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Biomedical subjects

J F O'Hanlon

Publications and source records attributed to J F O'Hanlon.

At least 19 recordsLinked to original sources
PubMed1998

Fexofenadine's effects, alone and with alcohol, on actual driving and psychomotor performance.

BACKGROUND: Fexofenadine is the hydrochloride salt of terfenadine's active metabolite. OBJECTIVE: Fexofenadine's effects on performance were assessed in this study for the purpose of determining its safety of use by patients who engage in potentially dangerous activities, especially car driving. METHODS: Fexofenadine was administered in daily doses of 120 or 240 mg, each in single and divided units given over 5 days. Two milligrams of clemastine given twice daily and placebo were given in similar series. Twenty-four healthy volunteers (12 men, 12 women; age range, 21 to 45 years) participated in a double-blind six-way crossover study. Psychomotor tests (critical tracking, choice reaction time, and sustained attention) and a standardized actual driving test were undertaken between 1.5 to 4 hours after administration of the morning dose on days 1, 4, and 5 of each series. On day 5, subjects were challenged with a moderate alcohol dose before testing. RESULTS: Fexofenadine did not impair driving performance. On the contrary, driving performance was consistently better during twice daily treatment with 120 mg fexofenadine than during treatment with placebo, significantly so on day 4. Both of the 240 mg/day regimens significantly attenuated alcohol's adverse effect on driving on day 5. Effects in psychomotor tests were not significant, with the exception of the critical tracking test in which the first single doses of fexofenadine, 120 and 240 mg, had significantly impairing effects. CONCLUSION: It was concluded that fexofenadine has no effect on performance after being taken in the recommended dosage of 60 mg twice daily.

Adult↗
PubMed1998

Venlafaxine's effects on healthy volunteers' driving, psychomotor, and vigilance performance during 15-day fixed and incremental dosing regimens.

Effects of venlafaxine, an antidepressant acting by selective serotonin and norepinephrine reuptake inhibition with a potency ratio of 5:1, were assessed in a standardized, actual driving test, a battery of psychomotor tests (Critical Flicker/Fusion Frequency, Critical Tracking, Divided Attention), and a 45-minute vigilance test (Mackworth Clock). Thirty-seven healthy volunteers, 22 of whom completed the study, received venlafaxine in fixed (37.5 mg twice a day) and incremental (37.5-75 mg twice a day) doses as well as mianserin (10-20 mg three times a day) and placebo according to a 4-period (15 days each), double-blind, crossover design. Testing occurred on days 1 and 7 and after dose increments, on days 8 and 15. Plasma concentrations of venlafaxine and its active metabolite were measured on test days for confirming compliance. Venlafaxine had no significant effect on the primary driving parameter (standard deviation of lateral position) and failed to impair psychomotor performance. Mianserin profoundly and consistently impaired driving and psychomotor performance. However, both drugs significantly impaired vigilance performance. Maximal effects occurred on day 1 with mianserin and similarly on day 7 with venlafaxine in both series. The increment in venlafaxine's dose on day 8 did not increase this effect. The drug's selectively impairing effect on vigilance is shared by other "serotonergic" anxiolytics and antidepressants, suggesting that interference with 5-HT transmission reduces arousal in particularly monotonous tasks or environments. This study concludes that venlafaxine does not generally affect driving ability and should be safe for use by patients who drive.

Adult↗
PubMed1997

Considering the P450 cytochrome system as determining combined effects of antidepressants and benzodiazepines on actual driving performance of depressed outpatients.

Parallel groups of depressed (DSM III-R) outpatients received moclobemide (n = 22) and fluoxetine (n = 19), double blind, for 6 weeks. Respective starting doses were 150 mg twice a day and 20 mg q.a.m. These could be doubled after 3 weeks for greater efficacy. Chronic users of benzodiazepine anxiolytics continued taking them as comedication. Therapeutic and side effects were assessed using conventional rating scales. Actual driving performance was assessed during the week before therapy and at 1, 3 and 6 weeks thereafter using a standardized test that measures standard deviation of lateral position (SDLP). Similar remissions in depressive symptoms and side effects occurred in both groups. Patients drove with normal and reliable (r = 0.87) SDLPs before treatments. Most continued to do so but a few drove with progressively rising SDLPs and the overall trends were significant in both groups (p < 0.03). A post-hoc multiple regression analysis was applied for identifying factors that correlated with SDLP in separate tests after the beginning of therapy. At 3 and 6 weeks there were significant (p < 0.03) relationships involving the same factor; patients who drove with progressively higher SDLPs appeared to be those using benzodiazepines that are metabolized by a P450 isozyme subject to inhibition by their particular antidepressant.

Adolescent↗
PubMed1996

Effects of mefloquine alone and with alcohol on psychomotor and driving performance.

OBJECTIVE: To determine whether mefloquine, a quinoline antimalarial drug, affects psychomotor and actual driving performance when given in prophylactic regimen, alone or in combination with alcohol. METHODS: Forty male and female volunteers were randomly assigned in equal numbers to two groups, and were treated double-blind for one month with mefloquine and placebo. The medication was taken in a 250 mg dose on the evenings of Days 1, 2, 3, 8, 15, 22 and 29. Testing was done on Days 4, 23 and 30, the latter after repeated doses of alcohol sufficient to sustain a blood concentration of about 0.35 mg.ml-1. Two real driving tests were used to measure prolonged (1 h) road tracking and car following performance. Critical Flicker/Fusion Frequency (CFF), critical instability tracking and body sway were also measured in the laboratory. RESULTS: Mefloquine caused no significant impairment in any test at any time relative to placebo. It significantly improved road tracking performance on Day 4. A significant interaction between prior treatment and alcohol was found in the body sway test, as the alcohol-induced change was less after mefloquine than placebo. The sensitivity of the driving test and the CFF test were shown by the significant overall effect of alcohol which did not discriminate between the two prior treatments. CONCLUSION: Mefloquine did not impair driving performance but rather improved it in the longer test, suggesting that the drug may possess psychostimulating properties.

Adult↗
PubMed1996

Effects of semprex-D and diphenhydramine on learning in young adults with seasonal allergic rhinitis.

OBJECTIVES: The purpose of this study was to test the hypothesis that learning ability is impaired in patients with seasonal allergic rhinitis relative to untreated individuals and to evaluate a combination compound (acrivastine 8 mg + pseudoephedrine 60 mg) for attenuation of the learning impairment in these patients. BACKGROUND: In a previous study employing the same method it was shown that young children (10 to 12 yrs) suffering from seasonal allergic rhinitis performed significantly worse on tests of learning and using knowledge after acute treatment with a sedating antihistamine (diphenhydramine 50 mg) or placebo as compared with nontreated healthy controls. This effect was partially reversed by treatment with loratadine. METHODS: Sixty-seven young adults suffering from seasonal allergic rhinitis and 28 matched controls were trained on didactic simulation for three consecutive days. Atopic subjects were treated differentially during training according to a double-blind, randomized, parallel group design with either diphenhydramine hydrochloride 50 mg, a combination compound (acrivastine 8 mg + pseudoephedrine 60 mg, A + P), or placebo, administered qd. After training, all atopic subjects were maintained on A + P treatment for 14 days at which time all groups returned for examination. RESULTS: Mean performance at the end of training was worse for all atopic subjects combined compared with normal subjects. Subjects treated with diphenhydramine performed significantly worse than either normals (P < .001) or those treated with A + P (P < .001). At the examination, the diphenhydramine group's performance differed significantly from those of the normal (P < .001) and A + P groups (P < .001). CONCLUSION: The study supports our previous finding that allergy symptoms reduce learning ability which is further reduced learning ability which is further reduced by diphenhydramine. Atopic subjects with allergies treated with acrivastine + pseudoephedrine learned as well as normal subjects.

Adolescent↗
PubMed1995

Comparison of acute alprazolam (0.25, 0.50 and 1.0 mg) effects versus those of lorazepam 2 mg and placebo on memory in healthy volunteers using laboratory and telephone tests.

This study was designed to confirm the hypothetical dose-dependent effect of alprazolam on memory and to compare its effects on tests measuring different aspects of cognitive and psychomotor functioning. A secondary purpose was to compare the sensitivity of newly developed telephone tests with a standard laboratory test of memory. Twenty healthy male volunteers (aged 18-35 years) participated in a five-way double-blind crossover design. Treatments were single oral doses of alprazolam (0.25, 0.5 and 1.0 mg), placebo and lorazepam 2.0 mg. The latter was included as an internal control for demonstrating sensitivity of the method. Lorazepam significantly impaired all performance measures except two: verbal fluency and accuracy of music recognition were insensitive to drug effects. Alprazolam had clear dose-dependent effects on different aspects of memory: 0.25 mg did not affect any parameter; 0.5 mg impaired performance in a Word Learning Test and a Spatial Memory Test and also psychomotor performance; 1.0 mg additionally impaired Syntactic Reasoning, Semantic Verification, and Critical Flicker Fusion performance. Alprazolam's effects were not selective for any of the cognitive functions as measured in this study. The telephone tests were clearly less sensitive than the standard test, though sufficient for showing significant effects of alprazolam 1 mg and lorazepam 2 mg.

Adolescent↗
PubMed1995

Acute and subchronic effects of paroxetine 20 and 40 mg on actual driving, psychomotor performance and subjective assessments in healthy volunteers.

The effects of paroxetine (20 and 40 mg/day) and amitriptyline (75 mg/day, used as an active control) on car driving and psychomotor function were compared with those of placebo in a double-blind, crossover study employing 16 healthy subjects. Performance testing occurred on the first and last day of each 8-day treatment series. Side-effects, sleep duration and sleep quality were rated daily. Amitriptyline produced severe drowsiness and strikingly impaired performance on nearly every test on the first day but its effects were practically gone after 1 week of treatment. Paroxetine 20 mg, the usual antidepressant dose, had no effect on performance. Paroxetine 40 mg did not affect road tracking but slightly impaired performance in some psychomotor tests in a persistent manner. Paroxetine had no effect on sleep following the 20 mg dose but reduced quality following the 40 mg dose. Side-effects that the administered drugs have in common were milder during paroxetine than amitriptyline treatment. However, some dose-related side-effects (e.g. nausea and delayed ejaculation) were only reported during paroxetine treatment.

Adult↗
PubMed1995

A comparative study of acute and subchronic effects of dothiepin, fluoxetine and placebo on psychomotor and actual driving performance.

1. The acute and subchronic effects of dothiepin 75-150 mg and fluoxetine 20 mg on critical fusion frequency (CFF), sustained attention and actual driving performance were compared with those of placebo in a double-blind, cross-over study involving 18 healthy volunteers. Drugs and placebo were administered for 22 days in evening doses. Fluoxetine doses were constant but dothiepin doses increased on the evening of day 8. Performance was assessed on days 1, 8 and 22 of each treatment series. Subjective sleep parameters and possible side effects were recorded on visual analogue scales on alternate treatment days. 2. Dothiepin reduced sustained attention on day 1 by 6.7% (95% confidence interval (C1): -12.0 to -1.3%) and CFF on day 22 by 1.1 (CI: -2.2 to -0.1) Hz. Fluoxetine reduced sustained attention days 1, 8 and 22 of treatment by 7.4, 6.7 and 6.5% respectively (CI: -11.3 to -3.6; -14.3 to -1.5 and -9.5 to -3.4). CFF decreased linearly over days during fluoxetine treatment and significantly differed from placebo on day 22 with 1.2 Hz (CI: -2.3 to -0.2). Neither drug significantly affected driving performance. Whilst receiving dothiepin, subjects complained of drowsiness on days 1-3 of treatment (mean rank 5.6; CI: 2.0 to 9.2) and slept 43 min longer (CI: 8.2 to 76.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Antihistamine effects on actual driving performance in a standard test: a summary of Dutch experience, 1989-94.

The review summarizes the major results of eight double-blind, placebo-controlled, volunteer studies undertaken by three independent institutions for showing the effects on actual driving performance of "sedating" and "nonsedating" antihistamines (respectively, triprolidine, diphenhydramine, clemastine and terfenadine, loratadine, cetirizine, acrivastine, mizolastine, and ebastine). A common, standardized test was used that measures driving impairment from vehicular "weaving" (i.e., standard deviation of lateral position (SDLP)). Logical relationships were found between impairment and dose, time after dosing, and repeated doses over 4-5 days. The newer drugs were generally less impairing, but differences existed among their effects, and none was unimpairing at doses 1-2x the currently recommended levels. One or possibly two of the newer drugs possessed both performance-enhancing and -impairing properties, depending on dose, suggesting two mechanisms of action.

Automobile Driving↗
PubMed1995

Anxiolytics' effects on the actual driving performance of patients and healthy volunteers in a standardized test. An integration of three studies.

Effects of benzodiazepine (diazepam, lorazepam) and benzodiazepine-like anxiolytics (alpidem, suriclone) and a 5-HT-3 antagonist (ondansetron) on actual driving performance were measured in three double-blind, placebo-controlled studies. Subjects were healthy volunteers in two and anxious patients in the third. Treatments lasted for 8 days. Standardized testing occurred within the first full day and on the last day of treatment. No important differences existed between volunteers' and patients' baseline and/or placebo performances and both groups responded similarly to comparable drugs/doses. Benzodiazepine and benzodiazepine-like anxiolytics produced marked and pervasive driving impairment, which lasted throughout treatment; but ondansetron, none.

Anti-Anxiety Agents↗
PubMed1994

Effects of mizolastine and clemastine on actual driving and psychomotor performance in healthy volunteers.

The acute effect of doses of mizolastine 5, 10, 20 and 40 mg, an active control (clemastine 2 mg) and placebo on actual car driving and psychomotor performance have been compared. Twenty four healthy volunteers were treated according to a double-blind, 6-way cross-over design. In the driving test, lasting about 1 h, lateral position control and speed were continuously measured; the psychomotor test battery, lasting 50 min, comprised critical flicker-fusion frequency, critical instability tracking, divided attention, memory search and choice reaction time, and vigilance studies; and mood changes and possible adverse-effects were rated on visual analogue scales. The results showed a dose-response relationship: mizolastine 40 and 20 mg impaired driving and psychomotor performance. The effect of mizolastine 40 mg on driving was strongly correlated with that of clemastine (r = 0.78) and was comparable to the effect of a blood ethanol level of 0.8 mg.ml-1. Mizolastine 5 mg and 10 mg did not have a significant effect on driving performance and psychomotor tests. It was concluded that at a 10 mg dose of mizolastine, the therapeutic dose, it could be considered a safe anti-histamine, although individual adverse reactions cannot be completely ruled out.

Adult↗
PubMed1994

Acrivastine, terfenadine and diphenhydramine effects on driving performance as a function of dose and time after dosing.

The study was conducted according to a nine-way, observer- and subject-blind, cross-over design. Its purpose was to compare the single-dose effects of the following drugs on driving performance: acrivastine (8, 16 and 24 mg); the combination of acrivastine (8 mg) with pseudoephedrine (60 mg); terfenadine (60, 120 and 180 mg); diphenhydramine-HCl (50 mg); and placebo. The subjects were 18 healthy female volunteers. Drug effects were assessed in two repetitions of two driving tests (highway driving and car-following) after each treatment. Acrivastine's impairing effects in both driving tests were similarly dose-related. The 8-mg dose had a small, but significant, effect on highway driving in the first trial. The 16-mg and 24-mg doses significantly impaired driving in both tests during the first trial and the 24-mg dose did so again during the second trial. Neither the combination of acrivastine with pseudoephedrine nor terfenadine caused any significant impairment of performance. Diphenhydramine significantly impaired driving in both tests during every trial. In conclusion, the normal therapeutic dose of acrivastine (8 mg) had little effect on driving performance, and virtually none when that dose was given in combination with pseudoephedrine (60 mg). Higher doses of acrivastine severely impaired driving performance. Terfenadine had no significant effect on driving performance after any dose while diphenhydramine strongly impaired every important driving parameter.

Administration, Oral↗
PubMed1994

A cross-study comparison of the effects of moclobemide and brofaromine on actual driving performance and estimated sleep.

Results from two separate studies were combined to compare the acute and subchronic effects of two monoamine oxidase-A (MAO-A) inhibitors, moclobemide and brofaromine, on actual driving performance and sleep. Both studies were conducted according to a double-blind, crossover design involving 18 patients receiving moclobemide and 16 patients receiving brofaromine. Patients were administered either moclobemide 200 mg b.i.d., mianserin 10 mg. t.i.d., and placebo (study 1), or brofaromine 50 and 75 mg b.i.d., doxepin 25 mg t.i.d., and placebo (study 2) for 8 consecutive days. A standardized driving test was conducted on day 1 and day 8 of treatment. Daily logs of estimated sleep duration and quality were obtained. Neither moclobemide nor brofaromine impaired driving performance. Some indication, although statistically not significant, was found that moclobemide improved driving performance on day 1. Brofaromine 75 mg significantly improved driving performance on day 8 of treatment. No significant difference between the effects of both drugs was found in a cross-study comparison. Moclobemide did not affect any sleep parameter, whereas brofaromine shortened sleep duration and decreased sleep quality. On day 1, mianserin and doxepin impaired driving. Impairment dissipated after 8 days of treatment with doxepine but not during treatment with mianserin. Sleep duration was prolonged during treatment with both drugs, whereas sleep quality remained unaffected. It is concluded that both MAO-A inhibitors are safe drugs with respect to driving.

Adult↗
PubMed1993

Seasonal allergic rhinitis and antihistamine effects on children's learning.

Children suffering from seasonal allergic rhinitis and matched normals were instructed on the use of a didactic computer simulation in a realistic classroom situation. Groups of atopic children received different treatments before instruction; ie, sedating (diphenylhydramine HCl) or nonsedating (loratadine) antihistamines or placebo. All returned after 2 weeks for an examination measuring factual and conceptual knowledge and the application of a learned strategy. Examination results showed large and consistent impairing effects of the allergic reaction on prior learning. Both the placebo and diphenhydramine groups learned significantly less than normal controls. The loratadine group's learning performance was superior to either of the other atopic groups' but still inferior to the normals'. Our conclusions are that the allergic reaction reduces learning ability in children and that this effect is partially counteracted by treatment with loratadine and aggravated by diphenhydramine.

Child↗
PubMed1992

Effects of loratadine and cetirizine on actual driving and psychometric test performance, and EEG during driving.

Sixteen healthy male and female volunteers took part in a 6-way, double-blind cross-over trial to compare the effects of single doses of cetirizine 10 mg, loratadine 10 mg and placebo, with and without alcohol (0.72 g.kg-1, lean body mass). Performance was measured in two repetitions of a psychometric test battery, and a standard, over-the-road driving test. EEG was also measured during driving. Alcohol significantly affected almost every performance measure and altered the EEG energy spectrum during driving whilst the blood concentrations declined from 0.37 to 0.20 mg.ml-1. The effects of cetirizine of on driving performance resembled those of alcohol. It caused the subjects to operate with significantly greater variability in speed and lateral position ('weaving' motion). The effects of alcohol and cetirizine appeared to be additive. Certain cetirizine-placebo differences in subjective feelings and test battery performance were also significant. Loratadine had no significant effect on any performance parameter. It was concluded that cetirizine, but not loratadine, generally caused mild impairment of performance after a single 10 mg dose.

Adult↗
PubMed1992

Effects of zolpidem and flunitrazepam on nocturnal sleep of women subjectively complaining of insomnia.

Eighteen non-pregnant woman complaining about insomnia were polysomnographically investigated for 3 nights with weekly intervals. They received placebo, 2 mg flunitrazepam or 10 mg zolpidem according to a cross-over double blind design. The patients were selected by general practitioners on the basis of subjective complaints. Zolpidem is a recently introduced short-acting imidazopyridine hypnotic, binding to a subunit of the benzodiazepine 1 receptor. Flunitrazepam is a well-known hypnotic, binding to both the benzodiazepine 1 and 2 receptor subtypes. Objective recording did not substantiate the subjective complaint of insomnia. Sleep patterns during placebo differed only little from that expected from age matched healthy persons. Both flunitrazepam and zolpidem significantly shortened sleep onset (5 min of continuous sleep beginning with NREM 1 sleep). The sleep composition following flunitrazepam was characterized by an increase in NREM 2, a prolongation of the time of REM sleep, a reduction of REM sleep and an increase in NREM 3-4 sleep during the first 2 h of sleep. The sleep composition following zolpidem resembled more than seen in persons without sleep complaints. However, as compared to placebo, there was a decrease of the time spent awake during sleep and an increase in NREM 3-4 during the first 2 of sleep.

Adult↗
PubMed1992

Effects of moclobemide and mianserin on highway driving, psychometric performance and subjective parameters, relative to placebo.

The acute and sub-chronic effects of moclobemide and mianserin on driving and psychometric performance were compared to those of placebo in a double-blind, cross-over study involving 17 healthy volunteers. Mianserin, moclobemide and placebo were administered for 8 days. Subjects' performance was measured on days 1 and 8 of each treatment series; subjective sleep parameters, mood, and possible side-effects were recorded each treatment day on questionnaires or visual analog scales. Mianserin affected most of the performance measures, while moclobemide affected none; mianserin also impaired driving and tracking performance and decreased CFF. Whilst receiving mianserin, subjects reported depressed levels of alertness, calmness, and contentment; the quality of their sleep was unaffected, but its duration increased, together with feelings of drowsiness and fatigue during the day. No statistical interactions between the factors Drugs and (Treatment) Days were found, indicating that little pharmacological tolerance developed over time during mianserin treatment. Mianserin's sedative properties are held responsible for all performance and subjective effects of the drug. It is concluded that moclobemide 200 mg b.i.d. has no important sedative properties.

Adult↗