Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Rizatriptan and sumatriptan are selective 5-HT(1B/1D) receptor agonists for theacute treatment of migraine. For oral formulations, the time to maximum plasma concentration is reached earlier with rizatriptan than with sumatriptan (1 h versus 2-2.5 h) and rizatriptan has greater bioavailability than sumatriptan (45% versus 15%). These pharmacological advantages appear to translate into a faster onset of action and a better overall response for oral rizatriptan versus oral sumatriptan. The two drugs have been directly compared in randomized, double-blind, placebo-controlled clinical trials of patients with moderate or severe migraine attacks. Rizatriptan 10 mg was generally superior to sumatriptan on a measure of time-to-pain-relief within 2 h, where pain relief was defined as a reduction of pain to mild or none (odds ratio for rizatriptan versus sumatriptan 100 mg = 1.21; odds ratios for rizatriptan 10 mg versus sumatriptan 50 mg = 1.14 and 1.10 in two studies). Rizatriptan 10 mg was also superior to sumatriptan on the International Headache Society recommended endpoint of the percentage of patients pain free at 2 h (40% for rizatriptan 10 mg, 33% for sumatriptan 100 mg, and 35% for sumatriptan 50 mg). Further advantages for rizatriptan were seen on stringent outcome measures of the percentage of patients who were completely free of all symptoms at 2 h, patient satisfaction with medication at 2 h, and 24-h sustained pain-free response. 5-HT(1B/1D) receptor agonists are contraindicated in patients with coronary artery disease because of their potential to cause vasoconstriction. In clinical trials which excluded such patients, rizatriptan and sumatriptan were both well-tolerated. The most common side-effects on both drugs occurred in <10% of patients and consisted of dizziness, drowsiness, and asthenia/fatigue. The adverse events were usually mild or moderate in severity and short-lasting.
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PMID:Rizatriptan: pharmacological differences from sumatriptan and clinical results. 1246 79

Frovatriptan is a 5-HT(1B/1D) agonist demonstrating consistently effective headache relief at a low dose of 2.5 mg. A striking pharmacokinetic characteristic is its long half-life of 25 h. This is balanced by an average Tmax of 2-3 h, a low degree of lipophilicity and a low oral bioavailability of 24-30%. Fifty per cent of the drug is renally excreted and the rest is partially metabolized by P450 CYP 1A2. In three short-term multicentre, double-blind, placebo-controlled phase III trials, the 2 h headache response for 2.5 mg frovatriptan varied from 36 to 46% (placebo 21-27%). The 4 h headache responses were considerably higher--up to 65%. Thirty-five per cent of patients were consistent rapid responders. The recurrence rate was 10-25%. In addition to effective and prolonged relief of head pain, frovatriptan reduced associated migraine symptoms such as nausea, photophobia and phonophobia. There was an excellent tolerability profile with the incidence of adverse events for frovatriptan only slightly higher than placebo. The most commonly reported adverse events for both frovatriptan and placebo were dizziness, nausea, headache and fatigue.
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PMID:Frovatriptan: pharmacological differences and clinical results. 1246 82

Depression is increasingly being recognized as a common comorbid disorder in patients with severe and chronic medical conditions. However, patients with depression and anxiety frequently present with somatic complaints such as aches and pains, headache, and chronic fatigue. This leads to underrecognition and undertreatment of the psychiatric disorder in an attempt to identify the medical cause of the somatic complaint. Reports are demonstrating the efficacy of antidepressants in treating disorders other than depression and anxiety. Tricyclic antidepressants have shown their usefulness in the treatment of diabetic neuropathy, fibromyalgia, and headache. Controlled studies of several selective serotonin reuptake inhibitors have been shown to be efficacious in relieving the symptoms of premenstrual dysphoric disorder and fibromyalgia. Pilot studies have also been conducted with the serotonin and norepinephrine reuptake inhibitor venlafaxine for the treatment of diabetic neuropathy, fibromyalgia, migraine, premenstrual dysphoric disorder, and stroke. The results encourage further controlled studies.
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PMID:Coping with somatic comorbidities: striving for complete recovery. 1249 Aug 26

Noxious stimuli and painful disorders interfere with sleep, but disturbances in sleep also contribute to the experience of pain.Chronic paroxysmal hemicrania and possibly cluster headaches are related to REM sleep. Whereas headache is associated with snoring and sleep apnea, morning headaches are not specific for any primary sleep disorder. Nevertheless, the management of the sleep disorder ameliorates both morning headache and migraine.Noxious stimuli administered into muscles during slow-wave sleep (SWS) result in decreases in delta and sigma but an increase in alpha and beta EEG frequencies during sleep. Noise stimuli that disrupt SWS result in unrefreshing sleep, diffuse musculoskeletal pain, tenderness, and fatigue in normal healthy subjects. Such symptoms accompany alpha EEG sleep patterns that often occur in patients with fibromyalgia. The alpha EEG patterns include phasic and tonic alpha EEG sleep as well as periodic K alpha EEG sleep or frequent periodic cyclical alternating pattern. Moreover, alpha EEG sleep, as well as sleep-related breathing disorder and periodic limb movement disorder, occur in some patients with fibromyalgia, rheumatoid arthritis and osteoarthritis. Depression and not alpha EEG sleep are features of somatoform pain disorder. Disturbances in sleep, pain behaviour and psychological distress influence return to work in workers who have suffered a soft tissue injury, e.g. low back pain. Patients with irritable bowel disorder have disturbed sleep and have increased REM sleep. In conclusion, there is a reciprocal relationship between sleep quality and pain. The recognition of disturbed or unrefreshing sleep influences the management of painful medical disorders.
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PMID:Sleep and pain. 1253 Oct 4

This study investigated the intensity of stress, anxiety and depression in a sample of 141 migraineurs compared with a control group of 109 non-migraine workers matched for age and sex. Stress was measured using the Perceived Stress Questionnaire, and anxiety and depression using the Hospital Anxiety and Depression Scale. Results indicated that stress and anxiety were higher in the migraine group than in the control group and above the clinical level. Depression scores remained low in both groups, under clinical relevance. Stress is a primordial factor in the triggering and perpetuation of migraine attacks. The high score of the items 'morning fatigue', 'intrusive thoughts about work', 'feeling under pressure', 'impatience', and 'irritability' of the stress questionnaire in the migraineurs is particularly significant in the intensive stress response. It seems necessary to manage stress to improve the daily life of migraineurs and to study the link between stress, anxiety and migraine.
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PMID:Stress, anxiety, depression and migraine. 1280 24

Migraine is a chronic headache disorder manifesting in attacks lasting 4-72 hours. Characteristics of headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity, and association with nausea, photophobia and phonophobia. The migraine aura is a complex of neurological symptoms, which occurs just before or at the onset of migraine headache. Botulinum toxin A represents a completely new option for patients with chronic pain conditions. Numerous retrospective open-label chart reviews and 4 double-blind, placebo-controlled studies have demonstrated that botulinum toxin type A is significantly effective in migraine prophylaxis and reduces the frequency, severity, and disability associated with migraine headaches. Studies have generally reported a good and consistent efficacy. The differential therapeutic use of botulinum toxin appears to be worth attempting in migraine patients with the following characteristic features: (1) Muscular stress as migraine trigger, e. g., in craniocervical dystonia, pericranial painful muscular trigger points or tender points, oromandibular dysfunction, (2) concurrent chronic tension-type headache with the aggravating factors of muscular stress or oromandibular dysfunction, (3) chronic migraine with frequent migraine attacks on more than 15 days per month for longer than 3 months and if other therapeutic options have been either ineffective or have not been tolerated. The use of the agent does not cause CNS side effects. Migraine patients in particular, often suffer greatly, as a result of the adverse effects of the drugs used, from fatigue, dizziness, reduced concentration, loss of appetite, weight gain, hair loss and changes in libido. These side effects are not known in association with botulinum toxin A. To date, neither organic damage nor allergic complications have been reported. Thus, both the tolerability and the safety of this therapeutic measure are high. The mode of action by which botulinum toxin is effective in migraine prophylaxis is not fully understood and is under investigation. Currently, a number of other randomized, placebo-controlled, clinical trials are being conducted to evaluate the efficacy, optimal dosing, and side-effect profile of botulinum toxin type A in the prophylaxis of migraine and other headache entities.
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PMID:Botulinum toxin in migraine prophylaxis. 1499 36

Migraine is one of the leading causes of disability. Topiramate has multiple mechanisms and may reduce neurotransmission through the trigeminocervical complex to prevent migraine. In clinical trials for the prevention of migraine, the mean monthly migraine frequency decreased from 5.6 to 4.5 in the placebo group and larger decreases were observed with topiramate (100 mg/day, 5.8 to 3.5; 200 mg/day, 5.1 to 3.0). However, topiramate use is associated with a high incidence of adverse events (paraesthesia, fatigue, anorexia, diarrhoea), which may limit the willingness of patients to use topiramate for the prevention of migraine. BIBN 4096 BS is a non-peptide calcitonin gene-related peptide-receptor antagonist that has recently been trialled in migraine attacks. The primary efficacy end point was the reduction of severe or moderate headache prior to treatment to mild or no headache at 2 h. This endpoint was achieved in 21 of 32 (66%) patients with BIBN 4096 BS 2.5 mg, compared to 27% of patients given placebo. Although BIBN 4096 BS is a non-peptide, it is still administered intravenously, which will probably limit its use to medical centres.
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PMID:New drugs for the prevention and treatment of migraine: topiramate and BIBN 4096 BS. 1501 83

BIBN 4096 BS ([R-(R*,S*)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-piperidinecarboxamide) is the first selective, highly potent, small molecule, nonpeptide calcitonin gene-related peptide (CGRP) receptor antagonist, which has been developed for the treatment of acute migraine. The objective of this study was to obtain information on the safety, tolerability and pharmacokinetics of BIBN 4096 BS following single intravenous administration of rising doses (0.1, 0.25, 0.5, 1, 2.5, 5 and 10 mg) in 55 healthy male and female volunteers. The study was of single-centre, double-blind (within dose levels), placebo-controlled, randomized, single rising dose design. Blood pressure, pulse rate, respiratory rate, ECG, laboratory tests and forearm blood flow did not reveal any clinically relevant, drug-induced changes. Sixteen adverse events (AEs) were reported by eight of 41 volunteers after BIBN 4096 BS compared to five AEs reported by four of 14 volunteers after placebo. Approximately two-thirds of all AEs related to active treatment occurred at the highest dose of 10 mg. At this dose level, all AEs were confined to the three BIBN 4096 BS-treated females, and consisted mainly of transient and mild paresthesias. Paresthesias were the single most frequent AE, whereas fatigue was the AE which occurred in the highest number of subjects. Only two AEs were of moderate intensity, all remaining AEs were of mild intensity. No serious AEs were reported. The local tolerability after intravenous administration was good. In summary, intravenously administered BIBN 4096 BS revealed a very favourable safety profile over the dose range tested in both genders. Generally well tolerated at all dose levels, it was of satisfactory tolerability in female subjects at the highest dose of 10 mg. The plasma concentration-time courses of BIBN 4096 BS showed multicompartmental disposition characteristics. Mean maximum concentration (Cmax) values appeared to be dose-proportional. Based on the results from the two high dose levels (5 and 10 mg) with sufficient individual subject data, BIBN 4096 BS exhibited a total plasma clearance (CL) of approximately 12 l/h and an apparent volume of distribution at steady state (Vss) of approximately 20 l, resulting in a terminal half-life (t1/2) of approximately 2.5 h. Inter-individual variability was moderate with a coefficient of variation of approximately 45% based on the area under the plasma concentration-time curve (AUC) values. The mean renal clearance (CLR) was approximately 2 l/h, suggesting that renal excretion plays only a minor role in the elimination of unchanged BIBN 4096 BS.
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PMID:Safety, tolerability and pharmacokinetics of BIBN 4096 BS, the first selective small molecule calcitonin gene-related peptide receptor antagonist, following single intravenous administration in healthy volunteers. 1526 53

Frovatriptan succinate is one of the most recent serotonin receptor agonists to receive FDA, approved labelling for use in the acute management of migraine with or without aura in adults. The mechanism of action of frovatriptan is thought to be similar to that of a serotonin agonist. However, frovatriptan has distinctive pharmacokinetic and pharmacologic properties, chiefly, a high affinity for serotonin receptors 1B and 1D and a long elimination half-life; frovatriptan was shown to be more selective for cerebral than coronary arteries, a property which makes frovatriptan more favourable in patients at risk of coronary artery disease. Additionally, frovatriptan has a half-life of approximately 25 h, substantially longer than that of any other agent within its class. This property makes frovatriptan suitable for patients who typically suffer migraines of long duration and/or those who suffer migraine recurrence. The efficacy of frovatriptan in the treatment of acute migraine was demonstrated in five double-blind, randomised, placebo-controlled trials. At 2h, headache response rates for frovatriptan 2.5 mg ranged from 38 to 40% compared to 22-35% for placebo. Headache recurrence for frovatriptan 2.5 mg at 24h ranged from 9 to 14% compared with 18% in placebo subjects. Frovatriptan has no clinically significant pharmacokinetic interactions with drugs used for migraine prophylaxis or with commonly prescribed medications. Adverse effects of frovatriptan including dizziness, paresthesia, dry mouth, fatigue and flushing were generally mild and well tolerated. Given the fact that patient response to serotonin agonists is individualised, and selecting an effective agent may involve trial and error, frovatriptan is a welcome alternative in the acute management of migraine.
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PMID:Frovatriptan succinate, a 5-HT1B/1D receptor agonist for migraine. 1531 27

Several studies have shown that atmospheric conditions can affect well-being or disease, and that some individuals seem to be more sensitive to weather than others. Since epidemiological data on the prevalence of weather-related health effects are lacking, two representative weather sensitivity (WS) surveys were conducted independently in Germany and Canada. The objectives of this paper are: (1) to identify the prevalence of WS in Germany and Canada, (2) to describe weather-related symptoms and the corresponding weather conditions, and (3) to compare the findings in the two countries. In Germany 1,064 citizens (age >16 years) were interviewed in January 2001, and in Canada 1,506 persons (age >18 years) were interviewed in January 1994. The results showed that 19.2% of the German population thought that weather affected their health "to a strong degree," 35.3% that weather had "some influence on their health" (sum of both = 54.5% weather sensitive), whereas the remaining 45.5% did not consider that weather had an effect on their health status. In Canada 61% of the respondents considered themselves to be sensitive to the weather. The highest prevalence of WS (high + some influence) in Germans was found in the age group older than 60 years (68%), which was almost identical in the Canadian population (69%). The highest frequencies of weather-related symptoms were reported in Germany for stormy weather (30%) and when it became colder (29%). In Canada mainly cold weather (46%), dampness (21%) and rain (20%) were considered to affect health more than other weather types. The most frequent symptoms reported in Germany were headache/migraine (61%), lethargy (47%), sleep disturbances (46%), fatigue (42%), joint pain (40%), irritation (31%), depression (27%), vertigo (26%), concentration problems (26%) and scar pain (23%). Canadian weather-sensitive persons reported colds (29%), psychological effects (28%) and painful joints, muscles or arthritis (10%). In Germany 32% of the weather-sensitive subjects reported themselves to be unable to do their regular work because of weather-related symptoms at least once in the previous year, and 22% of them several times. Co-morbidity was significantly higher in weather-sensitive subjects both in Germany and Canada. These results clearly showed the important impact of WS on public health and the economy. These findings prompted us to start studies on the causal factors of weather-related health effects.
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PMID:Prevalence of weather sensitivity in Germany and Canada. 1533 86


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