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)

Amlodipine, a potent long-acting dihydropyridine calcium antagonist, was compared with placebo in a parallel, randomized, double-blind study in 134 patients with chronic stable angina pectoris maintained on beta-adrenergic blocking agents. After a single-blind, two-week placebo period, patients were randomized to receive either amlodipine (2.5, 5, and 10 mg) or placebo once daily for four weeks. The effects of amlodipine on maximal exercise time, work, time to angina onset, and subjective indices including angina frequency, nitroglycerin tablet consumption, and patient and investigator ratings were assessed. Each dose of amlodipine produced increases in exercise time and calculated total work accomplished compared to baseline. Improvements at 5 and 10 mg were significantly greater than placebo which produced no significant change (p less than 0.05). Qualitative improvements in the severity of angina were produced by amlodipine at 5 and 10 mg daily assessed by patient-rating questionnaires (p less than 0.05). Reductions in angina frequency attacks per week and weekly nitroglycerin tablet consumption occurred but were not statistically significant when compared with placebo. Adverse effects observed during amlodipine treatment prompted discontinuation of treatment in only 2 out of 100 patients. Three patients discontinued treatment for reported lack of efficacy. No laboratory abnormalities prompted treatment discontinuation and minor side effects of dizziness, nausea, headache, and fatigue were observed infrequently. The results of this controlled, large-scale multicenter trial suggest that amlodipine significantly increased exercise capacity and was well tolerated when added to the antianginal regimen of patients remaining symptomatic while receiving beta-blocking agents.
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PMID:Amlodipine combined with beta blockade for chronic angina: results of a multicenter, placebo-controlled, randomized double-blind study. 135 85

The effects of epanolol (a new selective beta-adrenoceptor antagonist), diltiazem and placebo were compared in a group of 16 patients with chronic stable angina pectoris. Each patient received each treatment in random order. Diltiazem reduced weekly angina attack rate from 7.2 (95% CI 3.9-10.5) to 3.9 (1.9-5.9) (P less than 0.01), whereas a lesser reduction was observed after epanolol. Both drugs produced a small but significant (P less than 0.05) increase in treadmill exercise time (placebo 474 s (374-574), epanolol 527 s (431-623) and diltiazem 554 s (462-646). However, aerobic work capacity, assessed by peak achieved oxygen consumption, was not different from the placebo value of 21.2 (18.0-24.4) ml.min-1.kg-1, and clearly subnormal when compared to age- and sex-matched controls (33.0 (30.1-35.9) ml.min-1.kg-1). Ventilatory abnormalities and increased lactate levels on active treatment were observed at peak exercise only. We conclude that the cardiodepressant effects of both active drugs limit blood supply to working skeletal muscle, and that chest pain may be replaced by dyspnoea or fatigue as the limiting factors to exercise.
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PMID:Comparative effects of epanolol and diltiazem on exercise performance and respiratory gas exchange in angina pectoris. 135 16

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

The adequate treatment of a disease syndrome is dependent upon a clear definition of the symptomatic, pathological, physiological and prognostic targets against which therapy is to be deployed. The syndromes of ischaemic heart disease, including angina pectoris, are complex in origin, pathology, pathophysiology and natural history, and a complete clinical profile is difficult, if not impossible, to achieve in individual patients. The prime goals of pharmacotherapy in ischaemic heart disease are easy to define, but difficult to accomplish in practice. Relief of pain, breathlessness and fatigue are the prime clinical targets for pharmacotherapy. In view of their sinister significance, the electrophysiological indications of myocardial ischaemia, whether symptomatic or silent, are also crucial targets towards which therapy must be directed. Ischaemic heart disease is accompanied by a wide variety of regional and global abnormalities of myocardial contractile function associated with widespread reflex stimulation of the peripheral vascular system and neuroendocrine systems. Primarily, drug therapy must be directed at correction of these pathophysiological components of the syndrome. Longer term but no less essential goals in the treatment of ischaemic heart disease are the prevention of the clinical sequelae of the syndrome and its progression. A natural sequel of coronary artery obstructive disease is successive thrombotic events and loss of myocardium. Calcium antagonists, by preventing the increase in myocardial cytosolic calcium during acute ischaemic episodes, defer cell necrosis; in this respect, they are unique among currently available antianginal drugs. With regard to progression, the prime pathological cause of ischaemic heart disease is coronary atheroma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapeutic targets in ischaemic heart disease. 137 82

Symptoms of depression in the majority of patients immediately following acute myocardial infarctions (AMI) resolve rapidly; they are an adjustment reaction. However, in a group of 552 male patients there were 80 (14.5%) patients with persistent major depressive symptoms during a finite period after AMI. Infarction size was assessed by maximum creatine kinase levels, the QRS-complex and the occurrence of late potentials. These measures did not correlate with the degree of depressed moods in these groups. An arrhythmic event in the early hospitalization phase, a recurrent infarction, dyspnoea, and persistent angina pectoris before the AMI were significantly related to more profound degrees of depression. Patients who reported serious life-events in the last 2 yr before AMI, or who suffered from exhaustion and fatigue in the prehospital phase were subject to significantly higher levels of depression. A prodromal phase prior to hospitalization free of bodily symptoms and the use of denial were related to low levels of depression. The logistic regression model incorporating all univariate significant variables revealed that symptoms of exhaustion and fatigue prior to AMI had the strongest independent correlation with post AMI depression.
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PMID:Factors which provoke post-infarction depression: results from the post-infarction late potential study (PILP). 143 62

Iron deficiency, the most common cause of anemia, is prevalent in 10 percent to 30 percent of the world's population. Inadequate intake of iron may be an important causative factor, particularly when the body requires more iron than usual (e.g., during infancy, early childhood, adolescence, pregnancy and periods of blood loss). The popular increase of fiber in diets may increase the incidence of iron-deficiency anemia because too much fiber in the diet renders available iron unabsorbable. Symptoms in children include skin or conjunctival pallor, excessive sleepiness, learning disabilities, diminished attention span, tiredness, irritability or inappropriate behavior, and pica. Adults may have shortness of breath, decrease in exercise tolerance, palpitations, tachycardia, angina, congestive heart failure, orthopnea and edema. Iron deficiency occurs in sequential states and is measured by many laboratory tests. The levels of hemoglobin and hematocrit are both decreased, while the red blood cell count may be normal initially, but will decrease as the iron-deficiency state continues. The steps of treatment include correction of the underlying disorder, administration of the amount of iron needed and observation of the response to treatment.
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PMID:A guide to primary care of iron-deficiency anemia. 143 77

The calcium antagonist, diltiazem is effective in the treatment of patients with various types of angina pectoris, as well as with essential and renovascular arterial hypertension. Sustained-release diltiazem in dose of 180 mg once daily is effective as sustained-release diltiazem in dose of 90 mg twice daily. Besides, in patients with stable angina pectoris and essential arterial hypertension the monotherapy with sustained-release diltiazem in dose of 180 mg is similarly effective as beta blockers and thiazide diuretics. However, monotherapy with sustained-release diltiazem is at least effective as monotherapy with sustained-release verapamil. Comparative clinical investigations showed that diltiazem is more effective than propranolol in decreasing ischemic attacks, whereas the risk of bradycardia is smaller. On the other hand, nifedipine (dihydropyridine calcium antagonist) is more effective than diltiazem in lowering ischemic electrocardiographic changes, incidence of attacks and improving working capability. The efficacy of diltiazem, nifedipine and verapamil is similar in the treatment of patients with spastic angina pectoris, whereas the least effective is propranolol. As far as the arterial hypertension is concerned, clinical investigations showed that the efficacy of diltiazem and nifedipine is similar. Side effects are relatively rare (1.8-9.6% patients) and depend on the dose (nausea, fatigue, dizziness, headache and itching).
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PMID:[Pharmacology--new therapy. Calcium channel blockers: new aspects of therapeutic use of diltiazem]. 146 75

Clentiazem, 8-chloro diltiazem, is a calcium channel blocker currently undergoing evaluation for the treatment of stable angina and hypertension. As patients with ischaemic disorders often present some degree of heart failure, the aim of this study was to investigate the effect of congestive heart failure on clentiazem (200 micrograms kg-1, i.v. bolus) pharmacokinetics in a canine model. Congestive heart failure was induced in six dogs by rapid ventricular pacing (240 beats min-1) for 3-5 weeks. Clentiazem pharmacokinetics was studied in each dog under the control condition and after the development of clinical signs of heart failure (ascites, dyspnea, fatigue). Blood samples were collected up to 480 min post-dose. Clentiazem plasma concentrations were determined by high performance liquid chromatography. The area under the plasma concentration versus time curves (AUC0-infinity) was significantly increased in congestive heart failure dogs (8.8 +/- 1.6 vs 21.8 +/- 1.4 micrograms min ml-1) (mean +/- SEM). These changes were related to a reduction of the volume of distribution of the central compartment (0.9 +/- 0.1 vs 0.2 +/- 0.11 kg-1) and total body clearance (1.9 +/- 0.4 vs 0.7 +/- 0.21 h-1 kg-1). It is concluded that, in our model, congestive heart failure significantly modifies clentiazem disposition. These results suggest that caution should be exercised when clentiazem is given to patients with a low ejection fraction and a compromised cardiac function. Reduced loading and maintenance doses might be recommended in patients with severe congestive heart failure.
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PMID:Effect of congestive heart failure on clentiazem pharmacokinetics in a dog model. 148 42

Silent myocardial ischaemia is now well-recognised in patients with symptomatic coronary artery disease. Its pathogenesis remains speculative, though diminished sensitivity to pain is thought to be one of the mechanisms involved. Because cardiovascular autonomic dysfunction occurs frequently in diabetic patients, we postulate that it contributes towards painless myocardial ischaemia among them. Forty consecutive diabetic (type II) male patients and ten normal volunteers were studied. Using 5 previously-validated noninvasive tests for autonomic dysfunction, 14 of these diabetic men had definite autonomic neuropathy (at least 2 abnormal tests). All 50 subjects were then exercised on a motor-driven treadmill to either exhaustion or chest pains. Thirty-three diabetic subjects were tested positive, with significant (greater than 1 mm) ST segment depression over at least 2 contiguous leads. Of these, 18 were associated with typical angina but the other 15 stopped because of fatigue or exhaustion (ie painless). Thirteen subjects who had definite autonomic neuropathy (AN+) had positive exercise ECG tests-10 had painless ischaemia, and only 3 had angina. This contrasted with 15 patients who had painful ischaemia and 5 who had painless ischaemia among the group without (AN-)autonomic dysfunction (p = 0.0047, Fisher's exact test). There were no significant differences among the various groups for peak rate-pressure-product, all subjects attaining similar maximal oxygen consumption states during which ischaemic ST segment changes were noted (painful AN+: 21917 +/- 4753; painless AN+: 20117 +/- 6752; painful AN-: 16544 +/- 4063; painless AN-: 22220 +/- 4341, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association of diabetic autonomic neuropathy with painless myocardial ischaemia induced by exercise. 162 Nov 24

The timing of valve replacement in patients with mitral valve disease, severe resting pulmonary hypertension, and severe symptoms is usually straightforward. However, this may not be true for patients with mild to moderate resting pulmonary pressures and symptoms that are difficult to evaluate. The measurement of hemodynamic parameters with exercise has been useful during cardiac catheterization. The purpose of this study was to evaluate the hemodynamic significance of dyspnea provoked by exercise in patients with mitral valve disease using exercise Doppler echocardiography. Nineteen tests were done in 17 patients (two patients had repeat studies 1 year after the first test). Dyspnea developed in patients during exercise in 11 tests, and the others were limited by fatigue (and angina in one patient). There was a significantly greater increment in pulmonary artery systolic pressure during exercise in the patients who developed dyspnea (24 mm Hg) than in those who did not (15 mm Hg, p = 0.04). The two groups exercised to approximately the same heart rate and blood pressure, but the dyspneic patients had a significantly shorter exercise capacity (p = 0.04). Furthermore, clinical decision making was affected by the test results in 84% (only three tests did not affect patient management) and included a decision to proceed to invasive testing and surgery in seven patients, and a decision to treat the patient medically in nine. In conclusion, exercise Doppler echocardiography is a useful adjunct in the diagnosis and treatment of patients with mitral valve disease and an aid to clinical decision making.
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PMID:Exercise Doppler echocardiography as an aid to clinical decision making in mitral valve disease. 162 12


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