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

Chronic low blood pressure is typically accompanied by symptoms such as fatigue, reduced drive, dizziness, headaches and cold limbs. Reduced cognitive performance, diminished cerebral blood flow and autonomic dysregulation have been furthermore documented in this condition. The present contribution reports two studies exploring systemic hemodynamics in chronic hypotension and their modification through vasopressor application. In study I, effects of the alpha-sympathomimetic midodrine were examined in 54 hypotensive individuals using a placebo-controlled double-blind design. Hemodynamic parameters were assessed at rest and during mental stress. They were derived from continuous blood pressure recordings using Modelflow analysis. The drug led to marked increases in blood pressure, total peripheral resistance and stroke volume. However, due to strong heart rate deceleration, cardiac output remained virtually unchanged. In study II, 40 hypotensive and 40 normotensive control persons were compared with respect to hemodynamics. While groups did not differ in total peripheral resistance, hypotensives exhibited markedly diminished stroke volume and heart rate, resulting in a reduction in cardiac output of 25% at rest and of 33% during mental stress. The data provide relevant knowledge about the hemodynamic mediation of chronic hypotension. In contrast to elevated blood pressure, which is mainly determined by increased peripheral resistance, reduced cardiac output may be the cardinal hemodynamic aberration in chronic hypotension. Midodrine proved to be effective in elevating blood pressure. However, given the cardiac origin of chronic hypotension and the lack of drug effect on cardiac output, alpha-sympathomimetic treatment may be suboptimal.
 ...
PMID:Hemodynamic determinants of chronic hypotension and their modification through vasopressor application. 1934 May 50

Anaerobic endurance training (AET) can improve sympathomimetic hyperactivity, and anaerobic interval training (AIT) is recommended for patients who cannot exercise due to exertional breathlessness and leg fatigue. However, the difference in sympathetic nerve activation (SNA) and parasympathetic nerve activation (PNA) during AIT and AET is unclear. The aim of this study is to investigate the differences between endurance and interval trainings. We studied three patients (63-73 years) assigned to AIT which exercise/pause phase is 60/120 seconds (AIT120) and AET of 10 minutes duration. Systolic blood pressure, heart rate (HR), and rate pressure product (as an index of SNA) and oxygen uptake, tidal volume, respiratory rate, and minute ventilation were measured. As a result, these parameters in AET were increased compared with those of AIT120 among the subjects. While, high frequency component of frequency distribution in HR (HF) in AET was decrease compared with that in AIT120 among subject. We concluded that AIT inhibited SNA more effectively compared with AET and AIT may be safe for cardiac rehabilitation.
 ...
PMID:Effectiveness of interval training compared with endurance training in cardiac rehabilitation. 2225 85

Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system, leading to chronic disability. Fatigue is a common and distressing symptom of MS which is unrelated to its clinical form, stage of development, the degree of disability, or the lesion load on magnetic resonance imaging. Fatigue in MS is associated with excessive daytime sleepiness and autonomic dysfunction. Recently it has been reported that the wakefulness-promoting drug modafinil may relieve fatigue in MS patients and ameliorate the associated cognitive difficulties. However, it is not clear to what extent the anti-fatigue effect of modafinil may be related to its alerting and sympathetic activating effects. We addressed this question by comparing three groups of subjects, MS patients with fatigue, MS patients without fatigue and healthy controls, matched for age and sex, on measures of alertness (self-ratings on the Epworth and Stanford Sleepiness Scales and on a battery of visual analogue scales; critical flicker fusion frequency; Pupillographic Sleepiness Test; choice reaction time) and autonomic function (systolic and diastolic blood pressure, heart rate, pupil diameter), and by examining the effect of a single dose (200 mg) of modafinil on these measures. MS patients with fatigue, compared with healthy controls, had reduced level of alertness on all the tests used; MS patients without fatigue did not differ from healthy controls. MS patients with fatigue had a reduced level of cardiovascular sympathetic activation compared to the other two groups. Modafinil displayed alerting and sympathomimetic effects in all three groups of subjects. As fatigue in MS is associated with reduced levels of alertness and sympathetic activity, modafinil may exert its anti-fatigue effect in MS by correcting these deficiencies. The anti-fatigue effect of modafinil may reflect the activation of the noradrenergic locus coeruleus (LC), since there is evidence that this wakefulness-promoting nucleus is damaged in MS, and that modafinil, probably via the dopaminergic system, can stimulate the LC. This article is part of a Special Issue entitled 'Cognitive Enhancers'.
 ...
PMID:Association of a deficit of arousal with fatigue in multiple sclerosis: effect of modafinil. 2276 94

Rapid ascent to high altitude causes illness and fatigue, and there is a demand for effective acute treatments to alleviate such effects. We hypothesized that increased oxygen delivery to the tissue using a combination of a hypertensive agent and an endothelin receptor A antagonist drugs would limit exercise-induced fatigue at simulated high altitude. Our data showed that the combination of 0.1 mg/kg ambrisentan with either 20 mg/kg ephedrine or 10 mg/kg methylphenidate significantly improved exercise duration in rats at simulated altitude of 4,267 m, whereas the individual compounds did not. In normoxic, anesthetized rats, ephedrine alone and in combination with ambrisentan increased heart rate, peripheral blood flow, carotid and pulmonary arterial pressures, breathing rate, and vastus lateralis muscle oxygenation, but under inspired hypoxia, only the combination treatment significantly enhanced muscle oxygenation. Our results suggest that sympathomimetic agents combined with endothelin-A receptor blockers offset altitude-induced fatigue in rats by synergistically increasing the delivery rate of oxygen to hypoxic muscle by concomitantly augmenting perfusion pressure and improving capillary conductance in the skeletal muscle. Our findings might therefore serve as a basis to develop an effective treatment to prevent high-altitude illness and fatigue in humans.
...
PMID:Anti-hypotensive treatment and endothelin blockade synergistically antagonize exercise fatigue in rats under simulated high altitude. 2496 Jan 87

3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a unique drug, sharing properties of hallucinogens and stimulants. The acute effects of empathy, euphoria, and excitement for which it is used recreationally can make it overwhelmingly distracting for the user in the context of driving. This review considers the chemistry, synthesis, analysis, pharmacology, pharmacokinetics, and documented effects of MDMA on cognitive and psychomotor skills important to driving. Laboratory studies show that users do experience cognitive impairments, and may also act more impulsively while under the influence of the drug's sympathomimetic effects. Psychomotor impairment may occur with elevated doses or after repeated administration, and residual psychomotor impairment during the "coming-down" phase may be compounded by fatigue, dehydration, combined drug use, or other confounding factors. There is growing anecdotal information providing evidence of MDMA-impaired driving, and it is evident that many users recognize and attempt to mitigate the effects by delaying driving until the acute affects have dissipated. The drug inevitably may affect a subject's judgment and ability to properly assess their fitness to drive also. Blood concentrations in MDMA-impaired drivers suggest that this impairment can be caused by normal patterns of recreational use, and MDMA use should be considered inconsistent with safe driving immediately following ingestion, and for up to a day or longer following use.
...
PMID:3,4-Methylenedioxymethamphetamine - Effects on Human Performance and Behavior. 2625 92

In the past two decades, the synthetic style and fashion drug "crystal meth" ("crystal", "meth"), chemically representing the crystalline form of the methamphetamine hydrochloride, has become more and more popular in the United States, in Eastern Europe, and just recently in Central and Western Europe. "Meth" is cheap, easy to synthesize and to market, and has an extremely high potential for abuse and dependence. As a strong sympathomimetic, "meth" has the potency to switch off hunger, fatigue and, pain while simultaneously increasing physical and mental performance. The most relevant side effects are heart and circulatory complaints, severe psychotic attacks, personality changes, and progressive neurodegeneration. Another effect is "meth mouth", defined as serious tooth and oral health damage after long-standing "meth" abuse; this condition may become increasingly relevant in dentistry and oral- and maxillofacial surgery. There might be an association between general methamphetamine abuse and the development of osteonecrosis, similar to the medication-related osteonecrosis of the jaws (MRONJ). Several case reports concerning "meth" patients after tooth extractions or oral surgery have presented clinical pictures similar to MRONJ. This overview summarizes the most relevant aspect concerning "crystal meth" abuse and "meth mouth".
 ...
PMID:Meth Mouth-A Growing Epidemic in Dentistry? 2956 35

Adrafinil, a new molecule identified by a French drug company, L. Lafon Ltd, in 1974, was found to cause a significant dose-dependent increase in motor activity in mice, without exerting peripheral sympathomimetic effects. As early as 1977-78, Michel Jouvet prescribed adrafinil to narcoleptic patients, but without consistent results. Meanwhile the kinetics of adrafinil led to the identification of an active metabolite, modafinil. In 1983, Jouvet and Bastuji prescribed modafinil to narcoleptic and idiopathic hypersomnia patients and obtained a significant decrease of excessive daytime sleepiness and sleep attacks in a majority of patients. L. Lafon Ltd was initially not interested in developing this molecule for market however, thanks to Jouvet's insistance, it decided to start clinical trials in both healthy volunteers and narcoleptic patients as well as conduct animal studies. Results were excellent and led to the use of modafinil by the French army during the Gulf War in January-February 1991, as well as to the official registration of the drug in France in 1992. Subsequent multicenter controlled clinical trials in North America confirmed the findings in Europe. Modafinil was later used to treat sleepiness, somnolence and fatigue in a large number of medical conditions.
 ...
PMID:Modafinil: its discovery, the early European and North American experience in the treatment of narcolepsy and idiopathic hypersomnia, and its subsequent use in other medical conditions. 3017 15

Orthostatic hypotension (OH) is a common non-motor feature of Parkinson's disease that may cause unexplained falls, syncope, lightheadedness, cognitive impairment, dyspnea, fatigue, blurred vision, shoulder, neck, or low-back pain upon standing. Blood pressure (BP) measurements supine and after 3 minutes upon standing screen for OH at bedside. The medical history and cardiovascular autonomic function tests ultimately distinguish neurogenic OH, which is due to impaired sympathetic nerve activity, from non-neurogenic causes of OH, such as hypovolemia and BP lowering drugs. The correction of non-neurogenic causes and exacerbating factors, lifestyle changes and non-pharmacological measures are the cornerstone of OH treatment. If these measures fail, pharmacological interventions (sympathomimetic agents and/or fludrocortisone) should be introduced stepwise depending on the severity of symptoms. About 50% of patients with neurogenic OH also suffer from supine and nocturnal hypertension, which should be monitored for with in-office, home and 24 h-ambulatory BP measurements. Behavioral measures help prevent supine hypertension, which is eventually treated with non-pharmacological measures and bedtime administration of short-acting anti-hypertensive drugs in severe cases. If left untreated, OH impacts on activity of daily living and increases the risk of syncope and falls. Supine hypertension is asymptomatic, but often limits an effective treatment of OH, increases the risk of hypertensive emergencies and, combined with OH, facilitates end-organ damage. A timely management of both OH and supine hypertension ameliorates quality of life and prevents short and long-term complications in patients with Parkinson's disease.
 ...
PMID:Management of Orthostatic Hypotension in Parkinson's Disease. 3271 19


<< Previous 1 2 3