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Biomedical subjects

A N Nicholson

Publications and source records attributed to A N Nicholson.

At least 73 records · Page 4Linked to original sources
PubMed1985

Central effects of H1 and H2 antihistamines.

H1-antihistamines are usually associated with impairment of central nervous functions, but unacceptable decrements in performance may not be an inevitable sequel of their use. Effects are dependent on the ability of a particular drug to cross the blood brain barrier, and so compounds which cross so slowly that tolerance of the central nervous system can develop gradually without any immediate changes in performance are of interest. However, sustained release formulations and compounds which have a selective affinity for the peripheral receptor may also have their part to play in the management of allergic states in those involved in skilled activity. As far as H2-antagonists are concerned, it is likely that as they are less liposoluble they would be free of central effects. Studies on the central effects of H1 and H2 antagonists are reviewed, and tentative recommendations are made in respect of these findings concerning the possible use of these drugs in aircrew.

Aerospace Medicine↗
PubMed1985

Sustained performance with short evening and morning sleeps.

The effect which early evening sleep may have on overnight and subsequent daytime performance, and the effect which morning sleep may have on daytime performance after overnight sleep deprivation has been studied in six healthy male volunteers. It would appear that relatively short periods of natural and drug induced (brotizolam 0.125 mg) sleep have a beneficial effect on subsequent performance even in the absence of preceding sleep debt. In the event of disturbed sleep in shiftwork an hypnotic may be helpful, and in this context, one which is rapidly eliminated and sustains sleep is appropriate.

Adult↗
PubMed1985

Hypnotics and aircrew.

The management of sleep difficulties which arise during air operations must be related, at least initially, to the cause, but the aeromedical specialist is frequently faced with the possible use of hypnotics. There are no simple guidelines, but an understanding of various issues will help toward the effective use of these drugs in those who have to cope with irregularity of rest and carry out skilled work. Some knowledge of the pharmacokinetics of the drugs concerned is useful as persistence of effect and the potential for accumulation with repeated ingestion are important factors, while efficacy in relation to sleep of different durations and at unusual times must also be considered.

Adult↗
PubMed1984

Flurazepam hydrochloride and its principal metabolites: behavioural studies in the monkey (Macaca mulatta).

Effects of flurazepam and its two principal metabolites, hydroxyethylflurazepam and desalkylflurazepam (0.5, 1.0, 3.0 and 10.0 mg/kg), were studied on a delayed differentiation task in the monkey. Flurazepam (10.0 mg/kg) and hydroxyethylflurazepam (3.0 and 10.0 mg/kg) decreased the number of correct responses and increased response latency; effects persisted to 4 h with the highest dose. Marked impairment of performance was observed with all doses of desalkylflurazepam and effects of 3.0 and 10.0 mg/kg persisted to 24 h. Evidence of a disinhibitory effect of desalkylflurazepam was demonstrated. The study would point to a consideration of both metabolites in the hypnotic effect and in the impairment of performance observed after acute ingestion of flurazepam in man.

Animals↗
PubMed1984

The H2-antagonists, cimetidine and ranitidine: studies on performance.

The effects of single oral doses of cimetidine (200 and 400 mg) and ranitidine (150 and 300 mg) were evaluated on visuo-motor coordination, dynamic visual acuity, digit symbol substitution, symbol copying, and critical flicker fusion, and on subjective assessments of mood and well-being in seven healthy female volunteers. The study was double blind and placebo controlled, and triprolidine (10 mg) was used as an active control. With cimetidine and ranitidine there were no adverse changes in performance, central nervous function or subjective assessment of mood. Triprolidine impaired visuo-motor coordination, reduced the number of substitutions on the digit symbol substitution test and the number of symbols copied, lowered the critical flicker fusion threshold and reduced dynamic visual acuity. Cimetidine (200-400 mg) and ranitidine (150-300 mg) are highly unlikely to impair performance, and may be used in individuals involved in skilled activity.

Adult↗
PubMed1984

Studies on the possible central effects in man of a neuropeptide (ACTH 4-9 analogue).

The central effects of a neuropeptide, ACTH 4-9 analogue (Organon 2766), were studied in man using digit symbol substitution (DSS), symbol copying, digit span, electroencephalography and auditory evoked potentials, critical flicker fusion (CFF) and pupillary response to light. Performance was measured overnight, and each of 6 subjects ingested 300 mg caffeine, 40 mg ACTH 4-9 analogue and matching placebo. With placebo there was a marked deterioration in performance overnight. The number of substitutions on DSS and the numbers of symbols copied fell, and the threshold for CFF and number of errors on the vigilance task increased. These effects were not seen after ingestion of caffeine (300 mg), though caffeine may have led to some deterioration in the ability to remember digits. The neuropeptide did not attenuate the decrements in performance overnight.

Adrenocorticotropic Hormone↗
PubMed1984

Activity of the chloro- and triazolo-benzodiazepines. Behavioural studies in the monkey (Macaca mulatta).

The effects of 1,4-benzodiazepines with various heterocyclic ring structures (triazolo, triazino and imidazo), and of 1,4-benzodiazepines with chlorine substitution in the phenyl ring (4'- chlorodiazepam , 2'- chlorodiazepam and 2'- chloronordiazepam ) were studied on spatial-delayed alternation and delayed matching-to-sample tasks in the monkey. Within the dose range 0.25-0.75 mg kg-1, the triazolo compounds had marked activity, decreasing the number of correct responses and increasing total response time. The triazino was less potent and the imidazo compounds were the least likely to disrupt performance. Smaller doses (0.005, 0.01 and 0.05 mg kg-1) of triazolam did not impair performance on the tasks, and larger doses of imidazo (1.0, 3.0 and 7.5 mg kg-1) were without effect on delayed alternation. Within the dose range 1.0-10.0 mg kg-1, 4'- chlorodiazepam was without effect and only the largest dose of diazepam and 2'- chlorodiazepam impaired performance. 2'- Chloronordiazepam decreased the number of correct responses at all doses (1.0, 3.0 and 10.0 mg kg-1) and with the largest dose, the total response time was increased. The studies suggest that the effects of a drug on higher nervous function in the monkey cannot easily be predicted from standard pharmacological tests in other animals or other species of monkey.

Animals↗
PubMed1984

Visual motor co-ordination and dynamic visual acuity.

Data on the effect of an antihistamine (triprolidine 10 mg) on visuo-motor coordination and dynamic visual acuity were used to establish interactions between these skills. Analysis of covariance and principal component analysis were used. The analyses suggested two main effects--an effect on the activity of the neuromuscular system and one which impaired ability to anticipate target movement. Detection of impaired performance by any task may have wider implications to the effectiveness of the individual than that obviously suggested by the skill itself.

Humans↗
PubMed1984

Pharmacodynamic correlates of modified absorption: studies with lormetazepam.

The bioavailability, pharmacokinetics, and effects on performance of lormetazepam (1 mg) have been compared using soft gelatin capsule and tablet formulations. Lormetazepam was more rapidly absorbed from the soft gelatin capsule (tmax = 1.0 +/- 0.2 h) than from the tablet (tmax = 2.4 +/- 0.4 h), and the plasma concentration-time curve for the capsule was shifted to the left. Bioavailability and elimination kinetics did not differ between the formulations. The number of substitutions in the digit symbol test was reduced between 0.5 and 1.5 h for both formulations (P less than 0.001), but the degree of impairment at 0.5 h was greater after the capsule than after the tablet (P less than 0.01). Visuo-motor co-ordination was impaired from 0.5 to 1.5 h after the tablet and the capsule (P less than 0.01), and extended to 5.5 h after the tablet (P less than 0.05). These observations reflect the differences in the plasma concentration-time curves.

Absorption↗
PubMed1984

Sleep of shiftworkers within the arctic circle.

The sleep of shiftworkers in the Arctic has been investigated using electroencephalography. The subjects were studied four times a year over a 2-year period. There was a trend toward less restful sleep during the autumn and winter months, but otherwise sleep at various times of the day was similar to that of individuals elsewhere. This would suggest that sleep disturbance in polar shiftworkers can be managed in a similar way to that of shiftworkers in temperate regions.

Adult↗
PubMed1984

Adaptation to irregularity of rest and activity.

The adaptation to a 9-d schedule of irregular rest and activity was studied. Sleep was recorded; patterns of oral temperature, urinary excretion, and performance at a series of tasks were measured. The relationships between circadian rhythmicity, length of time on task, and cumulative sleep loss were examined.

Activity Cycles↗
PubMed1984

Biological studies with continuous-wave radiofrequency (28 MHz) radiation.

Effects of high-frequency (28 MHz) continuous-wave radiation have been studied in the rat and monkey. No histopathological (rat-125 mW cm-2 for 28 days) or hematological (monkey-25 mW cm-2 for 24 days) changes could be attributed to the radiation. In the monkey (125 mW cm-2 for 11 days) there was an increase in urinary calcium concentration which was most likely due to restricted movement. In the rat (220 mW cm-2 for 13 days) there was reduced uptake of iodine by the thyroid, lower levels of plasma thyroid-stimulating hormone, and reduced ratio of protein bound to nonprotein bound iodine. Food consumption was also decreased. The changes are likely to have arisen as a compensatory response to an induced heat load. A nonthermal effect of continuous-wave high-frequency radiation has not been shown in this study. The effects were likely to be associated with either physiological compensation for induced heating or restriction of movement.

Animals↗
PubMed1983

Antihistamines and sedation.

With careful use of antihistamines central effects may be minimised or even largely avoided while adequate peripheral antihistaminic activity is preserved. Tolerance to central effects may develop quickly with some drugs, so that sedation is no longer troublesome after a few days. With sustained-release antihistamines, early-evening dosage may provide sufficient activity, without sedation, the next day. For patients in whom daytime sedation is troublesome three drugs, astemizole, mequitazine, and terfenadine, are likely to prove useful. However, the response of the individual patient cannot be predicted, and the possibility of sedation can never be completely excluded.

Astemizole↗
PubMed1983

The H1-antagonist mequitazine: studies on performance and visual function.

The effects of single oral doses of mequitazine (5 and 10 mg), terfenadine (60 mg) and triprolidine (10 mg) as active controls, and placebo were evaluated on visuo-motor coordination, digit symbol substitution, critical flicker fusion and dynamic visual acuity, and on subjective assessments of mood and well-being in six normal female volunteers. The study was double-blind. Mequitazine (5 mg) impaired visuo-motor coordination 7.5 h after ingestion (considered to be a chance result), but there was no effect on digit symbol substitution, critical flicker fusion threshold or dynamic visual acuity. Mequitazine (10 mg) impaired visuo-motor coordination and reduced the number of substitutions on the digit symbol substitution test. Terfenadine (60 mg) had no effect on performance or on subjective feelings. Triprolidine (10 mg) impaired visuo-motor coordination, reduced the number of substitutions on the digit symbol test, lowered the critical flicker fusion threshold and reduced dynamic visual acuity. Mequitazine (5 mg) and terfenadine (60 mg) are likely to prove acceptable H1 antagonists when sedation must be avoided.

Adult↗
PubMed1983

Variability of response to hypnotics: sleep studies in man.

Effect of diazepam on sleep in man was investigated in a series of placebo controlled studies and the data on various measures from two groups (young adults and middle age) were retrospectively analysed. Variability of the measures between the two groups with placebo was not different, but the variability of their response to the drug was different, and that of the middle aged group was high. In the young adults there were drug effects, but in the middle aged group no drug effects could be established. The studies suggest that variability of data must be taken into consideration when it is used to indicate the most appropriate dose range. If the variability of response is low the data may indicate the likely effect of the drug on each individual. On the other hand if the variability is high then data obtained from analysis of the group may have limited relevance, and suggest doses which are too high for the majority of the individuals within that group.

Adolescent↗