sprayed topically to oropharyngolaryngeal structures. No movement of the vocal cord was observed through the laryngoscope and the patient was intubated smoothly, but the patient did cough and move a little. The surgery was concluded uneventfully. Although the total amount of Vb administration was 14 mg in 3 hr anesthesia time, he was awake rapidly and extubated sooner than expected. We suspect that resistance to Vb has been caused in part by secondary HPT and it appears necessary to take care when administering Vb in CRF patients with secondary HPT, especially at the induction of general anesthesia.
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PMID:[Resistance to vecuronium bromide induced muscle relaxation in a patient with chronic renal failure and secondary hyperparathyroidism]. 1787 55

Intractable asthma is a challenging clinical problem. This study was conducted to determine whether a subset of patients with Intractable asthma may be misdiagnosed and have a form of bronchiolitis instead and also to determine the effectiveness of macrolide therapy in these patients. Seventy six patients with Intractable asthma were re-treated with recommended maximal doses of oral prednisolone for 5 days, beclomethasone, cromolyn sodium, salbutamol and ipratropium bromide for 30 days. Thirty five patients were considered as unresponsive and constituted the study group. They underwent high-resolution CT (HRCT) scan following which they were offered with video-assisted thoracoscopic surgical biopsy. Group 1 (n= 27) refused biopsy and each was treated with macrolide therapy, while Group 2 (n=8) underwent biopsy, and then received macrolide therapy. The patients were treated and followed for three months. The study group consisted of 27 patients, with a mean age of 46.9 +/- 11.1 years. The mean duration of time between the onset of symptoms and the start of this study was 8.1 years. In group 2, no patient had pathologic findings of asthma, and 7/8 had a form of bronchiolitis. There was significant improvement in dyspnea, cough and pulmonary function indices at the end of the 3-month in both groups (p< 0.001). Our results suggest that patients with Intractable asthma could be misdiagnosed and some of them have some forms of chronic bronchiolitis. We believe that any patient who does not respond to standard treatments for Intractable asthma should be evaluated with expiratory HRCT; those with significant air trapping should be considered for a course of macrolide therapy or biopsy for better identification of the underlying disease.
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PMID:Clinical differentiation between resistant asthma and chronic bronchiolitis: testing a practical approach. 1809 44


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