Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Within the last 10 years the indications for a therapeutic regimen with beta-blocking-agents have been differentiated: coronary heart disease with angina pectoris (interval regimen), essential hypertension, especially in younger persons; hyperkinetic heart syndrome; thyreotoxikosis, symptomatic therapy; heart rhythm disorders, extrasystolic or tachysystolic; neurologic-psychiatric diseases. The development of the newer beta-blocking-agents has effected different kinetic data (f.i. long acting effects of Tenormin) and a increased cardioselectivity. The recommendations for the therapeutic regimen have to be outlined to the underlying diseases. The sensitivity against the drugs depends on remarkable individual differences, with the consequence of a careful and low dosage in the beginning in each case. The side-effects of beta-blocking-agents are presumably: bradycardia, bronchospasm, fatigue, adynamia, myocardial insufficiency, gastrointestinal symptoms, hypoglycemia, hypotension.
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PMID:[Therapy with beta-blocking-agents (author's transl)]. 3 43

Conventional formulations of metoprolol have become well established in cardiovascular medicine and are particularly useful in the management of hypertension and ischaemic heart disease. Recently developed controlled release metoprolol delivery systems (metoprolol CR/ZOK and metoprolol OROS) were designed to overcome the drug delivery problems of matrix-based sustained release forms by releasing the drug at a relatively constant rate over a 24-hour period, and thus producing sustained and consistent metoprolol plasma concentrations and beta 1-blockade while retaining the convenience of once daily administration. Clinically and statistically significant reductions in blood pressure have been observed with metoprolol CR/ZOK and metoprolol OROS 24 hours after administration in mildly or moderately hypertensive patients. Studies in patients with mild to moderate hypertension have demonstrated that a similar or higher percentage of patients achieved a goal response with metoprolol CR/ZOK compared with matrix-based sustained release formulations of metoprolol, or conventional atenolol or bisoprolol, while metoprolol OROS achieved an equal or greater response rate compared with conventional or matrix-based sustained release metoprolol preparations. In patients with stable effort angina pectoris, once daily administration of metoprolol CR/ZOK provided at least equal antianginal efficacy as conventional metoprolol in divided doses, while metoprolol OROS reduced the mean number of anginal attacks by the same margin as atenolol. Controlled release metoprolol formulations have been well tolerated in clinical trials. Metoprolol CR/ZOK was associated with a similar or lesser degree of adverse effects related to the central nervous system compared with atenolol or long acting propranolol. Metoprolol CR/ZOK also demonstrated less pronounced beta 2-mediated bronchoconstrictor effects than atenolol in asthmatics, and less general fatigue and leg fatigue in healthy subjects. Metoprolol OROS produced less pronounced bronchoconstrictor effects than atenolol, matrix-based sustained release metoprolol or long acting propranolol in patients with asthma or obstructive airways disease, and healthy volunteers. These results are presumably due to the beta 1-selectivity of metoprolol in addition to the relatively low plasma concentrations maintained by metoprolol CR/ZOK and metoprolol OROS, and the avoidance of high peak plasma concentrations with these agents. Despite the relative safety of the controlled release forms of metoprolol, the use of all beta-adrenoceptor antagonists should be avoided in patients with a history of bronchospasm. Thus, controlled release metoprolol formulations offer the potential to maximise the confirmed benefits of this agent in the management of hypertension and angina, by maintaining clinically effective plasma concentrations within a narrow therapeutic range over a 24-hour dose interval.
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PMID:Controlled release metoprolol formulations. A review of their pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and ischaemic heart disease. 137 20

We have conducted a retrospective survey of 79 children out of a total hospital asthmatic patient population of 2,412, admitted over a 32 month period to the ICU for the management of severe status asthmaticus. All patients were in severe respiratory distress with CO2 retention; 19 required mechanical ventilation due to increasing fatigue and worsening bronchospasm, having failed to respond to either inhaled or IV bronchodilator therapy. All patients were ventilated at slow rates (less than 12 min) and their airway pressure (Paw) was deliberately kept below 45 cmH2O, while accepting a PaCO2 in the 45-60 mmHg range, as long as the pH was compensated. Although two patients developed pneumothoraces while on positive pressure ventilation, these were resolved without incidents. Five patients who had mediastinal or subcutaneous air leaks prior to intubation did not develop pneumothoraces. Following the initiation of mechanical ventilation, IV beta-agonist therapy was increased in order to reverse the bronchospasm and reduce the duration of mechanical ventilation. Mean duration of intubation was 42 hours. Fourteen of the 19 patients were weaned and extubated within 48 hours. All patients survived without sequelae. We conclude that a degree of controlled "hypoventilation" by deliberately choosing Paw less than 45 cmH2O can be successfully used to ventilate children with severe status asthmaticus with a reduced rate of pressure-related complications.
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PMID:Efficacy, results, and complications of mechanical ventilation in children with status asthmaticus. 175 29

beta-receptor antagonists have for many years been considered appropriate alternatives in the primary management of mild to moderate hypertension. Generally, they have been shown to be safe with a low frequency of serious side-effects. Among the predictable and usually doserelated side-effects are bradycardia, bronchospasm, hypotension, muscle fatigue and cold extremities. Examples of unexpected side-effects are gastrointestinal symptoms such as nausea and disturbed intestinal motility, skin reactions, sexual dysfunction, as well as effects related to the central nervous system (CNS) such as emotional disturbances. The CNS-related side-effects, the mechanisms of which are unclear, consist of subtle effects on general well-being, decreased initiative, a depressed frame of mind and disturbed sleep. Generally, however, beta-blockers in therapeutic dosages do not affect the qualitative functions of the brain. Thus, all beta-blockers on the market seem to have high benefit-risk ratio, but independent of their physiochemical properties and pharmacodynamic profile, they seem to cause side-effects to about the same extent. The results so far available have been obtained by primarily using objective methods. Further comparison has now been initiated using documented subjective methods to investigate whether the objectively documented differences are of any clinical relevance to the patient's quality of life. Although it cannot be claimed with certainty, nonselective beta-blockers seem to cause CNS-related side-effects to a greater extent than beta 1-selective blockers. Differences in the degree of hydrophilicity of the beta-blocker are apparently of no clinical relevance in this respect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quality of life/subjective symptoms during beta-blocker treatment. 198 27

A double-blind controlled, randomized, parallel, multicenter 12-week study was conducted to compare the antihypertensive efficacy of lisinopril with that of metoprolol in treatment of moderate to severe hypertension. Initially, 118 patients were recruited on lisinopril and 61 on metoprolol; and for the purpose of efficacy analysis at week 8, 115 patients on lisinopril and 60 on metoprolol were included. The doses of lisinopril or metoprolol were 40-80 mg/day and 100-200 mg/day, respectively. At week 4, the pretreatment diastolic blood pressure of 111 mm Hg was decreased to 97 mm Hg (p less than 0.01) with lisinopril: metoprolol decreased the diastolic blood pressure from 110 to 99 mm Hg (p less than 0.01). Similar decreases were noted at week 8; however, the drop in blood pressure with lisinopril was not significantly different from that with metoprolol. Systolic blood pressure also demonstrated a decrease of about 18 mm Hg with lisinopril and 12 mm Hg with metoprolol (p less than 0.01). This larger decrease in systolic blood pressure with lisinopril was statistically significant at week 4 (p less than 0.05). These decreases in systolic blood pressures were maintained at week 8, again with statistical significance (p less than 0.01). Of the 118 lisinopril-treated patients, four were discontinued from lisinopril therapy because of headache, dizziness, rash, flushing, or lymphadenopathy. Four patients out of 61 (9.8%) were discontinued from metoprolol therapy because of fatigue, somnolence, asthenia, weight gain, flatulence, tremor, or bronchospasm. In conclusion, lisinopril 40-80 mg once daily is as effective as metoprolol 100-200 mg once daily in reducing diastolic blood pressure in patients with moderate to severe hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of antihypertensive efficacy of lisinopril compared to metoprolol in moderate to severe hypertension. 244 53

Hypophosphatemia has been recently highlighted as a reversible cause of respiratory muscle hypocontractility and reduced tissue oxygen extraction in patients with chronic obstructive lung disease and asthma. To define the prevalence and mechanism of hypophosphatemia under these circumstances, we studied phosphate homeostasis in 22 patients with chronic asthma, who had been hospitalized for emergency bronchodilator therapy. Serum phosphate concentration was normal in all patients on presentation, and fell after the initiation of bronchodilator therapy. Twelve patients (54%) developed hypophosphatemia (serum phosphate, less than 0.8 mmol/L). Urinary phosphate level fell in parallel. A negative correlation was observed between serum phosphate and serum theophylline concentrations, and a positive correlation between serum and urinary phosphate concentrations. No correlation was found between serum phosphate and serum albumin or urea concentration. These data indicate that hypophosphatemia is a common metabolic abnormality during the emergency treatment of asthma. The underlying mechanism appears to be drug-induced phosphate flux from the extra-cellular to the intracellular space. We suggest that the serum phosphate level be monitored in patients undergoing emergency treatment of bronchospasm, particularly if a prolonged period of bronchodilator therapy is required or if respiratory muscle fatigue supervenes.
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PMID:Hypophosphatemia complicating bronchodilator therapy for acute severe asthma. 280 3

During 10 years of clinical use involving almost 3 million patient-years, acebutolol has become established as a remarkably safe and well-tolerated beta-blocking agent, effective in treating essential hypertension and cardiac arrhythmias. The existence of a long-lived active metabolite (diacetolol) confers a 24-hour duration of action, which permits effective use of a once-daily regimen, particularly for hypertension. Acebutolol has low lipid solubility and low protein binding; the former property reduces the risk of central side effects, and the latter means that displacement interactions with other drugs are unlikely. Because acebutolol and its metabolite normally have both renal and hepatic excretion pathways, an alternative pathway is available should either be compromised through disease. Acebutolol is cardioselective, and clinical use has borne out the low incidence of bronchospasm in patients with impaired lung function. The possession of intrinsic sympathomimetic activity (ISA) leads to only modest reductions in cardiac output, which in turn reduces the chance of excessive bradycardia and the likelihood of precipitating heart failure. A combination of selectivity and ISA may be responsible for the low incidence of tiredness and cold extremities observed with acebutolol compared with other beta blockers. The unique pharmacologic and pharmacokinetic profile of acebutolol confers several therapeutic advantages and may be responsible for the generally low level of side effects experienced in clinical use.
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PMID:Acebutolol: ten years of experience. 285 85

beta-Blocking drugs are widely used throughout the world and serious adverse reactions are relatively uncommon. Most of those which do occur are pharmacologically predictable and may be avoided by ensuring that patients who are to be given beta-blockers do not have a predisposition to the development of bronchospasm, cardiac failure or peripheral ischaemia. In some situations, the use of a beta 1-selective blocking drug may reduce the risk of a severe adverse reaction, but there is little evidence that other ancillary properties such as partial agonist activity are of relevance in this context. Long term experience with many of the beta-blockers in current use suggests that unpredictable major adverse reactions such as the practolol oculomucocutaneous syndrome are unlikely to be repeated, although some of these drugs may be associated with immunological disturbances and some have been implicated in the development of retroperitoneal fibrosis. beta-Blocking drugs appear to be associated with a number of subjective side effects including muscle fatigue, peripheral coldness and some neurological symptoms. These side effects are highly subjective and are therefore difficult to quantify and it is not known whether they are of major importance in terms of their effect upon patients' overall well-being. It cannot be assumed that simply because such side effects can be elicited that they do, in fact, matter. However, because beta-blockers are often prescribed for patients who have no symptoms and for whom the benefits of therapy are generally small, such side effects would be of considerable importance if they had an overall effect upon quality of life. There are theoretical reasons to suppose that the incidence and severity of such side effects may be related to the ancillary properties of the individual drugs, but there is little evidence that parameters such as beta 1-selectivity, or partial agonist activity are clinically important determinants of the severity of these side effects. Lipophilicity, however, may be associated with an increased incidence of neurological symptoms. beta-Blocking drugs may cause a variety of metabolic disturbances including an increase in serum VLDL-cholesterol concentrations. However, long term studies have not shown that such disturbances are associated with an increased risk of cardiovascular disease, indicating that such metabolic changes may not be of major importance in practice. beta-Blocking drugs may be involved in a number of interactions with other drugs, but few of these have been shown to be of clinical significance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Adverse reactions and interactions with beta-adrenoceptor blocking drugs. 287 46

Adverse effects of beta-adrenergic receptor blocking drugs can be divided into two categories: 1) those that result from known pharmacological consequences of beta-adrenergic receptor blockade; and 2) other reactions that do not appear to result from beta-adrenergic receptor blockade. Adverse effects of the first type include bronchospasm, heart failure, prolonged hypoglycemia, bradycardia, heart block, intermittent claudication, and Raynaud's phenomenon. Neurological reactions include depression, fatigue, and nightmares. It is not yet proven whether the beta 1-selective adrenergic blockers or those with partial agonist activity reduce the overall frequency of adverse reactions seen with propranolol. Patient age does not appear, in itself, to be associated with more beta-blocker side effects. Side effects of the second category are rare. They include an unusual oculomucocutaneous reaction and the possibility of oncogenesis. There are also many drugs that interact with beta-blockers, which may increase toxicity. Finally, there are specific patient characteristics where one beta-blocker may be more effective and safer than another.
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PMID:Beta-adrenergic receptor blockers. Adverse effects and drug interactions. 289 72

Monitoring for adverse effects in an integral part of controlled clinical trials. Traditionally the results of monitoring are reported as either cumulative percentages at the end of the study or cross-sectional percentages at a given time in the study. These results are likely to underestimate the true number of complaints because participants may be withdrawn (e.g., deaths, losses to follow-up, and refusals) before they ever complain of an adverse effect. However, survival analysis methods can be used to compare the distributions of "time to first complaint" in the active and placebo treatment groups, taking into account withdrawals. Participants in the Beta-Blocker Heart Attack Trial were monitored for possible adverse effects. On each follow-up visit they were asked whether they had had any of four conditions (blacking out, fatigue, depression, and bronchospasm) since their previous visit about 3 months earlier. The patients were followed for up to 30 months. For fatigue and bronchospasm, the complaint-free time was significantly longer in the placebo vs. active (propranolol) treatment group (P less than 0.005).
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PMID:Survival analysis of adverse effects data in the Beta-Blocker Heart Attack Trial. 355 42


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