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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of alpha 2-adrenoceptor agonists and antagonists on saccadic eye movements were studied in normal volunteers using the agonist clonidine and the antagonist idazoxan. Changes in blood pressure, heart rate, and several psychological self-ratings were also recorded. Clonidine produced marked slowing of peak saccade velocity, acceleration and deceleration, with deceleration affected more than acceleration, but had no effect on saccade error or latency measurements. In contrast, most saccade parameters were not altered by idazoxan, although fatigue effects were eliminated. Blood pressure, heart rate, and self ratings of alertness were increased by idazoxan and reduced by clonidine, with opposite effects noted on sedation self-ratings. There were no correlations between the clonidine-induced changes in saccade parameters and changes in self-ratings. Although the slowing of some saccade parameters by clonidine may imply that alpha 2-adrenoceptors are involved in control of saccades, it may also be due to sedation. Although alpha 2-adrenoceptor antagonists may abolish fatigue effects, they cannot increase them over baseline values.
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PMID:Pharmacology of saccadic eye movements in man. 2. Effects of the alpha 2-adrenoceptor ligands idazoxan and clonidine. 168 14

In a prospective, double-blind comparison, we assessed the efficacy of transdermal clonidine with that of chlordiazepoxide in the treatment of moderately severe acute alcohol withdrawal syndrome. While having significant withdrawal symptoms, 50 hospitalized men were randomly assigned to receive either transdermal clonidine or chlordiazepoxide over a 4-day study period. Outcome was evaluated daily, medically and psychiatrically, using both objective and subjective measurements for dependent variables. No patient in either study group had seizures or progression to delirium tremens. The group receiving transdermal clonidine had a more significant response globally for the signs and symptoms of alcohol withdrawal, as measured by the Alcohol Withdrawal Assessment Scale. Also, clonidine more effectively lowered elevated systolic and diastolic blood pressure and heart rate. The core target symptom, anxiety, decreased significantly more in the patients receiving transdermal clonidine when measured by the Hamilton Anxiety Rating Scale and its subscale for somatic anxiety. Cognitive function responded equally in both study populations. Clonidine-treated patients reported less diarrhea, dizziness, headache and fatigue, and the chlordiazepoxide-treated patients reported less nausea and vomiting. We conclude that transdermal clonidine is effective treatment for the acute alcohol withdrawal syndrome.
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PMID:Transdermal clonidine versus chlordiazepoxide in alcohol withdrawal: a randomized, controlled clinical trial. 200 May 17

Sixteen of 22 elderly male patients (aged 60-74 years) who had previously taken only hydrochlorothiazide 50 mg completed a study evaluating the safety, efficacy, and tolerability of 12-20 weeks of transdermal clonidine (Catapres TTS) as monotherapy for mild hypertension. Thirteen of the sixteen patients (81%) responded to transdermal clonidine which was begun after 28 days of placebo. Five patients discontinued transdermal clonidine therapy because of intolerable skin irritation, and one because of daytime fatigue. Clonidine caused none of the metabolic effects we observed with hydrochlorothiazide: no change in serum potassium, uric acid, cholesterol, or triglyceride. Eleven of the 22 patients (50%) who began the study experienced a skin reaction under the transdermal clonidine patch. The incidence of dry mouth and fatigue in patients using transdermal clonidine was dose-related and similar to reports of dry mouth and fatigue in patients taking oral clonidine tablets. Rebound hypertension occurred in one patient upon withdrawal of transdermal clonidine. There was no effect of transdermal clonidine or hydrochlorothiazide on cognitive function or emotional state tested with three questionnaires. Overall, transdermal clonidine, in various doses, was as effective as hydrochlorothiazide in elderly male hypertensive patients. The effectiveness of both was inversely proportional to the level of untreated blood pressure. The high incidence of skin reactions limited prolonged use of transdermal clonidine in our patients.
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PMID:Transdermal clonidine compared with hydrochlorothiazide as monotherapy in elderly hypertensive males. 271 69

1. Three double-blind studies in young normotensive male volunteers were carried out: a study in ten awake subjects, comparing guanfacine 2.0 and 4.0 mg with clonidie 0.15 and 0.30 mg and placebo; and two polygraphic sleep studies each with six subjects, comparing guanfacine 1.0 and 2.0 mg with placebo, and clonidine 0.15 and 0.30 mg with placebo, respectively. 2. In awake subjects, both drugs reduced systolic blood pressure without significantly altering diastolic blood pressure, pulse rate and objective performance parameters. 'Side-effects' such as tiredness, decreased inclination to work, and dryness of the mouth were somewhat more frequent after the higher clonidine dose than after both doses of guanfacine, and peaked 2 h after clonidine but only 4-6 h after guanfacine. 3. Clonidine 0.15 and 0.30 mg given in the evening was followed by a substantial and dose-dependent reduction in rapid eye movement (REM) sleep. Guanfacine 1.0 mg did not alter REM sleep and 2.0 mg of guanfacine had less effect than both doses of clonidine in this respect. Clonidine's effect on REM sleep began after about 2 h, whereas guanfacine's action on REM sleep began 5 h after the dose. 4. Guanfacine and clonidine possess a qualitatively similar pattern of activity with regard to the parameters studied; but the central effects are less pronounced and occur later after guanfacine than after clonidine in equiactive doses.
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PMID:Central effects of guanfacine and clonidine during wakefulness and sleep in healthy subjects. 699 71

Traditional centrally acting antihypertensives have been associated with a high incidence of adverse effects and are no longer recommended as first-line therapy. The newer imidazoline receptor agonists must overcome this reputation if they are to gain recognition as potential first-line agents for hypertension. Methyldopa, a centrally acting alpha(2)-agonist, is characterized by a number of serious adverse reactions that limit its use. Although unpredictable idiosyncratic or hypersensitivity reactions are uncommon, these include hepatitis, myocarditis, and hemolytic anaemia. Less serious problems such as abnormal liver function tests, positive Coombs test, drug-induced fever, and pancreatitis also occur. Central side effects include drowsiness, fatigue, lethargy, sedation, depression, psychotic reactions, nasal stuffiness, impotence, and exacerbation of Parkinsonism. In hypertensive men, methyldopa is less well tolerated than either captopril or propranolol, and up to 20% of patients discontinue therapy because of adverse effects. Clonidine acts primarily as an alpha(2)-agonist but also acts as an agonist at imidazoline receptors in the rostroventrolateral medulla. It is equipotent to most other antihypertensives but is considerably less well-tolerated in comparative trials. The principal adverse effects of clonidine are drowsiness, sedation, lethargy and dry mouth. Reserpine acts primarily by depleting central catecholamine neurotransmitter stores. It was very extensively used in early hypertension trials, but its central side effects of sedation, nasal stuffiness, and severe depression are now considered so undesirable that the drug is seldom prescribed. The imidazoline (I1) agonists moxonidine and rilmenidine act selectively and have very little central alpha(2)-agonist activity. In comparative studies against placebo and other reference antihypertensives, the only adverse effect consistently associated with these drugs was dry mouth (approximate placebo-corrected incidence 10%). Sedation was not pronounced. Withdrawal syndromes are complex pathophysiologic processes and occur with a variety of antihypertensive drugs. Cessation of therapy with clonidine and, to a lesser extent, methyldopa may result in a severe withdrawal syndrome characterized by restlessness, sweating, anxiety, tremor, palpitations, and headache. There may be a rapid rise in blood pressure, often with a true "rebound" to higher than pretreatment levels. Plasma and urinary catecholamine levels are increased, and fatalities have been reported. It is important to stress that such a syndrome has not been recorded, in animal or human studies, with either moxonidine or rilmenidine.
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PMID:Aspects of tolerability of centrally acting antihypertensive drugs. 887 99

In this double-blind placebo controlled study the preoperative cardiovascular and metabolic effects of intramuscular (i.m.) clonidine and midazolam are assessed. Forty-five ASA Grade I patients (n = 15 per group) undergoing plastic surgical procedures were randomly allocated to receive either placebo, clonidine 4 micrograms kg-1 or midazolam 70 micrograms kg-1. Drugs were administered into the deltoid muscle approximately 90 min prior to the scheduled induction of anaesthesia. The metabolic measurements were performed using an indirect calorimetry device. Heart rate and blood pressure were measured noninvasively. Pre-operative subjective anxiety, dryness of mouth and tiredness were assessed using visual analogue scales (VAS). Clonidine increased subjective tiredness significantly more than placebo. Clonidine also induced moderate decreases in blood pressure and heart rate. Oxygen consumption (VO2), CO2 production and energy expenditure (EE) decreased significantly after clonidine and midazolam. The decrease in VO2 and EE was maximally 11-14% on average from the base-lines after clonidine and midazolam. These effects were of longer duration after clonidine and lasted until the end of the 90 min study period. In conclusion, both clonidine and midazolam are effective as a means of decreasing pre-operative VO2 and EE.
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PMID:Cardiovascular and metabolic responses to clonidine and midazolam premedication. 908 19

alpha-Agonists are a relatively old class of medications, the topical use of which lowers eye pressure. Clonidine was introduced for this use in 1966, brimonidine in 1974, and apraclonidine in 1978. Initial short-term attempts to use clonidine were complicated by problems with systemic hypotension. Apraclonidine is more polar and less lipophilic than clonidine. This probably allows less penetration into both the posterior segment of the eye and systemic circulation, allowing for an excellent therapeutic index. The prophylactic use of apraclonidine (1% and 0.5%) has dramatically changed the safety profile for many anterior segment laser procedures, cataract surgery, and vitrectomy. The role of alpha-agonists in the chronic treatment of glaucoma is still uncertain. Potential benefits of additional lowering of intraocular pressure must be weighed against the following potential disadvantages: tachyphalaxsis, posterior segment vasoconstriction, psychologic depression and fatigue, syncope and systemic hypotension, and a topical allergy-like syndrome.
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PMID:The role of alpha-agonists in glaucoma therapy. 1016 56

Although originally developed for the treatment of hypertension, alpha(2)-agonists have been used to treat Tourette's syndrome, attention-deficit hyperactivity disorder (ADHD), developmental disorders and substance abuse for nearly three decades. Based on studies of clonidine, alpha(2)-agonists were presumed to reduce arousal by decreasing the firing of noradrenaline neurons in locus ceruleus. Accumulated preclinical evidence indicates that guanfacine has features in common with clonidine, in addition to other pharmacological effects. Clonidine binds to the three subtypes of alpha(2)-receptors, A, B and C, whereas guanfacine binds more selectively to alpha(2A)-receptors, which appears to enhance prefrontal function. Several reports on the use of the alpha(2)-agonists show improvements in children with ADHD and improvements in hyperactivity, impulsiveness and inattention in children with tic disorders and pervasive developmental disorders. Both clonidine and guanfacine are associated with sedation, fatigue and somnolence. Reductions in heart rate and blood pressure are modest and rarely lead to discontinuation of treatment across these trials.
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PMID:Alpha-2 adrenergic agonists in children with inattention, hyperactivity and impulsiveness. 1962 77

A 53-year-old female presented with rheumatoid arthritis and osteoporosis. Additional conditions and symptoms included Raynaud syndrome, fatigue, irritable bowel syndrome associated constipation (IBS-C), gastroesophageal reflux (GERD), menopausal symptoms, chronic urinary tract and upper respiratory infections, and weight gain. She was taking Arthrotec (a combination of diclofenac and misoprostol - for pain and inflammation), Fosamax Plus D (alendronate with vitamin D3 - recently prescribed because of low bone density), and Catapres (clonidine - for menopausal symptoms). Against the advice of her rheumatologist, she had recently discontinued taking Plaquenil (hydroxychloroquine), methotrexate, and prednisone due to significant side effects. Lab tests to identify underlying imbalances and to direct treatment were ordered. Treatment included dietary, nutritional, hormonal, and mind/body support. After one year of therapy, the patient experienced improvement with all of her presenting conditions and symptoms, which enabled her to discontinue several medications. She became versed in identifying and avoiding the environmental triggers of her disease, including foods (dairy, wheat, eggs, and soy), molds, and emotional stress. Antinuclear antibodies were normalized. She experienced a 7.5-percent improvement in left trochanteric bone density - comparable to bisphosphonate therapy. Mild improvements were also noted in the spine and bilateral femoral neck.
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PMID:A case report of a 53-year-old female with rheumatoid arthritis and osteoporosis: focus on lab testing and CAM therapies. 2195 Oct 26

Clonidine has been used off-label in children and adolescents with attention deficit and hyperactivity disorders (ADHD) with or without comorbidities. Clonidine extended-release was recently approved by the US Food and Drug Administration for ADHD in children. This review evaluates the efficacy and safety of clonidine extended-release and clonidine in children and adolescents with ADHD. A search of the Medline database and clinical trials register from 1996-2011 yielded ten clinical trials for critical evaluation of efficacy and safety. Eight of the ten trials reviewed were double-blinded and placebo-controlled. Nine of the ten trials utilized multiple outcome measures. Both clonidine extended-release and clonidine, as monotherapy or adjunctive therapy, were reported to be efficacious in treating ADHD symptoms in children and adolescents with or without comorbid disorders in nine of the ten clinical trials. One study showed clonidine to be ineffective in improving performance of a single task, at a specific point in time, in a small number of subjects. All of the studies that evaluated safety reported clonidine and clonidine extended-release to be well tolerated. The side effects of clonidine included somnolence, fatigue, headache, bradycardia, hypotension, and clinically insignificant electrocardiographic changes. However, there are historical anecdotal reports of serious cardiac side effects, including death in cases with other risk factors. None of the studies compared clonidine extended-release with clonidine in subjects with ADHD. Therefore, it is not clear whether clonidine extended-release is advantageous over clonidine, with regard to either efficacy or safety. It is equally unclear whether clonidine or clonidine extended-release is more efficacious in treating ADHD in subjects with comorbid disorders than in those without comorbidities. All the studies reviewed had limitations in their designs and methods. Clonidine and clonidine extended-release could be efficacious and safe for the treatment of ADHD both as monotherapy and as adjunctive therapy with stimulant medications in selected patients. There is a need for clinical trials to determine the long-term efficacy and safety of treatment with clonidine and clonidine extended-release in patients with ADHD.
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PMID:Safety and efficacy of clonidine and clonidine extended-release in the treatment of children and adolescents with attention deficit and hyperactivity disorders. 2460 Feb 80


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