Biomedical subjects

Ian Hindmarch

Publications and source records attributed to Ian Hindmarch.

24 records · Page 2Linked to original sources

PubMed2003

First do no harm: managing antihistamine impairment in patients with allergic rhinitis.

Antihistamines are effective medications that have been used for decades in the management of allergic rhinitis; however, they may be administered or selected in an inappropriate fashion and may be the source of drug-related morbidity. Our objective is to present relevant background information and an expert consensus statement on the use of antihistamines in treatment of allergic rhinitis. In July 2002, 14 experts in allergy, clinical immunology, pharmacology, and impairment assessment were invited to participate in a roundtable conference to present current concepts and develop a consensus statement on the clinical management of allergic rhinitis with antihistamines. Many of the antihistamines used to treat allergic rhinitis, as well as the disease itself, may produce sedation, impairment, and reduced quality of life. Allergic rhinitis is more appropriately managed with the relatively nonimpairing second-generation antihistamines (eg, loratadine, desloratadine, cetirizine, and fexofenadine), because older agents (eg, diphenhydramine, chlorpheniramine, and brompheniramine) produce sedation and impairment and worsen sleep architecture. Although there is some debate surrounding the varying degrees of efficacy of second-generation antihistamines, it is known that some agents may produce varying levels of drowsiness or impairment, especially at higher than recommended doses. The differences with regard to safety among the second-generation antihistamines are smaller than are the differences between the first and second generations. A nonsedating, nonimpairing (even at higher than recommended doses), second-generation antihistamine is preferred for all patients, particularly those with a higher risk for the development of adverse effects. We recommend that primary care and specialist physicians, nurse practitioners, physician assistants, pharmacists, and all other health professionals involved in the diagnosis and treatment of allergic rhinitis follow this consensus document and share this information with patients for whom antihistamine therapy is recommended. In addition, further epidemiologic studies on the effects of antihistamines should be performed.

Diagnosis, Differential↗

PubMed2003

Prediction of the rate of decline in cognitive function in Alzheimer's disease: a model based on simple demographic data and widely used rating scales.

Dementia represents a significant burden on the resources of both the National Health Service and Social Services as well as a great strain on the caregivers. The ability to predict, at diagnosis, those dementia patients that will deteriorate rapidly would allow a more effective allocation of resources as well as enabling the families and caregivers to make appropriate preparations. We performed discriminant analysis on a placebo data set of over 5,000 patients with Alzheimer's disease in order to create a model that predicts the rate of cognitive decline in Alzheimer's disease from simple demographic data and the baseline score on the cognitive subscale of the Alzheimer's Disease Assessment Scale or the Mini Mental State Examination. This model has 96-97% sensitivity and 92-93% specificity. The potential benefits of this model argue for its validation in a prospective study.

Adult↗

PubMed2001

Residual effects of zaleplon and zolpidem following middle of the night administration five hours to one hour before awakening.

The objective was to assess residual effects of zaleplon and zolpidem after a middle of the night administration. This was a randomized, double-blind, placebo-controlled, crossover study, conducted in 40 healthy young male and female subjects. Subjects were awakened in the middle of the night and administered either placebo or zaleplon 10 or 20 mg or zolpidem 10 mg. A battery of objective tests exploring psychomotor and cognitive functions such as critical flicker fusion (CFF), choice reáction time (CRT), digit symbol substitution test (DSST), and memory tests (Sternberg memory scanning and a word list) were administered immediately after morning waking. Zaleplon 10 mg was devoid of residual effects whatever - the time of dosing - except a minimal but significant decrease in DSST scores when administered 1 h before awakening. Zaleplon 20 mg produced significant residual effects on performance (increase in CRT, and decrease in CFF threshold and in DSST scores) and memory (decrease in immediate and delayed free recall of words) only when administered 1 h before awakening. In contrast, zolpidem 10 mg produced significant detrimental residual effects on CRT and delayed free recall of words, when administered up to 5 h before waking, on DSST and Sternberg when administered up to 3 h before awakening and on CFF when administered 1 h before awakening. The residual effects of zolpidem 10 mg were more marked than those observed after zaleplon 20 mg. The present results demonstrate that zaleplon 10 mg has no or minimal residual effects when administered in the middle of the night as little as 1 h before waking. The lack of clinically significant residual effects with zaleplon may be explained by its unique pharmacokinetic (rapid elimination half-life) and pharmacodynamic (selective binding for GABA(A) receptors with the alpha(1) subunit, dissociation between sleep inducing properties and impairment of cognitive functions) profiles. Copyright 2001 John Wiley & Sons, Ltd.

Journal Article↗

PubMed2001

Pharmacodynamic profile of Zaleplon, a new non-benzodiazepine hypnotic agent.

The challenge in developing hypnotic agents for the treatment of insomnia is to balance the sedative effect needed at bedtime with the residual sedation on awakening. Zaleplon is a novel pyrazolopyrimidine hypnotic agent that acts as a selective agonist to the brain omega(1) receptor situated on the alpha(1) subunit of the GABA(A) receptor complex. Zaleplon was proven to be an effective hypnotic drug as it consistently and significantly reduced latency to persistent sleep in insomniac patients for doses of 10 mg and above in polysomnography studies. The pharmacodynamic profile of zaleplon on psychomotor performance, actual driving and cognitive function, including memory, was assessed in several randomized, double-blind, placebo-controlled studies in healthy young subjects as well as insomniac patients by using various positive controls (zolpidem, zopiclone, triazolam and flurazepam). The recommended hypnotic dose of zaleplon in young adults (10 mg) produced minimal or no impairment of psychomotor and memory performance even when administered during the night as little as 1 h before waking. No impairment of actual driving was observed when zaleplon 10 mg was administered either at bedtime or in the middle of the night as little as 4 h before waking. Zaleplon 20 mg, twice the recommended dose, generally produced significant impairment of performance and cognitive functions when these functions were measured at the time of peak plasma concentration, i.e. 1 h after dose administration, and no impairment of driving abilities was observed 4 h after a middle-of-the-night administration. In contrast, consistent detrimental residual effects on various aspects of psychomotor and cognitive functions were observed with the therapeutic doses of the various commonly prescribed hypnotic agents used as comparators, e.g. zolpidem 10 mg up to 5 h after dose administration, zopiclone 7.5 mg up to 10 h after, flurazepam 30 mg up to 14 h after and triazolam 0.25 mg up to 6 h after. Also, zolpidem 10 mg and zopiclone 7.5 mg were also shown to significantly impair driving ability the next morning when this was measured 4 h and up to 10 h after dose administration, respectively. The present review shows that zaleplon 10 mg has little or no residual effect when administered in the middle of the night, as late as 1 h before waking, and is devoid of impairment of driving abilities as assessed by actual driving 4 h after dose administration. The lack of clinically significant or minimally statistically significant residual effects of zaleplon even at its peak concentration may be explained by its unique pharmacokinetic (rapid elimination half-life) and pharmacodynamic (low affinity, and specific binding profile to various subunits of the GABA(A)receptor) profiles. These properties allow zaleplon to be used for treatment of symptoms only when they occur, either at bedtime or later in the night, without incurring significant risk of developing next-day impairment of psychomotor and cognitive functioning. Copyright 2001 John Wiley & Sons, Ltd.

Journal Article↗

PubMed2001

The enantiomer debate: current status and future directions.

Psychopharmacology, and the treatment of depression in particular, is one area where there is currently an increasing awareness of chiral drug phenomena. It is now generally agreed that the pharmacological and pharmacokinetic properties of chiral drugs and their enantiomers should be assessed early on in the drug development process. However, issues surrounding the potential advantages and disadvantages of enantiomeric drugs, compared with racemates, continue to be debated. This article highlights some of the key issues raised during one such debate, the aim of which was to address the hypothesis that each enantiomeric drug should be considered on its own merit. The idea is considered both in general terms and specifically in the context of clinical psychiatry, with an emphasis on the treatment of depression. An update on recent developments in enantiomeric antidepressant therapy is also provided. Copyright 2001 John Wiley & Sons, Ltd.

Journal Article↗

PubMedDate not supplied

The effects of carbon dioxide in champagne on psychometric performance and blood-alcohol concentration.

AIMS: To assess the effects of carbon dioxide (CO(2)) in champagne on psychomotor performance and blood-alcohol concentration (BAC). METHODS: Twelve subjects consumed ethanol (0.6 g/kg body weight) served as champagne or champagne with the CO(2) removed, in a crossover study. RESULTS: Champagne produced significantly greater BACs and significantly increased reaction times in a divided attention task, than degassed champagne. CONCLUSIONS: The CO(2) in champagne may accelerate absorption of alcohol, leading to more rapid or severe intoxication.

Alcohol Drinking↗