Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the study was to ascertain whether the new hypnotic, zopiclone, was likely to produce rebound problems after short-term use, in comparison with placebo and a standard hypnotic, temazepam, and whether tapering the dosage lessened any such effects. Ten normal v olunteer subjects were administered 5 treatment sequences, each lasting 4 weeks, using a balanced design, with at least 2 weeks between sequences. The treatment sequences were: (table: see text) Each drug was given at night before retiring to bed. Daily ratings comprised a Sleep Questionnaire, Mood Rating Scales, the Spielberger State Anxiety Inventory and Bodily Symptom Scales. Both drugs improved quality of sleep but their discontinuation was followed by some worsening which was postponed but not avoided by halving the dosage for a week. Speed of, and feeling on, awakening showed discontinuation effects with temazepam but not with zopiclone. Zopiclone was associated with feelings of being troubled, tense, antagonistic and bored whereas temazepam produced drowsiness, clumsiness, dreaminess and sadness. Some increase in these ratings was noted after stopping temazepam and these were less after having the dosage. Zopiclone was associated with minimal such effects. For bodily symptoms, zopiclone produced some headache, a metallic taste, and some blurring of vision; temazepam induced nausea, memory impairment and pins and needles. Withdrawal effects on bodily symptom ratings were inconsistent and not affected by tapering off the dose. In conclusion, the administration of zopiclone tends to be associated with some dysphoric effects, temazepam with sedation. Rebound effects are minimal with zopiclone and reducing the dosage gradually does not seem necessary.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Subjective effects during administration and on discontinuation of zopiclone and temazepam in normal subjects. 288 82

Suriclone selectively displaces benzodiazepines from their binding sites but is structurally unrelated to benzodiazepines. Neurologic effects of suriclone were compared to those of diazepam in 54 subjects in a sequential, double-blind, single dose, randomized study (placebo; diazepam 10 mg; suriclone 0.2, 0.4, 0.6, or 0.8 mg). Data were collected on-line by microcomputer. Suriclone 0.2 mg did not differ from placebo. Suriclone 0.4 mg and 0.6 mg did not differ from diazepam 10 mg. Suriclone 0.8 mg caused significantly more decrement than diazepam 10 mg (p less than 0.05) in manual tracking, force platform stability, and Heath rail walking and in total severity of symptoms. Suriclone 0.8 mg caused nausea (p = 0.02), clumsiness (p = 0.02), and loss of balance (p = 0.01) more frequently than diazepam 10 mg. Suriclone 0.8 mg produced symptoms and signs qualitatively and quantitatively different from diazepam 10 mg, such as vomiting, unusual ocular movement effects, and difficulty walking. Possibly the differences in CNS drug binding for anxiolytics are associated with clinical differences in toxicity.
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PMID:Comparative neurologic effects of diazepam and suriclone, a cyclopyrrolone anxiolytic. 289 78

Benzodiazepines are used as hypnotics to reduce anxiety and give a good night's sleep on the night prior to surgery. In a double-blind procedure, patients were given either lorazepam (2 mg or 4 mg), lormetazepam (1 mg or 2 mg), nitrazepam 10 mg or placebo. Measures were taken of sleep, anxiety, memory and after-effects. There was no evidence that the drugs reduced anxiety, nor evidence of amnesia. Quality and length of sleep was shown to be better for nitrazepam (P less than 0.05), lorazepam 2 mg (P less than 0.05) and lorazepam 4 mg (P less than 0.01), compared with placebo. However, significantly higher ratings of clumsiness and confusion as after-effects were found with nitrazepam (P less than 0.05), and clumsiness (P less than 0.005), slurred speech and blurred vision (P less than 0.01), sleepiness, nausea, weakness and confusion (P less than 0.05) with lorazepam 4 mg. It was concluded that lorazepam 2 mg produced the greatest net benefit.
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PMID:A double-blind comparison between nitrazepam, lorazepam, lormetazepam and placebo as preoperative night sedatives. 290 15

Three placebo-controlled double-blind and crossover trials were carried out to analyze the effects of oral yohimbine (YOH) 0.8 mg/kg on mood and performance in 16 healthy students. Subjective assessments (visual analogue scales, side-effects on questionnaire) and objective measurements (digit symbols, flicker fusion, tapping, heterophoria) were done at baseline, and post treatment. YOH shifted the healthy subjects' mood towards feeling panicked, elevated systolic blood pressure and plasma prolactin concentrations, reduced digit symbol substitution, and induced drowsiness and passiveness. Caffeine (CAF) 10 mg/kg raised plasma cortisol and rendered the subjects slightly panicked. Muzziness, clumsiness, tremor, chills and nausea were common after both YOH and CAF. Diazepam (DZ) 0.3 mg/kg given at 60 min antagonized some effects of CAF but failed to antagonize YOH. Clonidine (CLO) 100 micrograms counteracted YOH effects on blood pressure but less the subjective and hormonal effects. CLO 200 micrograms partly antagonized the pressor, sedative but not the hormonal responses of YOH. DZ counteracted YOH effects on plasma cortisol on panic but not on other subjective measures or plasma prolactin. Since CLO did not abolish YOH-induced prolactin increase, it is suggested that these effects of YOH are mediated not only via adrenergic alpha 2-receptors; other mechanisms made important contributions.
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PMID:Anxiogenic effect of yohimbine in healthy subjects: comparison with caffeine and antagonism by clonidine and diazepam. 315 10

Forty-seven climbers participated in a double-blind, randomized trial comparing acetazolamide 250 mg, dexamethasone 4 mg, and placebo every eight hours as prophylaxis for acute mountain sickness during rapid, active ascent of Mount Rainier (elevation 4,392 m). Forty-two subjects (89.4 percent) achieved the summit in an average of 34.5 hours after leaving sea level. At the summit or high point attained above base camp, the group taking dexamethasone reported less headache, tiredness, dizziness, nausea, clumsiness, and a greater sense of feeling refreshed (p less than or equal to 0.05). In addition, they reported fewer problems of runny nose and feeling cold, symptoms unrelated to acute mountain sickness. The acetazolamide group differed significantly (p less than or equal to 0.05) from other groups at low elevations (1,300 to 1,600 m), in that they experienced more feelings of nausea and tiredness, and they were less refreshed. These drug side effects probably obscured the previously established prophylactic effects of acetazolamide for acute mountain sickness. Separate analysis of an acetazolamide subgroup that did not experience side effects at low elevations revealed a prophylactic effect of acetazolamide similar in magnitude to the dexamethasone effect but lacking the euphoric effects of dexamethasone. This study demonstrates that prophylaxis with dexamethasone can reduce the symptoms associated with acute mountain sickness during active ascent and that acetazolamide can cause side effects that may limit its effectiveness as prophylaxis against the disease.
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PMID:A randomized trial of dexamethasone and acetazolamide for acute mountain sickness prophylaxis. 333 64

Oral amantadine 100 mg and bromocriptine 2.5 + 2.5 mg, alone and in combination with ethanol (1 g/kg), were investigated in two placebo-controlled, double-blind and cross-over trials. In the first trial the psychomotor effects of amantadine and bromocriptine were compared to those of placebo, and in the second trial ethanol was added to the treatment. Bromocriptine lowered serum prolactin levels, thus confirming its absorption. Amantadine and bromocriptine alone had no psychomotor effects but unpleasant sensations, nausea and dizziness were reported after bromocriptine. Ethanol impaired performance in terms of impaired coordinative and reactive skills, lowered tapping speed, prolonged critical flicker interval and reduced gaze nystagmus angle (P less than 0.05 to 0.001; two-way ANOVA). Subjectively, ethanol induced mental slowness, clumsiness and impairment of performance (P less than 0.05 to 0.001). Amantadine and bromocriptine failed to counteract any of these ethanol-induced changes. It is concluded that in man, an acute dopaminergic activation by amantadine or bromocriptine does not significantly modify the psychomotor effects of ethanol.
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PMID:Failure of amantadine and bromocriptine to counteract alcoholic inebriation in man. 650 9

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

Neurovestibular symptoms experienced by astronauts in the post-flight period were examined using data from medical debriefs contained in the NASA Longitudinal Study of Astronaut Health database. Ten symptoms were identified (clumsiness, difficulty concentrating, persisting sensation aftereffects, nausea, vomiting, vertigo while walking, vertigo while standing, difficulty walking a straight line, blurred vision, and dry heaves), of which eight were crossed with twelve demographic parameters (mission duration, astronaut gender, age, one-g piloting experience, previous space flight experience, g-suit inflation, g-suit deflation, in-flight space motion sickness, in-flight exercise, post-flight exercise, mission role, fluid loading). Three symptoms were experienced by a majority of subjects, and another two by more than a quarter of the subjects. Intensity of the symptoms was mild, suggesting that they are unlikely to pose a risk to the crew during landing and the post-flight period. Seven of the symptoms and eight of the parameters under study were found to be significantly associated with each other.
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PMID:Neurovestibular symptoms following space flight. 1475 12

Recently there has been a resurgence in the utilization of ketamine, a unique anaesthetic, for emergency procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the small clinic setup of rural Nepal. One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the Orthopaedic & Trauma Clinic at Janakpurdham were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of less than two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphonic reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures at our institution. Therefore, it was ideal for small clinic in our setup.
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PMID:Sedation with ketamine: a safe and effective anaesthetic agent for children in the developing world. 1658 65

Episodic ataxia type 1 (EA1) is a K(+) channelopathy characterized by a broad spectrum of symptoms. Generally, patients may experience constant myokymia and dramatic episodes of spastic contractions of the skeletal muscles of the head, arms, and legs with loss of both motor coordination and balance. During attacks additional symptoms may be reported such as vertigo, blurred vision, diplopia, nausea, headache, diaphoresis, clumsiness, stiffening of the body, dysarthric speech, and difficulty in breathing. These episodes may be precipitated by anxiety, emotional stress, fatigue, startle response or sudden postural changes. Epilepsy is overrepresented in EA1. The disease is inherited in an autosomal dominant manner, and genetic analysis of several families has led to the discovery of a number of point mutations in the voltage-dependent K(+) channel gene KCNA1 (Kv1.1), on chromosome 12p13. To date KCNA1 is the only gene known to be associated with EA1. Functional studies have shown that these mutations impair Kv1.1 channel function with variable effects on channel assembly, trafficking and biophysics. Despite the solid evidence obtained on the molecular mechanisms underlying EA1, how these cause dysfunctions within the central and peripheral nervous systems circuitries remains elusive. This review summarizes the main breakthrough findings in EA1, discusses the neurophysiological mechanisms underlying the disease, current therapies, future challenges and opens a window onto the role of Kv1.1 channels in central nervous system (CNS) and peripheral nervous system (PNS) functions.
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PMID:New insights into the pathogenesis and therapeutics of episodic ataxia type 1. 2634 8


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