Biomedical subjects

A N Nicholson

Publications and source records attributed to A N Nicholson.

At least 55 records · Page 3Linked to original sources

PubMed1986

Behavioural responses to diazepam of drug-naive and experienced monkeys (Macaca mulatta).

Effects of 5 mg/kg diazepam given once a week for several weeks to drug-naive and drug-experienced monkeys were studied on a spatial delayed-alternation task. In both groups response latency was increased and the number of correct responses was reduced. The effects were consistent over weeks in the experienced monkeys, but in the naive monkeys there were greater initial effects on response latency and on repeat errors, and these lessened over 2-3 weeks. Thereafter, effects resembled those observed in the experienced group. Results are discussed in terms of the possible factors involved in the development and persistence of tolerance to benzodiazepines.

Animals↗

PubMed1986

Antihistamines: impaired performance and the tendency to sleep.

The central effects of various antihistamines were studied using a variety of tests of performance, including visuo-motor co-ordination and dynamic visual acuity, as well as paper and pencil tests and critical flicker fusion. The possible relationship between performance and sedation was also studied using digit symbol substitution and latencies to drowsy sleep. There was high degree of correlation between drowsiness, as indicated by the relative ease with which individuals fell asleep over the day, and impaired performance, but it was not possible to establish the relationship for each time of the day. These findings lend some support to the suggestion that impaired performance with antihistamines may be a non-specific effect of sedation.

Adult↗

PubMed1986

5-Hydroxytryptamine and noradrenaline uptake inhibition: studies on sleep in man.

Effects of an inhibitor of the uptake of noradrenaline (maprotiline, 75 and 150 mg) and two inhibitors of the uptake of 5-hydroxytryptamine (zimelidine, 100 and 200 mg; indalpine, 25 and 50 mg) on sleep were studied in healthy man. Maprotiline reduced the duration of rapid eye movement (REM) sleep and increased the duration of stage 2 sleep, and there was evidence of sedation the next day. Zimelidine and indalpine reduced the duration of REM sleep, but also reduced the total sleep time and increased wakefulness and stage 1 (drowsy) sleep. It is suggested that in acute studies, the effects of inhibition of uptake on sleep are likely to arise from presynaptic inhibition of release of transmitter, although other mechanisms cannot be excluded. Suppression of REM sleep is believed to be due to the balance between cholinergic and monoaminergic influences being disturbed rather than a specific effect arising from the modulation of a particular transmitter.

Adolescent↗

PubMed1986

Modulation of catecholamine transmission and sleep in man.

The effect of modulation of catecholamine transmission on sleep in man was studied using mianserin (20 and 40 mg) and nomifensine (50 and 100 mg). It is suggested that reduced wakefulness induced by mianserin during sleep is primarily related to postsynaptic antagonism of alpha adrenoceptors, though a possible synergistic effect with antagonism of histamine H1 receptors cannot be excluded, while increased wakefulness with nomifensine is related to inhibition of the uptake of catecholamines and/or direct or indirect dopaminergic activity. The reduction in rapid eye movement (REM) sleep with both drugs is believed to be a non-specific effect which arises from a disturbance of the balance between monoaminergic and cholinergic influences.

Adult↗

PubMed1986

Transient insomnia and rapidly eliminated hypnotics.

The effects of an ultra-rapidly eliminated hypnotic (midazolam 7.5-15.0 mg; mean elimination half-life approximately 2 h) and a rapidly eliminated hypnotic (brotizolam 0.125-0.25 mg; mean elimination half-life approximately 5 h) were studied on transient insomnia induced by sleeping in a reclining seat. Rest in the seat did not lead to delay in sleep onset, but there was increased wakefulness and drowsy sleep and less REM sleep. There were no differences in wakefulness or drowsiness between sleep with drugs in the seat and with placebo in bed, but with midazolam, though not with brotizolam, there was a reduction in REM sleep less than or equal to 300 min after sleep onset. Ultra-rapidly and rapidly eliminated compounds used in the management of transient insomnia should be given in doses that are as free as possible from central nervous system depression as indicated by suppression of REM sleep during the early part of the night. Low doses of ultra-rapidly eliminated drugs are indicated for sleep-onset insomnia and for short periods of sleep, while rapidly eliminated hypnotics with elimination half-lives of approximately 5 h have the potential to sustain sleep free of residual effects.

Adolescent↗

PubMed1986

Modulation of delta activity by hypnotics in middle-aged subjects: studies with a benzodiazepine (flurazepam) and a cyclopyrrolone (zopiclone).

Period crossing analysis was used to study the effects of flurazepam (30 mg) and zopiclone (5, 7.5, and 10 mg) on delta wave activity (0.5-2.0 Hz) during the first 4 h of sleep in middle-aged subjects. The drugs do not affect the visual scoring of slow wave sleep in middle age, but modification of delta activity does occur. Mean amplitude of delta wave activity over the 4-h period was reduced by both drugs, while the total number of delta waves and their mean period increased. The number of high-amplitude delta waves (greater than 60 microV) was decreased by the drugs, and those of low amplitude (10-60 microV) increased. Power in the frequency band 1.2-2.0 Hz was reduced.

Aging↗

PubMed1986

Effects of a mu-opioid receptor agonist (codeine phosphate) on visuo-motor coordination and dynamic visual acuity in man.

Effects of codeine (30, 60 and 90 mg) on visuo-motor coordination and dynamic visual acuity, together with critical flicker fusion, digit symbol substitution, complex reaction time and subjective assessments of mood, were studied from 0.75-2.0 h after ingestion by six healthy female adults. The study was double-blind and placebo controlled, and triprolidine (10 mg) was used as the active control. The effect on visuo-motor coordination was limited and was dose related and linear, and performance was altered on visuo-motor coordination with 60 and 90 mg codeine, and on dynamic visual acuity with 90 mg codeine (P less than 0.05). No other effect of codeine was detected. Modulated neuromuscular function is likely to be the common denominator of the changes in performance with codeine, though nausea, but not sedation, may be a contributory factor. It is possible that altered performance with codeine may involve interactions with different receptors than those which lead to sedation.

Adult↗

PubMed1986

Hypnotic activity of an imidazo-pyridine (zolpidem).

Effects of an imidazo-pyridine (zolpidem: 10, 20 and 30 mg) on overnight sleep and on performance the next day were studied in young adults and in middle aged individuals. The young adults were used particularly as an homogenous group to establish any possible adverse effects of the drug on sleep and on performance the next day, and the middle aged subjects with their less restful sleep were used to study efficacy. In the young adults zolpidem led to a marked increase in slow wave sleep with a reduction in stage 2 sleep. There were no significant changes in REM sleep, though there was a tendency for REM sleep to be delayed. In the middle aged there was a reduction in awake activity and drowsy sleep with an increase in stage 2 sleep. The latency to REM sleep was increased but the duration of REM sleep over the whole night was not reduced. Digit symbol substitution and a complex reaction time task were used to study performance, but there were no residual effects with zolpidem (9 h after ingestion). Zolpidem is likely to prove useful in the management of transient and short-term insomnia in healthy middle aged individuals when impaired performance the next day is to be avoided.

Adolescent↗

PubMed1986

Hypnotics and transient insomnia.

An hypnotic should be used only when there is evidence of sleep disturbance. The wide range of sleep disorders (e.g. delayed sleep onset or problems of sleep maintenance) and the added complication that the patient may be involved subsequently in skilled work demand that the pharmacokinetics of various hypnotics must be understood before the correct hypnotic can be chosen. Impaired performance is more severe and persists far longer with compounds that are slowly eliminated and with the use of higher doses. The particular situations of aircrew and mountaineers have been studied in detail. Caution must be exercised in the management of aircrew coping with irregularity of rest and work. Temazepam has been used for aircrew for over 10 years and the absence of adverse effects ensures that it remains the recommended hypnotic in this area of medical practice. The relationship of insomnia with the hypoxic environment is undetermined. To investigate this, sleep was studied in six individuals during an expedition to the Himalayas. At altitude, temazepam led to less wakefulness and to drowsy sleep--there were no prolonged sleep latencies.

Altitude↗

PubMed1986

Drugs and impaired performance.

Transient insomnia is known to occur in people who normally sleep well but whose sleeping pattern has been altered (e.g. by shift-work, intercontinental travel). The occasional use of an hypnotic is likely to be beneficial in these cases although, in the past, the problem of daytime sedation precluded the use of such drugs in certain occupations. Recent advances in therapeutics reflect the increasing interest in the impairment of performance and it is now recognized that both the nature and persistence of any effect must be determined. Two broad approaches are used at present: the laboratory study of isolated skills and some form of simulation such as car handling. There is, however, clear disagreement concerning the relevance of these two methods to the real-life situation and both have their limitations, so results must be interpreted with caution. In addition, an inability to demonstrate impaired performance does not necessarily mean that the drug is completely free from adverse effects, and different effects may be seen in a patient population compared with healthy volunteers because of variations in age, gender or concomitant drug therapy etc. It is fortunate that there are many drugs within a specific group which, though they have similar efficacy, have different effects on performance and so, accepting a limited impairment of performance, it should be possible for therapy to be suited to the day-to-day needs of any individual patient.

Arousal↗

PubMed1986

Irregularity of rest and activity: studies on circadian rhythmicity in man.

1. Rectal temperature, electrolyte excretion and performance were studied in young adults who followed an irregular pattern of work and rest for 9 days in an isolation unit. 2. In the analysis, effects evoked by the pattern of work and rest were separated from the oscillatory component, and rhythms for individual days were examined by the cosinor method. 3. During the schedule, rhythms no longer showed a period of exactly 24 h, and this effect was confirmed by studies using a repeated cycle of irregular work and rest and by studies using constant routines. 4. Temperature and urinary constituents differed in the strength and phase of their rhythms when corrected for evoked effects, as well as in the strength of the evoked effects themselves. 5. There was evidence of deterioration in performance during work periods which exceeded 9 h, but there was no evidence of progressive deterioration in performance over the 9 day schedule.

Activity Cycles↗

PubMed1986

Hypnotics. Their place in therapeutics.

Sleep disturbance has become a subject of serious study only over the past few years, but even so there is already an increasing awareness of the nature of insomnia and a greater understanding of the role which hypnotics should play in clinical medicine. An hypnotic may be used to shorten sleep onset when there is difficulty in falling asleep, to reduce nocturnal wakefulness, or to provide an anxiolytic effect during the next day when insomnia is accompanied by a marked element of anxiety. The purpose of an hypnotic is to meet one or more of these clinical problems; to ensure that the patient is given the most useful medication, consideration must be given to duration of activity. This depends on the absorption, distribution and elimination characteristics of the drug. It is now appreciated that the most appropriate use of hypnotics is in the individual with insomnia of recent origin. An hypnotic with the most relevant pharmacokinetic profile should be used for the shortest period of time and then only as required, while low doses will ensure freedom from adverse effects. The place of hypnotics in chronic insomnia remains less certain. Their careful use may well be of benefit, though it must be part of a well defined clinical strategy. Assessment of the patient is essential to identify any specific conditions which would impair sleep.

Acute Disease↗

PubMed1986

International cooperative study of aircrew layover sleep: operational summary.

The findings of this cooperative study of layover sleep have direct implications for flight operations. In the consensus view of the principal investigators, these can be divided into their relevance for eastward or westward flight. Eastward flight produced more sleep disruption than westward. Different sleep and scheduling strategies are recommended for each flight direction, and the importance of individual crewmember factors is discussed in relation to age and circadian type. Despite the limitations of this study with regard to trip simplicity and the baseline data, the results for each airline are highly consistent and should be applicable to a wide range of long-haul crewmembers and carriers.

Adult↗

PubMed1986

Nocturnal sleep and daytime alertness of aircrew after transmeridian flights.

The nocturnal sleep and daytime alertness of aircrew were studied by electroencephalography and the multiple sleep latency test. After a transmeridian flight from London to San Francisco, sleep onset was faster and, although there was increased wakefulness during the second half of the night, sleep duration and efficiency over the whole night were not changed. The progressive decrease in sleep latencies observed normally in the multiple sleep latency test during the morning continued throughout the day after arrival. Of the 13 subjects, 12 took a nap of around 1-h duration in the afternoon preceding the return flight. These naps would have been encouraged by the drowsiness at this time and facilitated by the departure of the aircraft being scheduled during the early evening. An early evening departure had the further advantage that the circadian increase in vigilance expected during the early part of the day would occur during the latter part of the return flight.

Adult↗

PubMed1986

Performance overnight in shiftworkers operating a day-night schedule.

Performance was measured during the day (0800-1700 hours) and during the night (1700-0800 hours) of a day-night schedule, and the effect of caffeine (300 mg) was studied during the overnight periods of work. The sleep electroencephalogram was recorded together with oral temperature and urinary electrolyte excretion. Impairment of performance within 9 h after the beginning of the daytime work period was minimal, and was limited to a test of continuous performance, but impairment of performance within 9 h after the beginning of the overnight work period was more pronounced and included lowered vigilance. Impaired performance overnight was related to time on task and circadian rhythmicity, and was alleviated to some extent by the use of caffeine.

Adult↗

PubMed1985

Histaminergic systems and sleep. Studies in man with H1 and H2 antagonists.

Effects of H1 (mepyramine, mequitazine, triprolidine and brompheniramine) and H2 (cimetidine and ranitidine) antagonists on sleep were studied in healthy man. There were no effects of mepyramine (50 and 100 mg), and the only effect of mequitazine (5 and 10 mg) was a reduction in the number of awakenings. Triprolidine (10 and 20 mg) and brompheniramine (4 and 8 mg) did not alter wakefulness during sleep or the total sleep time, but rapid eye movement sleep was reduced. There were no effects of ranitidine (150 and 300 mg), but slow wave sleep was increased by cimetidine (200 and 400 mg). It is tentatively suggested that the histaminergic system is concerned with the mechanisms which favour vigilance during the wakeful state, and the balance between wakefulness and slow wave activity during sleep. Effects of some H1 antihistamines on rapid eye movement sleep are believed to be due to their monoaminergic rather than their histaminergic activity.

Adolescent↗

PubMed1985

Central effects during the continuous osmotic infusion of a benzodiazepine (triazolam).

The effects of relatively constant plasma levels of a rapidly eliminated benzodiazepine (triazolam) were studied in young healthy males to determine whether tolerance to certain effects may develop over a relatively short period of time. The drug was given over a period of 30 h (2 days and 1 night) at zero-order rate using a rectal osmotic pump. Performance was measured at 2 hourly intervals during the day and was continuously impaired during the infusion, though there was a rapid recovery when the infusion ceased. All tasks were affected, in particular mental arithmetic and letter cancellation, but there was some improvement in performance during the second day. The normal circadian improvement in performance may have contributed to this effect, but some degree of tolerance to the effect of the drug cannot be excluded. Overnight there was a marked reduction in wakefulness, suppression of slow wave sleep, and delay to the onset and reduction in the duration of rapid eye movement sleep. During the night after infusion there was less slow wave sleep and increased wakefulness. The experimental design may prove useful in the study of tolerance to drugs.

Adult↗

PubMed1985

Studies on the possible central and peripheral effects in man of a cholinesterase inhibitor (pyridostigmine).

The effect of a reversible cholinesterase inhibitor (pyridostigmine: 30 mg, 8-hourly for 3 days) on psychomotor performance and visual function and on the electrical activity of the brain was studied in healthy man. It was not possible to detect any change during the six individual experimental sessions over the 3 days, but with pooling of the data there was a drug effect. The threshold for detection of a flickering light was increased and less responses were missed on a dynamic visual-acuity task. Visuo-motor coordination was impaired. The observations were consistent with the known activity of the drug and suggest an increase in central arousal and minimal alteration in motor coordination.

Adult↗