Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After about half a century of treatment of asthma and chronic obstructive pulmonary disease, theophylline still occupies a central position in the treatment of these conditions. Severe poisonings are rare and may occur as a result of chronic over-medication or acute self-poisoning. The clinical course depends not only on the amount taken and the peak serum concentration, but also on whether the intoxication is acute or chronic. The therapeutic range is narrow (55-110 mumol/l). Total body clearance of theophylline varies considerably between individuals, and drug interactions are common. These circumstances lead to relatively high risk of poisoning. Clinical features vary from moderate gastrointestinal discomfort, particularly nausea, tremor and tachycardia, to life-threatening conditions affecting the cardiovascular and central nervous systems. Treatment is discussed in connection with a presentation of three case histories.
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PMID:[Theophylline poisoning--clinical course and treatment]. 864 49

The objectives of this study were to compare the efficacy and safety of salmeterol xinafoate (50 and 100 microg b.i.d.) with that of placebo, when added to existing therapy, in the treatment of patients with chronic obstructive pulmonary disease (COPD). Six hundred and seventy four patients were randomized to receive either salmeterol 50 microg b.i.d., salmeterol 100 microg b.i.d., or placebo treatment for a period of 16 weeks. The results showed a significant improvement in daily symptom scores noted for patients taking either 50 microg (p=0.043) or 100 microg b.i.d. salmeterol (p=0.01) compared with placebo, with a corresponding decrease in additional daytime salbutamol requirements for both salmeterol groups. The same pattern was reflected for night-time symptoms and additional salbutamol use. During treatment, forced expiratory volume in one second (FEV1) measurements improved significantly in each salmeterol group, with up to a 7% improvement observed at the end of the study. Although no difference was observed between treatment groups for the distance walked in 6 min, patients treated with salmeterol 50 microg b.i.d. were significantly less breathless than those treated with placebo after their 6 min walk, after 8 weeks (p=0.024) and 16 weeks (p=0.004) of therapy. Adverse events were similar in all three groups except for tremor, which was significantly higher in the 100 microg b.i.d. salmeterol group (p=0.005) compared both with 50 microg b.i.d. salmeterol and placebo. Salmeterol offered further positive improvement to the effect of therapy in patients with chronic obstructive pulmonary disease when added to their existing regimens. This clinical improvement was similar both with 50 and 100 microg b.i.d. dosage, although the group receiving 50 microg b.i.d. tolerated the drug better than those receiving 100 microg b.i.d. salmeterol.
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PMID:An evaluation of salmeterol in the treatment of chronic obstructive pulmonary disease (COPD) 915 Mar 18

Selection of beta-adrenergic blockers for formulary addition can be a difficult task, especially with the increasing availability of new beta-blockers, as well as the numerous differences in pharmacodynamic and pharmacokinetic properties of currently available agents. Nevertheless, appropriate evaluation of the important characteristics of beta-blockers should allow selection of the most cost-effective agents for formulary addition. Most importantly, differences in efficacy, product formulation and cost should be carefully considered when making formulary decisions. Notably, evidence from clinical trials indicates differences in efficacy among beta-blockers for post-myocardial infarction prophylaxis, situational anxiety, essential tremor, thyrotoxicosis, migraine prophylaxis and prevention of bleeding associated with oesophageal varices. For many clinical situations, it is also important to select an effective agent that is available in both an oral and intravenous formulation, especially for cardioprotection after acute myocardial infarction and for use in supraventricular arrhythmias. In addition, availability of sustained release products and generic formulations should be considered for their potential to increase compliance and decrease cost, respectively. Comparative drug costs, as well as costs associated with decreased compliance, should also be carefully evaluated. Differences in beta-receptor selectivity, duration of action and presence of intrinsic sympathomimetic activity (ISA) are also important considerations in the selection of beta-blockers for formulary consideration. Although degree of selectivity is relative, beta 1-selective agents may be less likely to induce bronchospasm in patients with chronic obstructive pulmonary disease (COPD) and may be less likely to affect glucose homeostasis in patients with diabetes mellitus. Duration of action of a beta-blocker is an important consideration for evaluation of efficacy throughout the recommended dosage interval. In addition, beta-blockers with a long duration of action can often be administered once or twice daily, potentially leading to increased compliance and thereby improved effectiveness and economic efficiency. The presence of ISA is an important consideration because certain beta-blockers with ISA may be less effective than those without ISA for certain indications. Factors considered to be less important when making formulary decisions of choice of beta-blockers include the route of elimination, lipophilicity and presence of membrane stabilising activity.
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PMID:Formulary considerations in selection of beta-blockers. 1015 Jan 54

The incidence of drug-induced adverse effects is likely to increase as a result of advanced age and exposure of elderly patients to polypharmacy. Therefore, pharmacological therapy of asthma and chronic obstructive pulmonary disease (COPD) in the elderly patient can be potentially hazardous. beta(2)-agonists, administered as therapy for asthma and COPD, have recognised systemic sequelae, such as hypokalaemia and chronotropic effects, which may be life-threatening in susceptible patients. Adverse effects such as hypokalaemia can be aggravated by concomitant treatment with other drugs promoting potassium loss including diuretics, corticosteroids and theophyllines. In addition, relatively minor adverse events associated with the administration of beta(2)-agonists, such as tremor and blood pressure changes, may be of significance to the elderly patient leading to impairment in the quality of life. However, long-term treatment with beta(2)-agonists may reduce the incidence of drug-induced adverse effects as a result of beta-receptor subsensitivity. Oral and inhaled corticosteroids have been used for the treatment of acute asthma and COPD in the elderly patient. Long-term treatment with oral corticosteroids can result in serious systemic adverse effects such as suppressed adrenal function, bone loss, skin thinning and cataract formation. In contrast to beta(2)-agonists, oral corticosteroids can upregulate beta(2)-adrenoceptors and thereby potentiate the systemic sequelae of beta(2)-agonists. Hence, oral corticosteroids should be administered with caution for as short a duration as possible. Inhaled corticosteroids appear to be relatively well tolerated when administered at doses below approximately 1000 microg. However, larger doses of inhaled corticosteroids may affect hypothalamic-pituitary-adrenal function and bone turnover. In the case of inhaled corticosteroids, spacer devices, often used in older patients who cannot operate metered dose inhalers, can potentiate the systemic sequelae of both corticosteroids and beta(2)-agonists. The use of theophyllines in the treatment of COPD or chronic asthma is controversial. Theophyllines have a wide adverse effect profile and are prone to drug-drug interactions. The adverse effects may be mild or life threatening and include nausea and vomiting or sinus and supraventricular tachycardias. Therefore, theophyllines should be prescribed with extreme caution to elderly patients with asthma or COPD. In contrast, inhaled anticholinergic drugs such as ipratropium bromide and oxitropium bromide are generally safe in elderly patients and have useful bronchodilator function. Commonly reported adverse effects are an unpleasant taste and dryness of the mouth. When used as first-line therapy, anticholinergic drugs may optimise the bronchodilator effects of low-dose inhaled beta(2)-agonists in patients with chronic airflow obstruction, and hence obviate the need for higher doses.
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PMID:Asthma medications and their potential adverse effects in the elderly: recommendations for prescribing. 1173 62

Viozan (sibenadet HCl, AR-C68397AA) is a novel dual D2 dopamine receptor, beta2-adrenoceptor agonist that has been investigated for efficacy in alleviating the symptoms of chronic obstructive pulmonary disease (COPD). The slowly progressive nature of this disease means that patients will require ongoing therapeutic management for many years, or even decades. With such long-term treatment, the safety profile of new agents will be of paramount importance. As part of the large-scale assessment of sibenadet, a 12-month safety study has been conducted. Following completion of a 2-week baseline period, 435 adults with stable, symptomatic, smoking-related COPD were randomized to receive either 500 microg sibenadet or placebo delivered via pressurized metered dose inhaler (pMDI), three times daily for 52 weeks. Sibenadet therapy was generally well tolerated, with the only notable differences seen in the incidence of tremor and taste of treatment (16.9% vs. 4.1% and 14.5% vs. 4.1% in the sibenadet and placebo groups respectively). There were a total of 79 patients with serious adverse events (SAEs), 43 (14.8%) in the sibenadet pMDI group and 36 (24.8%) in the placebo group. No clinically significant abnormal laboratory values or overall differences between treatment groups were noted. Similarly, there were no clinically significant differences between the two treatment groups for cardiac variables, or in vital signs. The secondary variables showed no notable differences with respect to lung function, exacerbations or health-related quality of life. Due to the effective beta2-agonist properties, patients in the sibenadet group did, however, report reduced rescue medication usage at all timepoints. While the results of this study show that, overall, sibenadet therapy was well tolerated, the lack of sustained benefit reported in large-scale clinical efficacy studies means that sibenadet development will not be continued.
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PMID:Long-term use of Viozan (sibenadet HCl) in patients with chronic obstructive pulmonary disease: results of a 1-year study. 1256 10

The two inhaled long-acting beta2-adrenoceptor agonists, salmeterol and formoterol, have been studied extensively since their introduction in the early 1990s. In this review we consider the evidence for their efficacy and safety in adults with asthma and chronic obstructive pulmonary disease (COPD), by reviewing long-term prospective studies in which these drugs have been compared with placebo or an alternative bronchodilator. We have also assessed safety, including data from postmarketing surveillance studies and case-control studies using large databases. In patients with asthma, salmeterol and formoterol increase lung function, reduce asthmatic symptoms and improve quality of life when compared with placebo. Both drugs protect against exercise-induced asthma, although some tolerance develops with regular use. Tolerance to the bronchodilator effects of formoterol has also been seen, although this is small and most of the beneficial effects are maintained long-term. Both drugs have been shown to reduce asthma exacerbations but only in studies in which most patients were taking an inhaled corticosteroid. Adding a long-acting beta2-agonist provided better control than increasing the dose of inhaled corticosteroid in several studies. Long-acting beta2-agonists also provide better asthma control than use of regular short-acting beta2-agonists and theophylline. Their relative efficacy compared with leukotriene antagonists is uncertain as yet. Formoterol appears to be at least as safe and effective as a short-acting beta2-agonist when used on an 'as required' basis. In patients with COPD, both salmeterol and formoterol offer improved lung function and reduced COPD symptoms compared with placebo, and quality of life has been improved in some studies. Some tolerance to the bronchodilating effect of salmeterol was seen in one study. Most studies have not found a significant reduction in exacerbations in COPD. Both drugs have provided greater benefit than ipratropium bromide or theophylline; there are limited data on tiotropium bromide. The long-acting beta2-agonists cause predictable adverse effects including headache, tremor, palpitations, muscle cramps and a fall in serum potassium concentration. Salmeterol can also cause paradoxical bronchospasm. There is some evidence that serious adverse events including dysrhythmias and life-threatening asthma episodes can occur; however, the incidence of such events is very low but may be increased in patients not taking an inhaled corticosteroid. Salmeterol 50 microg twice daily and formoterol 12 microg twice daily are effective and safe in treating patients with asthma and COPD. Higher doses cause more adverse effects, although serious adverse events are rare.
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PMID:A benefit-risk assessment of inhaled long-acting beta2-agonists in the management of obstructive pulmonary disease. 1535 Jan 54

Long-acting beta2-agonist (LABA) and inhaled corticosteroid (ICS) combination therapy is recommended by international treatment guidelines for COPD. The current literature concerning the safety of LABAs and ICS, both as monotherapies and in combination, in patients with COPD is reviewed. Bronchodilators such as LABAs are key treatments for COPD due to their effects on bronchial smooth muscle and airflow limitation. LABAs are well-tolerated in patients with COPD, with a low incidence of reported adverse events (AEs). Most AEs associated with LABA use are due to systemic exposure and include muscle tremor and cardiac effects. Placebo-controlled studies in patients with COPD demonstrate that there is no increase in risk of cardiac AEs with LABA therapy. ICS therapy targets airway inflammation in COPD, and is associated with a reduction in the frequency of COPD exacerbations, and improvements in symptoms, lung function and health status. Localized effects such as oropharyngeal irritation are common with ICS, but are not considered to be serious. Potential ocular effects with ICS therapy in patients with COPD have been identified and require further investigation. Rare, but more serious AEs related to ICS use are the effects on bone and the suppression of endogenous cortisol production; however, the clinical relevance of these effects is unclear. Clinical data indicate that LABA/ICS combination therapy is more effective in COPD than either agent used alone and is not associated with any additional AEs.
COPD 2006 Aug
PMID:Clinical safety of long-acting beta2-agonist and inhaled corticosteroid combination therapy in COPD. 1724 Jun 18

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 beta2-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.
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PMID:Potential adverse effects of bronchodilators in the treatment of airways obstruction in older people: recommendations for prescribing. 1844 5

COPD is characterized by progressive airflow obstruction which does not fully reverse to inhaled or oral pharmacotherapy. The management of patients with COPD has taken a totally new direction over the past 20 years, thank to the use of novel therapies aimed to improve and modify the natural history of COPD. Long-acting bronchodilators, including long-acting beta2-agonists (LABAs), were introduced several years ago in order to enhance improvements in lung function, health status related quality of life, and reduce the rate of exacerbations. These effects can be boosted by the combination of LABAs with long-acting anticholinergic, and/or with inhaled corticosteroids. Inhaled LABAs are commonly well tolerated although adverse effects such as tremor and palpitations are occasionally troublesome.
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PMID:Long-acting beta2-agonists (LABA) in chronic obstructive pulmonary disease: efficacy and safety. 1928 Oct 71

The most effective bronchodilators in chronic obstructive pulmonary disease (COPD) are beta(2)-adrenergic and anticholinergic agents. When administered via inhalation and at recommended doses, these drugs are well tolerated and generally safe. beta-Adrenergic agents show systemic effects such as an increase in heart rate, QT prolongation, hypopotassemia and tremor. These effects have little clinical significance. Nevertheless, patients with cardiac comorbidity or respiratory insufficiency can be at greater risk of arrhythmia and other adverse cardiac events. Long action beta(2)-adrenergic agents have not been shown to increase mortality in COPD. The most frequent adverse effect of anticholinergic agents is dryness of the mouth; these drugs also increase the risk of glaucoma and urinary retention. Anticholinergic agents may increase cardiovascular risk, although the evidence is inconsistent. The use of methylxanthines is limited by frequent gastrointestinal adverse effects and by the narrow therapeutic range of these drugs.
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PMID:[Safety and tolerability of bronchodilators in chronic obstructive pulmonary disease]. 2011 58


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