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Biomedical subjects

A N Nicholson

Publications and source records attributed to A N Nicholson.

At least 37 records · Page 2Linked to original sources
PubMed1990

Central effects of the angiotensin-converting enzyme inhibitor, captopril. II. Electroencephalogram and body sway.

1. Effects of single doses of captopril (12.5, 25 and 50 mg) on the electroencephalogram (EEG) and on body sway were studied in fourteen healthy male subjects. Oxazepam (15 mg), as an active control, and two placebos were included in the study, together with a single dose of atenolol (100 mg). Medication was administered double-blind at 11.00 h, and assessments made before and at 2 and 4 h after drug ingestion. 2. There were no changes in the EEG with captopril. Oxazepam reduced the circadian rise in alpha activity, while atenolol decreased beta power. Delta activity was modified by both oxazepam and atenolol. 3. A reduction in lower frequencies of body sway (0.05-1 Hz) occurred with captopril, while the spectra were unaffected by oxazepam. Atenolol increased (P less than 0.05) activity in the frequency range 0.75-2.75 Hz. 4. These observations suggest that captopril is free of central effects such as sedation that may occur with beta-adrenoceptor antagonists. Reduced body sway with captopril could reflect improved integration of central and peripheral control of posture.

Atenolol↗
PubMed1989

Modulation of sleep by trimipramine in man.

We have studied the acute effect of trimipramine (25, 50 and 75 mg) on nocturnal sleep in 6 young men. Fluoxetine (60 mg) and diazepam (10 mg) were included as controls for the potential changes in sleep measures. Trimipramine reduced awake activity, Stage 1 (drowsy) sleep, and the duration of rapid eye movement (REM) sleep. Non-REM (Stage 2) sleep was increased. Residual effects of trimipramine were present the next morning (9 h after ingestion) with impaired coding ability. The effects of trimipramine on sleep and daytime alertness are consistent with its complex pharmacological profile. Reduced wakefulness and sedation are most likely due to synergism between histamine H1, alpha 1-adrenoceptor, and dopamine receptor antagonism. Anticholinergic activity and possibly blockade of alpha 1-adrenoceptors would disturb the balance of transmitter activities which facilitates the optimal appearance of REM sleep. In this way the effects of trimipramine on nocturnal wakefulness and REM sleep are similar to drugs which inhibit the uptake of noradrenaline.

Adult↗
PubMed1989

Modulation of rapid eye movement sleep in humans by drugs that modify monoaminergic and purinergic transmission.

Modulation of rapid eye movement (REM) sleep is a well-established effect of many centrally acting drugs. However, there is uncertainty concerning the nature of the changes and their significance, and it is in this context that we have analyzed the effects of several groups of drugs that alter monoaminergic or purinergic transmission on sleep in humans. The analysis shows that drugs that modulate noradrenergic and serotonergic transmission lead to marked suppression of REM sleep, irrespective of any increase or decrease in sleep duration. There is no evidence that the timing of the ultradian cycle of REM sleep relative to sleep onset is altered by these drugs. On the other hand, reduced REM sleep with dopamimetic drugs is due solely to increased wakefulness. However, there can be more subtle effects of some drugs on REM sleep. Benzodiazepine receptor agonists and drugs that modify purinergic transmission modulate the appearance of early REM activity. There may, therefore, be two discrete systems that control entry into REM sleep, and that are responsive to drugs. The exact appearance and timing of REM periods may be modulated by a feedback mechanism involving GABAergic, or possibly purinergic, transmission, while monoaminergic and cholinergic influences exert a reciprocal and overriding control of REM sleep.

Anti-Anxiety Agents↗
PubMed1989

The influence of a 1 h nap on performance overnight.

The effect on performance overnight of a 1 h nap taken at 0200 h was studied in six young female subjects. The subjects completed three schedules, including one with a nap and two without a nap, during which either a placebo or 300 mg caffeine was ingested at 2315 h. Performance was measured from 1700 h in the evening until 1030 h the next morning. Caffeine improved performance overnight on almost all tasks compared with placebo. The nap had some limited beneficial effect compared with placebo, but most tasks remained impaired.

Adult↗
PubMed1989

Rapid eye movement sleep and sleep continuity. Depression and antidepressants.

Abnormalities of sleep and mood occur in depressive illness, and both disturbances may respond to therapy. Antidepressant drugs of all classes bring about immediate and often pronounced changes in sleep. Some drugs reduce, whereas others increase, nocturnal wakefulness, but most, if not all, suppress rapid eye movement activity, although it is uncertain whether this is linked directly to elevation of mood. Such changes in sleep continuity are related to the individual pharmacological profile of drugs, and in some instances, such as with trimipramine, may arise from the interaction of properties which alone may not lead to marked effects on sleep. On the other hand, inhibition of REM sleep appears to be related to a nonspecific disturbance of the balance between monoaminergic and cholinergic influences. In this way, REM sleep is reduced not only with drugs which selectively modulate noradrenaline or serotonin activity, but also with drugs which have complex pharmacological profiles.

Antidepressive Agents↗
PubMed1988

Studies on the modulation of the sleep-wakefulness continuum in man by fluoxetine, a 5-HT uptake inhibitor.

The effects of an inhibitor of the uptake of 5-hydroxytryptamine (5-HT) fluoxetine (20, 40 and 60 mg), on nocturnal sleep and on alertness during the day, were studied in healthy adults. Fluoxetine reduced the total sleep time and the duration of rapid eye movement (REM) sleep and increased awake activity and stage 1 (drowsy) sleep during the night. Daytime sleep latencies were longer after fluoxetine but, paradoxically, the subjects felt more drowsy and coding ability was impaired. It is considered that the alerting effect of fluoxetine in man is most likely related to modulation of 5-HT-mediated transmission, whereas suppression of REM sleep is a nonspecific effect which arises when the balance of monoaminergic and cholinergic influences is disturbed. It is suggested that the serotonergic system has a pervasive influence throughout the sleep-wakefulness continuum, in contrast with some other neurotransmitter systems, which may be more concerned with the subtle manifestations of vigilance.

Adult↗
PubMed1988

Altitude insomnia: studies during an expedition to the Himalayas.

During an expedition to the Himalayas, we studied the sleep and respiration of six climbers. Three ingested acetazolamide (500 mg) daily throughout the climb and the other three ingested placebo. At high altitude (4,150-4,846 m), each subject ingested temazepam (10 mg) for one night and placebo for another. Acetazolamide improved sleep above 2,750 m, but it is uncertain whether this was due to sedation or to improvements in arterial oxygen saturation. Sleep was markedly disturbed in all subjects above 4,000 m. Temazepam improved sleep, and in subjects taking acetazolamide, it reduced sleep-onset latencies and increased sleep efficiency close to that of sea level values. These observations suggest that the prophylactic use of acetazolamide is likely to improve sleep in climbers and that a low dose of a benzodiazepine such as temazepam (10 mg) may be beneficial at high altitude. Studies are now needed to exclude any possibility of respiratory impairment at altitude before a firm recommendation can be made regarding the routine use of this hypnotic.

Acetazolamide↗
PubMed1988

Central effects of beta-adrenoceptor antagonists. I--Performance and subjective assessments of mood.

1. Central effects of the beta-adrenoceptor antagonists, propranolol (40, 80 and 160 mg) and atenolol (50 and 100 mg) were studied in 12 healthy male subjects. Two placebo ingestions and an active control (oxazepam 15 mg) were included. Single doses were administered double-blind at 11.00 h, and assessments of performance and subjective feelings were made before, 2 h and 4 h after ingestion. 2. Performance was measured using letter cancellation, digit symbol substitution, continuous attention, choice reaction time, finger tapping, short term and immediate memory, critical flicker fusion and two flash fusion. Subjective feelings were assessed using twelve visual-analogue scales. 3. Oxazepam impaired performance at letter cancellation (P less than 0.001), digit symbol substitution (P less than 0.05), continuous attention (P less than 0.001), immediate recall (P less than 0.05) and finger tapping (P less than 0.05), but neither of the beta-adrenoceptor antagonists affected these measures. Propranolol (40 and 160 mg) also impaired short term memory (P less than 0.05), though it was not possible to establish this effect with atenolol. 4. Subjective alertness was reduced by oxazepam (P less than 0.01) and atenolol (P less than 0.05), while propranolol (40 mg) reduced anxiety (P less than 0.01) and propranolol (80 mg) impaired ability to concentrate (P less than 0.05). 5. The results suggest that both lipophilic and hydrophilic antagonists modify the central nervous system, though impairment may be difficult to establish with conventional tests. The observations on memory and alertness suggest that the central effect of beta-adrenoceptor antagonists may be subtle.

Adrenergic beta-Antagonists↗
PubMed1988

Central effects of beta-adrenoceptor antagonists. II--Electroencephalogram and body sway.

1. Effects of the beta-adrenoceptor antagonists, propranolol (40, 80 and 160 mg) and atenolol (50 and 100 mg) on the electroencephalogram and on body sway, were studied in 12 healthy male subjects. The study was double-blind, and included two placebos and an active control, oxazepam (15 mg). Medication was ingested at 11.00 h, and assessments were made before, and at 2 h and 4 h after ingestion. 2. All doses of both beta-adrenoceptor antagonists modified the electroencephalogram, and the changes reported were statistically significant at probability levels of less than 5%. The circadian rise in alpha activity was reduced by both beta-adrenoceptor antagonists as well as by oxazepam. Atenolol also decreased beta activity. 3. Body sway was modified by atenolol and oxazepam (P less than 0.05). The increase with oxazepam was most marked in the low frequency component (0.05-2.25 Hz) of the spectrum, while atenolol modified only the component of higher frequency (2.25-4.0 Hz). 4. These observations suggest that propranolol and atenolol have a sedative effect, and that hydrophilic antagonists are unlikely to be free of central activity. The changes in body sway could imply that peripheral mechanisms may be modified at least with atenolol.

Adrenergic beta-Antagonists↗
PubMed1987

Studies on performance with aspirin and paracetamol and with the centrally acting analgesics meptazinol and pentazocine.

Effects of aspirin (325 and 650 mg) and paracetamol (500 and 1000 mg), and of the centrally acting analgesics meptazinol (100 and 200 mg) and pentazocine (25 and 50 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 seven healthy female adults. The study was double-blind and placebo controlled, and triprolidine (10 mg) was used as the active control. No effects of meptazinol and paracetamol on performance were observed. Pentazocine (25 mg) impaired performance on digit symbol substitution (p less than 0.05) and aspirin (650 mg) appeared to have shortened complex reaction time (p less than 0.05). Meptazinol (100 mg) increased the component of mood assessments related to wakefulness (p less than 0.05). Impaired performance with pentazocine may involve opioid receptor activity, while the apparent alerting effect of meptazinol may relate to its cholinergic activity. The possible effect of aspirin on reaction time needs to be confirmed.

Acetaminophen↗
PubMed1987

Studies on the central effects of the H1-antagonist, loratadine.

Effects of loratadine (10, 20 and 40 mg) on visuo-motor coordination, dynamic visual acuity, short-term memory, digit symbol substitution, and on subjective assessments of mood were tested before, and 0.5, 1.5, 3.5 and 5.5 h after ingestion by 6 healthy female adults. There were no effects of 10 or 20 mg loratadine. With 40 mg loratadine the number of substitutions on the digit symbol test was reduced 5.5 h after ingestion, and on dynamic visual acuity response time was increased at 3.5 h and the number of responses missed was increased at 5.5 h. Triprolidine (10 mg) which was used as active control impaired performance on all the tasks and impaired performance was observed at all times after ingestion. Loratadine is a promising antihistamine for individuals involved in skilled activity. The anticipated single daily dose of 10 mg is unlikely to impair performance.

Adult↗
PubMed1987

Rapid eye movement sleep in man: modulation by benzodiazepines.

The modulation of rapid eye movement REM sleep in man by benzodiazepines has been analysed using 366 sleep recordings with at least 3 REM periods, obtained in 25 individuals, over 9 years. Sleep-dependent and sleep-independent mechanisms are believed to control REM activity, and the effect of benzodiazepines can be explained if the sleep-dependent influence is modified. It is suggested that a negative feedback mechanism, which usually encourages the appearance of REM periods, is depressed, while a threshold and oscillator which determine the cyclical appearance of the activity, and its relation with the onset of sleep, are unaffected.

Adult↗
PubMed1987

Efficacy of zopiclone in middle age.

Effects of zopiclone (5.0, 7.5, and 10 mg) on sleep and on performance were studied in middle-aged subjects. Zopiclone (5.0-10.0 mg) reduced awake activity and the number of awakenings, and increased the duration of stage 2 sleep. The appearance of REM sleep was delayed, but this effect was without reduction over the whole night. There were no impairments in the digit symbol substitution test when zopiclone was compared with placebo, although there were less substitutions with 10.0 mg than with 5.0 mg. Symbol copying and choice reaction time were unaltered. Zopiclone would appear to be a useful hypnotic for those involved in skilled work. Based on the results obtained in healthy volunteers, the 5.0 mg dose would be appropriate for many; if in insomniac patients, 7.5 mg was needed, then it is likely to be free of undue impairment of performance the next day.

Azabicyclo Compounds↗
PubMed1987

1986 Stewart memorial lecture. Sleep and wakefulness of the airline pilot.

There are two overriding concerns in the design of schedules for aircrew who have to cope with irregularity of their sleep due either to work at unusual times of the day or to time zone changes. The first is that aircrew must be able to achieve an acceptable sleep pattern, and this is likely to involve short periods of sleep and naps. These, in turn, depend on limits to duty hours. The second is that the arrangement of work must bear in mind that prolonged duty and duty at certain times of the day may both involve relatively low levels of performance, and modelling can identify the adverse interactions of these influences. It is also important that the quality of the sleep of the individual pilot is taken into consideration when there are undue difficulties in coping with irregularity of work.

Adult↗
PubMed1986

Sleep after transmeridian flights.

Nocturnal sleep and daytime sleep latencies, recorded electroencephalographically after westward and eastward flights across the North Atlantic involving time zone shifts of 5 h, were influenced by the time of the flight and by subsequent displacement of the rest period. After the westward flight there was sleep disturbance during the latter part of the first night. However, there was persistent disturbance of sleep after the eastward flight. A rapidly eliminated hypnotic may be useful for the first night or two after a westward flight and for a few nights after an overnight eastward flight.

Adult↗