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)

The plasma prolactin response to a single-dose fenfluramine challenge is increasingly utilized in psychiatric research as an indirect and noninvasive measure of central serotonergic activity. However, the influences of age, gender, and body weight on prolactin response and characterization of physical and psychological symptoms evoked by fenfluramine remain poorly studied. In the current study, 83 nonpatient male and female volunteers, 25-60 years old, were administered a standardized fenfluramine challenge test (60 mg). Serial blood samples for plasma drug concentration and plasma prolactin concentration were obtained and side effects reported by participants were recorded. Analyses revealed that both plasma drug concentration and prolactin response were correlated with weight-relative dose (r = 0.43 and r = 0.38, respectively; p < 0.001). No significant relationship was noted between prolactin response and either age or gender. Symptoms during fenfluramine challenge were reported by 90% of subjects, most commonly fatigue, headache, lightheadedness, and difficulty concentrating. Overall side effect severity was related to weight-relative dose (r = 0.26; p < 0.05) and prolactin response (r = 0.42; p < 0.001). We conclude that fenfluramine challenge results should be reported as change in plasma prolactin relative to dose, and that in nonpatient samples the test is associated with frequent side effects.
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PMID:D,L-fenfluramine challenge test: experience in nonpatient sample. 873 16

Sleep apnea is associated with many adverse cardiovascular sequelae, including hypertension, nocturnal angina, decreased cardiac output, and bradyarrhythmias. The purpose of this study was to determine if patients referred for pacemaker therapy with asymptomatic bradyarrhythmias have underlying sleep apnea as the etiology of their bradyarrhythmias. This study included eight patients (7 males, 1 female) referred to a cardiac electrophysiology practice for pacemaker therapy. Patients included had asymptomatic bradyarrhythmias that consisted of severe sinus bradycardia, second-degree atrioventricular block, and complete heart block. In 7 of 8 patients, the bradyarrhythmias occurred at night or during the day while asleep. No patients were conditioned athletes. Symptoms often associated with bradyarrhythmias, such as lightheadedness and syncope, were not present. However, seven patients had at least one symptom suggestive of sleep apnea, such as excessive daytime fatigue, snoring, cessation of breathing during sleep (apnea), or frequent night-time awakenings. Overnight polysomnography studies were obtained on patients who had one or more symptoms suggestive of sleep apnea. In this study 7 of 8 patients (88%) referred for pacemaker therapy with asymptomatic bradyarrhythmias were documented by polysomnography to have sleep apnea. When treated with either sleep position modification, nasal continuous positive airway pressure (nasal CPAP), or tracheostomy, all seven patients had improvement in sleep apnea symptoms and remained asymptomatic from their bradyarrhythmias without pacemaker therapy over an average follow-up period of 22 months. One patient without symptoms suggestive of sleep apnea declined pacemaker therapy and remained asymptomatic. From these results, we concluded that asymptomatic transient bradyarrhythmias may suggest a diagnosis of sleep apnea. The evaluation of a patient referred for pacemaker therapy with asymptomatic bradyarrhythmias should include questions related to sleep apnea symptoms. Establishing the diagnosis of sleep apnea may reduce the need for pacemaker therapy and permit appropriate treatment of the underlying cause of these bradyarrhythmias.
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PMID:Asymptomatic bradyarrhythmias as a marker for sleep apnea: appropriate recognition and treatment may reduce the need for pacemaker therapy. 877 19

We studied the effect of 3 weeks treatment with the selective serotonin reuptake inhibitor (SSRI), fluvoxamine, on hormonal and psychological responses to buspirone, a 5-HT1A receptor partial agonist which also binds to dopamine receptors, in normal male volunteers. Eleven subjects received buspirone, 30 mg, and placebo before, and in week 3 of fluvoxamine treatment (mean dose 127 mg/day). Placebo and buspirone were given in a balanced order, double-blind. Buspirone significantly elevated plasma prolactin (PRL) and growth hormone (GH) concentrations but had no significant effect on cortisol (CORT) or temperature. Significant psychological effects of lightheadedness, tiredness and difficulty thinking occurred. Fluvoxamine treatment resulted in a nearly 3-fold increase in plasma buspirone with a similar enhancement of the PRL response. In contrast the GH and psychological responses were blunted. The increased buspirone concentrations are likely to be due to inhibition of first pass liver metabolism by fluvoxamine acting on the cytochrome P-450 system. The PRL response is probably mediated by antagonism of pituitary dopamine-D2 receptors and its enhancement by fluvoxamine treatment may be a pharmacokinetic effect. The blunting of GH and psychological responses suggest that 5-HT1A receptor function is reduced by chronic fluvoxamine treatment.
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PMID:The effect of chronic fluvoxamine on hormonal and psychological responses to buspirone in normal volunteers. 894 9

The safety and tolerability of mibefradil, a selective T-type calcium channel antagonist, were evaluated in 3,430 patients with essential hypertension and chronic stable angina pectoris treated in 15 double-blind placebo and active-controlled clinical trials and 2 open-label, long-term safety studies. Of these patients, 2,636 were treated with the recommended doses of mibefradil (50 and 100 mg) and form the basis of this report. With the 50-mg dose of mibefradil, the incidence of each adverse event was similar to, or lower than, that observed in the placebo-treated patients. Treatment with the 100-mg dose was associated with a slightly higher incidence compared to placebo of dizziness (2.1% vs 1.8%), leg edema (3.5% vs 1.4%), fatigue (2.1% vs 1.4%), and lightheadedness (2.1% vs 0.4%). The incidence of headache (4.6%) and angina pectoris (1.1%) was more frequent in patients treated with placebo. In active-controlled trials, a lower incidence of pedal edema (5.1%) was observed with mibefradil compared to amlodipine (25.7%), diltiazem SR/CD (9.4%), or nifedipine SR/GITS (17.4%). Overall, mibefradil was better tolerated than amlodipine and nifedipine SR/GITS and was as well tolerated as diltiazem SR/CD. Rates of premature discontinuation due to clinically adverse experiences with the 50- and 100-mg doses were 2.5% and 3.5%, respectively, compared with placebo (3.5%). No consistent pattern of laboratory adverse experiences were observed for mibefradil. Sinus bradycardia (heart rate <45 beats/minute) and first-degree atrioventricular block were the only relevant treatment-emergent electrocardiographic changes that occurred more frequently with mibefradil than with placebo. No evidence of first-dose effects was observed in mibefradil-treated patients, and withdrawal effects were not observed in clinical trials. There were no clinically important differences in safety profiles in the demographic subgroups for age, gender, or race. The results of this comprehensive safety analysis indicate that treatment with the recommended doses of mibefradil is well tolerated and safe.
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PMID:Safety of mibefradil, a new once-a-day, selective T-type calcium channel antagonist. 928 53

Head upright tilt table testing has emerged as an accepted modality for identifying an individual's predisposition to episodes of autonomically mediated hypotension and bradycardia that are sufficiently profound so that transient loss of consciousness ensues (neurocardiogenic syncope). However it has also become apparent that less dramatic falls in blood pressure, while not sufficient to cause full syncope, may produce symptoms such as near syncope, vertigo, dizziness, and TIA-like episodes. We have identified a subgroup of individuals with a mild form of autonomic dysfunction with symptoms of postural tachycardia and lightheadedness, disabling fatigue, exercise intolerance, dizziness, and near syncope. During baseline tilt table testing these patients demonstrated a heart rate increase of > or = 30 beats/min (or a maximum heart rate of 120 beats/min) within the first 10 minutes upright (unassociated with profound hypotension), which reproduced their symptom complex. In addition these patients exhibit an exaggerated response to isoproterenol infusions. Similar observations have been made by others who have dubbed this entity the Postural Orthostatic Tachycardia Syndrome (POTS). We conclude that POTS represents a mild (and potentially treatable) from of autonomic dysfunction that can be readily diagnosed during head upright tilt table testing.
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PMID:The postural orthostatic tachycardia syndrome: a neurocardiogenic variant identified during head-up tilt table testing. 930 45

Butyrates have been studied as cancer differentiation agents in vitro and as a treatment for hemoglobinopathies. Tributyrin, a triglyceride with butyrate molecules esterified at the 1, 2, and 3 positions, induces differentiation and/or growth inhibition of a number of cell lines in vitro. When given p.o. to rodents, tributyrin produces substantial plasma butyrate concentrations. We treated 13 patients with escalating doses of tributyrin from 50 to 400 mg/kg/day. Doses were administered p.o. after an overnight fast, once daily for 3 weeks, followed by a 1-week rest. Intrapatient dose escalation occurred after two courses without toxicity greater than grade 2. The time course of butyrate in plasma was assessed on days 1 and 15 and after any dose escalation. Grade 3 toxicities consisted of nausea, vomiting, and myalgia. Grades 1 and 2 toxicities included diarrhea, headache, abdominal cramping, nausea, anemia, constipation, azotemia, lightheadedness, fatigue, rash, alopecia, odor, dysphoria, and clumsiness. There was no consistent increase in hemoglobin F with tributyrin treatment. Peak plasma butyrate concentrations occurred between 0.25 and 3 h after dose, increased with dose, and ranged from 0 to 0.45 mM. Peak concentrations did not increase in three patients who had dose escalation. Butyrate pharmacokinetics were not different on days 1 and 15. Because peak plasma concentrations near those effective in vitro (0.5-1 mM) were achieved, but butyrate disappeared from plasma by 5 h after dose, we are now pursuing dose escalation with dosing three times daily, beginning at a dose of 450 mg/kg/day.
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PMID:Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors. 953 30

Past studies have shown that severe fatigue was the presenting symptom in six of seven patients with delayed orthostatic hypotension and that tilt table-induced hypotension was found in 22 of 23 patients with the chronic fatigue syndrome. We have determined the prevalence of fatigue, volunteered in response to a nonspecific pre-examination questionnaire used in 431 patients, each subsequently diagnosed as having one of eight neurological or endocrine disorders. The results show that fatigue is a very common symptom in patients with delayed orthostatic hypotension (n = 21), as well as both primary (n = 30) and secondary (n = 106) hypocortisolism: 70-83% in all groups. In contrast, fatigue was an uncommon complaint in patients with multiple system atrophy (MSA) (n = 30), pituitary disorders without hypocortisolism (n = 106) or idiopathic hirsutism (n = 96): 7-33% in all groups, and was intermediate in prevalence in patients with acute hyperadrenergic orthostatic hypotension (n = 32): 41%. It is concluded that fatigue commonly results from delayed orthostatic hypotension and all forms of hypocortisolism but is less common in patients with acute orthostatic hypotension, both idiopathic and due to MSA, which more commonly present with lightheadedness or syncope.
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PMID:The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue. 961 2

Preclinical studies indicate that dihydropyridine-type calcium channel antagonists modulate dopamine neurotransmitter function and can reduce cocaine-reinforced behaviors. Amlodipine, a long-acting dihydropyridine-type calcium channel antagonist related to isradipine and nifedipine, was administered in open label fashion for 12 weeks to 26 cocaine-dependent patients. In subjects expressing cocaine craving, craving significantly declined during the course of the 12 weeks. Five individuals reported flushing, headache, fatigue, nocturia, nausea, and lightheadedness. No conclusions regarding efficacy can be made due to the small number of subjects and the open-label design.
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PMID:Amlodipine treatment of cocaine dependence. 1043 93

Head upright tilt table testing has become an accepted method to measure an individual's predisposition to autonomically mediated periods of hypotension and bradycardia severe enough to cause frank syncope. At the same time it has become increasingly apparent that less profound falls in blood pressure, while not sufficient to result in loss of consciousness, may cause symptoms such as near syncope, vertigo, and dizziness. We describe a subgroup of adolescents that have a mild form of autonomic dysfunction that exhibit disabling symptoms such as postural tachycardia and palpitations, extreme fatigue, lightheadedness, exercise intolerance, and cognitive impairment. During baseline tilt table testing at a 70 degrees angle, these patients demonstrated a heart rate increase of > or = 30 beats/min (or a maximum heart rate of > or = 120 beats/min) within the first 10 minutes upright (not associated with profound hypotension), which reproduced their clinical symptom complex. Similar observations have been made in the adult population and has been termed the postural orthostatic tachycardia syndrome (POTS). We report that POTS may also occur in adolescents and represents a mild, potentially treatable form of autonomic dysfunction that can be readily identified during head upright tilt table testing.
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PMID:The postural orthostatic tachycardia syndrome: a potentially treatable cause of chronic fatigue, exercise intolerance, and cognitive impairment in adolescents. 1075 Jan 35

Stimulated by the widespread use of head-up tilt testing, transient episodes of neurocardiogenically mediated hypotension and bradycardia have become a well recognized cause of recurrent syncope and near syncope (generally referred to as neurally mediated syncope). On the other hand, a large subgroup of patients was identified, who appeared to have a less severe hypotension and orthostatic intolerance that is characterized by postural tachycardia, exercise intolerance, disabling fatigue, lightheadedness and dizziness. This form of disability has been recognized as postural orthostatic tachycardia syndrome (POTS). While the etiology of POTS is still unclear, a mild form of idiopathic peripheral autonomic neuropathy (partial dysautonomia) or beta-receptor hypersensitivity has been suggested for the pathophysiology of this disorder. A detailed history and physical examination that includes a careful neurologic examination are essential for diagnosis. Head-up tilt testing is often useful as a standardized measure of response to postural change. This review summarizes the history, current knowledge of clinical features, diagnosis and therapeutic strategies.
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PMID:[Idiopathic postural orthostatic tachycardia syndrome] 1101 90


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